WorldWideScience

Sample records for interleukin-6 trans-signalling differentially

  1. INTERLEUKIN-6 TRANS-SIGNALING SYSTEM IN INTRA-AMNIOTIC INFLAMMATION, PRETERM BIRTH AND PRETERM PREMATURE RUPTURE OF THE MEMBRANES

    Science.gov (United States)

    Lee, Sarah Y.; Buhimschi, Irina A.; Dulay, Antonette T.; Ali, Unzila A.; Zhao, Guomao; Abdel-Razeq, Sonya S.; Bahtiyar, Mert O.; Thung, Stephen F.; Funai, Edmund F.; Buhimschi, Catalin S.

    2013-01-01

    Classic IL-6 signaling is conditioned by the transmembrane receptor (IL-6R) and homodimerization of gp130. During trans-signaling, IL-6 binds to soluble IL-6R (sIL-6R) enabling activation of cells expressing solely gp130. Soluble gp130 (sgp130) selectively inhibits IL-6 trans-signaling. To characterize amniotic fluid IL-6 trans-signaling molecules (IL-6, sIL-6R, sgp130) in normal gestations and pregnancies complicated by intra-amniotic inflammation (IAI) we studied 301 women during second trimester (n=39), third trimester (n=40) and preterm labor with intact (n=131, 85 IAI negative & 46 IAI positive) or preterm premature rupture of membranes (PPROM: n=91, 61 IAI negative & 30 IAI positive). ELISA, Western blotting and RT-PCR were used to investigate amniotic fluid, placenta and amniochorion for protein and mRNA expression of sIL-6R, sgp130, IL-6R and gp130. Tissues were immunostained for IL-6R, gp130, CD15+ (polymorphonuclear) and CD3+ (T-cell) inflammatory cells. The ability of sIL-6R and sgp130 to modulate basal and LPS-stimulated release of amniochorion matrix-metalloprotease-9 (MMP-9) was tested ex-vivo. We showed that in physiologic gestations amniotic fluid sgp130 decreases toward term. Amniotic fluid IL-6 and sIL-6R were elevated in IAI whereas sgp130 was decreased in PPROM. Our results suggested that fetal membranes are the probable source of amniotic fluid sIL-6R and sgp130. Immunohistochemistry and RT-PCR revealed increased IL-6R and decreased gp130 expression in amniochorion of women with IAI. Ex-vivo, sIL-6R and LPS augmented amniochorion MMP-9 release whereas sgp130 opposed this effect. We conclude that IL-6 trans-signaling molecules are physiologic constituents of the amniotic fluid regulated by gestational age and inflammation. PPROM likely involves functional loss of sgp130. PMID:21282511

  2. Interleukin-6 trans-signaling increases the expression of carcinoembryonic antigen-related cell adhesion molecules 5 and 6 in colorectal cancer cells.

    Science.gov (United States)

    Holmer, Reinhild; Wätzig, Georg H; Tiwari, Sanjay; Rose-John, Stefan; Kalthoff, Holger

    2015-12-16

    Colorectal cancer (CRC) is among the five most frequent causes for cancer-related deaths in Europe. One of the most important tumor-associated antigens for CRC is carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), which is involved in cell adhesion, migration, anoikis, tumor invasion and metastasis. Its family member CEACAM6 is also upregulated in adenomas and carcinomas of the colon and an independent predictor of poor survival. Previous studies have reported a link between upregulation of CEACAM5 and interleukin-6 (IL-6). IL-6 plays an important role in CRC progression, and signaling is mediated via two pathways (classic and trans-signaling). However, this link could not be confirmed by other studies, and the role of IL-6 trans-signaling in the CEACAM5 upregulation has not been elucidated. Moreover, the impact of IL-6 on the expression of CEACAM6 has not yet been examined. The expression of IL-6, IL-6 receptor (IL-6R), glycoprotein (gp) 130, CEACAM5 and CEACAM6 was analyzed by RT-PCR, Western blot, flow cytometry or qPCR. Colon cell lines were incubated with IL-6 or Hyper-IL-6 (mediating IL-6 trans-signaling), and subsequently, the expression of CEACAMs was determined by qPCR or Western blot. FLLL31, an inhibitor of the phosphorylation of signal transducer and activator of transcription-3 (STAT3), was used to determine the role of STAT3 phosphorylation. We confirmed that colon carcinoma cell lines express IL-6 and IL-6R. We observed only a weak upregulation of CEACAM5 and CEACAM6 by classic IL-6 signaling, but a strong increase by IL-6 trans-signaling. This upregulation depended on the phosphorylation of STAT3. Our data show the upregulation of the tumor-associated antigens CEACAM5/6 by trans-signaling of the pro-inflammatory cytokine IL-6. This mechanism may contribute to the tumor-promoting role of IL-6 and could therefore be a target for therapeutic intervention in particular by specific inhibitors such as sgp130Fc.

  3. Induction of NFATc2 expression by interleukin 6 promotes T helper type 2 differentiation.

    Science.gov (United States)

    Diehl, Sean; Chow, Chi-Wing; Weiss, Linda; Palmetshofer, Alois; Twardzik, Thomas; Rounds, Laura; Serfling, Edgar; Davis, Roger J; Anguita, Juan; Rincón, Mercedes

    2002-07-01

    Interleukin (IL)-6 is produced by professional antigen-presenting cells (APCs) such as B cells, macrophages, and dendritic cells. It has been previously shown that APC-derived IL-6 promotes the differentiation of naive CD4+ T cells into effector T helper type 2 (Th2) cells. Here, we have studied the molecular mechanism for IL-6-mediated Th2 differentiation. During the activation of CD4+ T cells, IL-6 induces the production of IL-4, which promotes the differentiation of these cells into effector Th2 cells. Regulation of IL-4 gene expression by IL-6 is mediated by nuclear factor of activated T cells (NFAT), as inhibition of NFAT prevents IL-6-driven IL-4 production and Th2 differentiation. IL-6 upregulates NFAT transcriptional activity by increasing the levels of NFATc2. The ability of IL-6 to promote Th2 differentiation is impaired in CD4+ T cells that lack NFATc2, demonstrating that NFATc2 is required for regulation of IL-4 gene expression by IL-6. Regulation of NFATc2 expression and NFAT transcriptional activity represents a novel pathway by which IL-6 can modulate gene expression.

  4. Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells.

    Science.gov (United States)

    McCormick, C; Freshney, R I; Speirs, V

    1995-02-01

    The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified.

  5. Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening.

    Directory of Open Access Journals (Sweden)

    Thomas M Randau

    Full Text Available The preoperative differentiation between septic and aseptic loosening after total hip or knee arthroplasty is essential for successful therapy and relies in part on biomarkers. The objective of this study was to assess synovial and serum levels of inflammatory proteins as diagnostic tool for periprosthetic joint infection and compare their accuracy with standard tests. 120 patients presenting with a painful knee or hip endoprosthesis for surgical revision were included in this prospective trial. Blood samples and samples of intraoperatively acquired joint fluid aspirate were collected. White blood cell count, C-reactive protein, procalcitonin and interleukin-6 were determined. The joint aspirate was analyzed for total leukocyte count and IL-6. The definite diagnosis of PJI was determined on the basis of purulent synovial fluid, histopathology and microbiology. IL-6 in serum showed significantly higher values in the PJI group as compared to aseptic loosening and control, with specificity at 58.3% and a sensitivity of 79.5% at a cut-off value of 2.6 pg/ml. With a cut-off >6.6 pg/ml, the specificity increased to 88.3%. IL-6 in joint aspirate had, at a cut-off of >2100 pg/ml, a specificity of 85.7% and sensitivity of 59.4%. At levels >9000 pg/ml, specificity was almost at 100% with sensitivity just below 50%, so PJI could be considered proven with IL-6 levels above this threshold. Our data supports the published results on IL-6 as a biomarker in PJI. In our large prospective cohort of revision arthroplasty patients, the use of IL-6 in synovial fluid appears to be a more accurate marker than either the white blood cell count or the C-reactive protein level in serum for the detection of periprosthetic joint infection. On the basis of the results we recommend the use of the synovial fluid biomarker IL-6 for the diagnosis of periprosthetic joint infection following total hip and knee arthroplasty.

  6. Relationship between Interleukin-6 gene polymorphism and hippocampal volume in antipsychotic-naïve schizophrenia: evidence for differential susceptibility?

    Directory of Open Access Journals (Sweden)

    Sunil Vasu Kalmady

    Full Text Available Various lines of evidence including epidemiological, genetic and foetal pathogenetic models suggest a compelling role for Interleukin-6 (IL-6 in the pathogenesis of schizophrenia. IL-6 mediated inflammatory response triggered by maternal infection or stress induces disruption of prenatal hippocampal development which might contribute towards psychopathology during adulthood. There is a substantial lack of knowledge on how genetic predisposition to elevated IL-6 expression effects hippocampal structure in schizophrenia patients. In this first-time study, we evaluated the relationship between functional polymorphism rs1800795 of IL-6 and hippocampal gray matter volume in antipsychotic-naïve schizophrenia patients in comparison with healthy controls.We examined antipsychotic-naïve schizophrenia patients [N = 28] in comparison with healthy controls [N = 37] group matched on age, sex and handedness. Using 3 Tesla - MRI, bilateral hippocampi were manually segmented by blinded raters with good inter-rater reliability using a valid method. Additionally, Voxel-based Morphometry (VBM analysis was performed using hippocampal mask. The IL-6 level was measured in blood plasma using ELISA technique. SNP rs1800795 was genotyped using PCR and DNA sequencing. Psychotic symptoms were assessed using Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms.Schizophrenia patients had significantly deficient left and right hippocampal volumes after controlling for the potential confounding effects of age, sex and total brain volume. Plasma IL-6 levels were significantly higher in patients than controls. There was a significant diagnosis by rs1800795 genotype interaction involving both right and left hippocampal volumes. Interestingly, this effect was significant only in men but not in women.Our first time observations suggest a significant relationship between IL-6 rs1800795 and reduced hippocampal volume in antipsychotic

  7. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

    2012-01-01

    Interleukin-6 (IL-6) is a pleiotropic immunomodulatory cytokine produced by various types of cells, including melanoma cells. IL-6 plays a major role in the pathogenesis and development of malignancies. It promotes tumour growth by inhibition of apoptosis and induces tumour angiogenesis. IL-6...

  8. Interleukin-6: a bone marrow stromal cell paracrine signal that induces neuroendocrine differentiation and modulates autophagy in bone metastatic PCa cells.

    Science.gov (United States)

    Delk, Nikki A; Farach-Carson, Mary C

    2012-04-01

    Autophagy reallocates nutrients and clears normal cells of damaged proteins and organelles. In the context of metastatic disease, invading cancer cells hijack autophagic processes to survive and adapt in the host microenvironment. We sought to understand how autophagy is regulated in the metastatic niche for prostate cancer (PCa) cells where bone marrow stromal cell (BMSC) paracrine signaling induces PCa neuroendocrine differentiation (NED). In PCa, this transdifferentiation of metastatic PCa cells to neuronal-like cells correlates with advanced disease. Because autophagy provides a survival advantage for cancer cells and promotes cell differentiation, we hypothesized that autophagy mediates PCa NED in the bone. Thus, we determined the ability of paracrine factors in conditioned media (CM) from two separate BMSC subtypes, HS5 and HS27a, to induce autophagy in C4-2 and C4-2B bone metastatic PCa cells by characterizing the autophagy marker, LC3. Unlike HS27a CM, HS5 CM induced LC3 accumulation in PCa cells, suggesting autophagy was induced and indicating that HS5 and HS27a secrete a different milieu of paracrine factors that influence PCa autophagy. We identified interleukin-6 (IL-6), a cytokine more highly expressed in HS5 cells than in HS27a cells, as a paracrine factor that regulates PCa autophagy. Pharmacological inhibition of STAT3 activity did not attenuate LC3 accumulation, implying that IL-6 regulates NED and autophagy through different pathways. Finally, chloroquine inhibition of autophagic flux blocked PCa NED; hence autophagic flux maintains NED. Our studies imply that autophagy is cytoprotective for PCa cells in the bone, thus targeting autophagy is a potential therapeutic strategy.

  9. Differential Expression of the Activator Protein 1 Transcription Factor Regulates Interleukin-1ß Induction of Interleukin 6 in the Developing Enterocyte.

    Directory of Open Access Journals (Sweden)

    Catherine M Cahill

    Full Text Available The innate immune response is characterized by activation of transcription factors, nuclear factor kappa B and activator protein-1 and their downstream targets, the pro-inflammatory cytokines including interleukin 1β and interleukin 6. Normal development of this response in the intestine is critical to survival of the human neonate and delays can cause the onset of devastating inflammatory diseases such as necrotizing enterocolitis. Previous studies have addressed the role of nuclear factor kappa B in the development of the innate immune response in the enterocyte, however despite its central role in the control of multiple pro-inflammatory cytokine genes, little is known on the role of Activator Protein 1 in this response in the enterocyte. Here we show that the canonical Activator Protein 1 members, cJun and cFos and their upstream kinases JNK and p38 play an essential role in the regulation of interleukin 6 in the immature enterocyte. Our data supports a model whereby the cFos/cJun heterodimer and the more potent cJun homodimer downstream of JNK are replaced by less efficient JunD containing dimers, contributing to the decreased responsiveness to interleukin 1β and decreased interleukin 6 secretion observed in the mature enterocyte. The tissue specific expression of JunB in colonocytes and colon derived tissues together with its ability to repress Interleukin-1β induction of an Interleukin-6 gene reporter in the NCM-460 colonocyte suggests that induction of JunB containing dimers may offer an attractive therapeutic strategy for the control of IL-6 secretion during inflammatory episodes in this area of the intestine.

  10. Valor pronóstico y discriminatorio de la interleucina-6 y la proteína C-reactiva en la meningitis Interleukin-6 and C-reactive protein and its prognosis and differentiation value in meningitis

    Directory of Open Access Journals (Sweden)

    Amauri Noda Albelo

    2009-06-01

    sistema nervioso central en la meningitis bacteriana.INTRODUCTION: Meningitis is characterized by a marked inflammatory response in subarachnoid space, accompanied by the intrathecal production of many mediators including cytokines as á-tumor necrosis factor, â-interleukin-1 and interleukin-6. The aim of present paper was to estimate the concentration of interleukin-6 and C-reactive protein in the cerebrospinal fluid (CSF, and in serum from meningitis patients; to determine the possible relation among these concentrations, and meningitis etiology, and to set if there is an association among these variables and hospital stay. METHODS: A sample of 18 patients presenting with meningitis was selected: 6 patients diagnosed with meningitis of bacterial origin and 12 patients diagnosed with aseptic meningitis. In both groups we quantified interleukin-6 and C-reactive protein in CSF and in serum, as well as cytology and proteins in CSF. RESULTS: Concentrations of interleukin-6 in CSF in bacterial meningitis were higher than those of serum from these patients, and than those of CSF and serum from aseptic meningitis patients. C-reactive protein reached figures higher in bacterial meningitis serum. Interleukin-6 concentration in CSF was directly correlated with hospital stay. CONCLUSIONS: Interleukin-6 in CSF and of C-reactive protein in serum may to contribute to the accuracy in differential diagnosis between aseptic meningitis and the bacterial one. Interleukin-6 concentration in CSF allows us to assess the significance of inflammatory process in the CNS in meningitis. The selectively high interleukin-6 concentration in CSF is a marker to compartmentalize the inflammatory response, and a potential damage indicator in CNS in bacterial meningitis.

  11. CD147/basigin limits lupus nephritis and Th17 cell differentiation in mice by inhibiting the interleukin-6/STAT-3 pathway.

    Science.gov (United States)

    Maeda, Kayaho; Kosugi, Tomoki; Sato, Waichi; Kojima, Hiroshi; Sato, Yuka; Kamimura, Daisuke; Kato, Noritoshi; Tsuboi, Naotake; Yuzawa, Yukio; Matsuo, Seiichi; Murakami, Masaaki; Maruyama, Shoichi; Kadomatsu, Kenji

    2015-05-01

    Interleukin-17 (IL-17)-producing T cells (Th17 cells) play critical roles in the pathogenesis of immune-related diseases, including systemic lupus erythematosus. However, the fundamental mechanism regulating Th17 cell differentiation is not fully understood. Recently, we demonstrated that plasma levels of CD147/basigin (Bsg) in patients with lupus nephritis (LN) were closely associated with disease activity. but the molecular mechanism involving Bsg has been elusive. Here, we addressed the role of Bsg in the pathogenesis of LN. Injections of pristane (2,6,10,14-tetramethylpentadecane [TMPD]) were administered to Bsg(-/-) or Bsg(+/+) mice to induce LN. The mice were killed 6 months after being injected, for histologic and biochemical analyses of the kidneys and spleens. Pristane induced LN more strikingly in Bsg(-/-) mice than in Bsg(+/+) mice, even though humoral autoimmunity was similarly increased in both genotypes. The increased number of Th17, but not Th1, Treg cells, was augmented in Bsg(-/-) mice. The expression of IL-17 was also increased in the kidneys of Bsg(-/-) mice, in proportion to LN disease activity. Furthermore, treatment with anti-IL-17 antibody reduced LN disease activity in Bsg(-/-) mice. Complementary to these phenotypes of Bsg(-/-) mice, Bsg expression was enhanced in activated CD4+ T cells in vivo and in vitro. Bsg deficiency selectively augmented in vitro differentiation of naive CD4+ T cells to Th17 cells and STAT-3 phosphorylation during this differentiation. Moreover, STAT-3 phosphorylation was suppressed by crosslinking of Bsg with its antibody. Bsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL-6/STAT-3 pathway. © 2015, American College of Rheumatology.

  12. Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas.

    Science.gov (United States)

    Lee, Tin Lap; Yeh, Jason; Van Waes, Carter; Chen, Zhong

    2006-01-01

    Signal transducer and activator of transcription 3 (STAT3) has been reported to be activated by interleukin-6 receptor (IL-6R) or epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC), which may have important implications for responsiveness to therapeutics targeted at EGFR, IL-6R, or intermediary kinases. Suppressor of cytokine signaling-1 (SOCS-1) has been implicated recently in the negative regulation of IL-6R/Janus-activated kinase (JAK)-mediated activation of STAT3, suggesting that SOCS-1 could affect alternative activation of STAT3 by EGFR, IL-6R, and associated kinases. We investigated whether epigenetic modification of SOCS-1 affects STAT3 activation in response to IL-6R-, EGFR-, JAK-, or mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-mediated signal activation. STAT3 was predominantly activated by IL-6R via Jak1/Jak2 in HNSCC lines UMSCC-9 and UMSCC-38 in association with transcriptional silencing of SOCS-1 by hypermethylation. In UMSCC-11A cells with unmethylated SOCS-1, STAT3 activation was regulated by both EGFR and IL-6R via a JAK-independent pathway involving MEK. Pharmacologic inhibitors of JAK and MEK and expression of SOCS-1 following demethylation or transient transfection inhibited STAT3 activation and cell proliferation and induced cell apoptosis in corresponding cell lines. Hypermethylation of SOCS-1 was found in about one-third of human HNSCC tissues, making it a potentially relevant marker for STAT-targeted therapy in HNSCC patients. We conclude that SOCS-1 methylation status can differentially affect STAT3 activation by IL-6R and EGFR through JAK or MEK in different HNSCC and response to pharmacologic antagonists. Identifying the potential factors and the regulatory pathways in STAT3 activation has important implications for the development and selection of molecularly targeted therapy in HNSCC.

  13. Interleukin-6 Detection with a Plasmonic Chip

    Science.gov (United States)

    Tawa, Keiko; Sumiya, Masashi; Toma, Mana; Sasakawa, Chisato; Sujino, Takuma; Miyaki, Tatsuki; Nakazawa, Hikaru; Umetsu, Mitsuo

    Interleukin-6, a cytokine relating inflammatory and autoimmune activity, was detected with three fluorescence assays using a plasmonic chip. In their assays, the way of surface modification, sample volume, incubation time and mixing solution, were found to influence the detection sensitivity. When the assay was revised in the point of a rapid and easy process, the detection sensitivity was not compromised compared to assays with sufficient sample volume and assay time. To suit the purpose of immunosensing, the assay conditions should be determined.

  14. Triggered Urine Interleukin-6 Correlates to Severity of Symptoms in Nonfebrile Lower Urinary Tract Infections.

    Science.gov (United States)

    Sundén, Fredrik; Butler, Daniel; Wullt, Björn

    2017-07-01

    Objective diagnosis of symptomatic urinary tract infections in patients prone to asymptomatic bacteriuria is compromised by local host responses that are already present and the positive urine culture. We investigated interleukin-6 as a biomarker for nonfebrile urinary tract infection severity and diagnostic thresholds for interleukin-6 and 8, and neutrophils to differentiate between asymptomatic bacteriuria and urinary tract infection. Patients with residual urine and neurogenic bladders due to spinal lesions included in a long-term Escherichia coli 83972 asymptomatic bacteriuria inoculation trial were monitored for 2 years. Symptom scoring and urine sampling to estimate interleukin-6 and 8, and neutrophils were performed regularly monthly and at urinary tract infection episodes. Patients were followed in the complete study for a mean of 19 months (range 10 to 27) and those with asymptomatic bacteriuria with E. coli 83972 were followed a mean of 11 months (range 4 to 19). A total of 37 nonfebrile urinary tract infection episodes with complete data on interleukin-6 and 8, neutrophils and symptom scoring were documented. Interleukin-6 was the only marker that persistently increased during urinary tract infection compared to asymptomatic bacteriuria in pooled and paired intra-individual comparisons (p urinary tract infection symptoms (p urinary tract infection episodes. However, in urinary tract infections with worse symptoms interleukin-6 and neutrophils demonstrated equal good/excellent outcomes. Triggered interleukin-6 correlated to urinary tract infection symptom severity and demonstrated a promising differential diagnostic capacity to discriminate urinary tract infection from asymptomatic bacteriuria. Future studies should explore interleukin-6 as a biomarker of urinary tract infection severity and assess the treatment indication in nonfebrile urinary tract infections. Copyright © 2017 American Urological Association Education and Research, Inc. Published by

  15. Interleukin-6 in Allogeneic Stem Cell Transplantation: Its Possible Importance for Immunoregulation and As a Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Tor Henrik Anderson Tvedt

    2017-06-01

    Full Text Available Allogeneic stem cell transplantation is associated with a high risk of treatment-related mortality mainly caused by infections and graft-versus-host disease (GVHD. GVHD is characterized by severe immune dysregulation and impaired regeneration of different tissues, i.e., epithelial barriers and the liver. The balance between pro- and anti-inflammatory cytokine influences the risk of GVHD. Interleukin-6 (IL-6 is a cytokine that previously has been associated with pro-inflammatory effects. However, more recent evidence from various autoimmune diseases (e.g., inflammatory bowel disease, rheumatoid arthritis has shown that the IL-6 activity is more complex with important effects also on tissue homeostasis, regeneration, and metabolism. This review summarizes the current understanding of how pro-inflammatory IL-6 effects exerted during the peritransplant period shapes T-cell polarization with enhancement of Th17 differentiation and suppression of regulatory T cells, and in addition we also review and discuss the results from trials exploring non-selective IL-6 inhibition in prophylaxis and treatment of GVHD. Emerging evidence suggests that the molecular strategy for targeting of IL-6-initiated intracellular signaling is important for the effect on GVHD. It will therefore be important to further characterize the role of IL-6 in the pathogenesis of GVHD to clarify whether combined IL-6 inhibition of both trans- (i.e., binding of the soluble IL-6/IL-6 receptor complex to cell surface gp130 and cis-signaling (i.e., IL-6 ligation of the IL-6 receptor/gp130 complex or selective inhibition of trans-signaling should be tried in the prophylaxis and/or treatment of GVHD in allotransplant patients.

  16. Interleukin-6, age, and corpus callosum integrity.

    Directory of Open Access Journals (Sweden)

    Brianne M Bettcher

    Full Text Available The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6 and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine, as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC integrity, fractional anisotropy (FA of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories.

  17. Adrenaline influences the release of interleukin-6 from murine pituicytes

    DEFF Research Database (Denmark)

    Christensen, J D; Hansen, E W; Frederiksen, C

    1999-01-01

    In this study, we examined the effect of adrenaline and interleukin-1beta on interleukin-6 secretion from cultured murine neurohypophyseal cells. Cells were cultured from neurohypophyses of 3- to 5-week-old mice and experiments were performed after 13 days in culture. Interleukin-6 was measured...... in 24-h samples using a sandwich fluoroimmunoassay. Unstimulated cells released 19+/-3 fmol interleukin-6/neurohypophysis/24 h (mean +/- S.E.M., n = 42). Adrenaline and interleukin-1beta increased the release of interleukin-6 from the cells in a concentration-dependent manner. Incubation with adrenaline...

  18. Measurement of Interleukin-6 in Cerebrospinal Fluid for the Diagnosis of Bacterial Meningitis.

    Science.gov (United States)

    Dano, Ibrahim Dan; Sadou, Hassimi; Issaka, Bassira; Oukem-Boyer, Odile Ouwe Missi

    It is assessed whether the measurement of interleukin-6 in the cerebrospinal fluid can serve as a biomarker for the diagnosis of bacterial meningitis. Cerebrospinal fluid was obtained from 152 patients aged 0-15 years suspected of having meningitis. These patients were classified into the following groups: Bacterial meningitis (n = 85), aseptic meningitis (n = 35) and non-meningitis/control (n = 32) based on leukocyte count and bacterial identification by culture and molecular biology. Interleukin-6 concentrations in cerebrospinal fluid were measured by enzyme-linked immunosorbent assay. This study found a significant difference of the mean cerebrospinal fluid interleukin-6 level (p≤0.01) between patients with bacterial meningitis (3,538.69±2,560.78 pg mL -1) and patients with aseptic meningitis (332.51±470.69 pg mL -1) or those of the control group (205.83±79.39 pg mL -1). There was also a significant difference of the mean cerebrospinal fluid interleukin-6 level between patients with aseptic meningitis and those of the control group. Interleukin-6 had the highest area under the ROC curve: 0.94 (95% confidence interval: 0.901-0.979) compared to that of cerebrospinal fluid glucose and total protein. At a cut-off value of 1,065.96 pg mL -1, interleukin-6 had a sensitivity of 76.2% and specificity of 100%. Interleukin-6 is a potential biomarker for the differential diagnosis of meningitis.

  19. Regulation of interleukin-6 secretion in murine pituicytes

    DEFF Research Database (Denmark)

    Thorn, Anders; Tuxen, Mikkel; Moesby, Lise

    2005-01-01

    -gamma on interleukin-6 secretion was not affected by the specific inducible nitric oxide synthase inhibitor 1400W (N-(3-[aminomethyl]benzyl)acetamidine). Furthermore interferon-gamma dose dependently inhibits unstimulated interleukin-6 secretion. Use of the nitric oxide releaser DETA/NO (2,2'-(hydroxynitrosohydrazono...

  20. Raised Interleukin 6 Levels: A Risk Factor for Cardiovascular ...

    African Journals Online (AJOL)

    Raised Interleukin 6 Levels: A Risk Factor for Cardiovascular Associated Complications in HIV Positive Zambians before Initiation of Antiretroviral Therapy. P Nhhoma, T Kaile, G Kwenda, M Sinkala, F Mwaba, H. Mantina ...

  1. Interleukin-6 in cerebrospinal fluid as a biomarker of acute meningitis.

    Science.gov (United States)

    García-Hernández, Pablo; Prieto, Belén; Martínez-Morillo, Eduardo; Rodríguez, Verónica; Álvarez, Francisco V

    2016-01-01

    Microbiological culture of cerebrospinal fluid is the gold standard to differentiate between aseptic and bacterial meningitis, but this method has low sensitivity. A fast and reliable new marker would be of interest in clinical practice. Interleukin-6, secreted by T cells in response to meningeal pathogens and quickly delivered into cerebrospinal fluid, was evaluated as a marker of acute meningitis. A total of 150 cerebrospinal fluid samples were analysed by an electrochemiluminescence method, selected according to patient diagnosis: (a) bacterial meningitis confirmed by positive culture (n = 26); (b) bacterial meningitis with negative culture or not performed (n = 15); (c) viral meningitis confirmed by polymerase chain reaction or immunoglobulin G determination (n = 23); (d) viral meningitis with polymerase chain reaction negative or not performed (n = 42); and (e) controls (n = 44). Cerebrospinal fluid interleukin-6 concentration showed significant differences between all pathologic groups and the control group (P meningitis, interleukin-6 showed an area under the curve of 0.937 (95% confidence intervals: 0.895-0.978), significantly higher than those of classical biomarkers. An interleukin-6 cutoff of 1418 pg/mL showed 95.5% sensitivity and 77.5% specificity, whereas a value of 15,060 pg/mL showed 63.6% sensitivity and 96.7% specificity, for diagnosis of bacterial meningitis. Interleukin-6 measured by electrochemiluminescence method is a promising marker for early differentiation between aseptic and bacterial meningitis. More studies are needed to validate clinical implications for future practice in an emergency laboratory. © The Author(s) 2015.

  2. Serum YKL-40 and interleukin 6 levels in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Biggar, R.J.; Johansen, J.S.; Smedby, K.E.

    2008-01-01

    PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially...

  3. Interleukin-6, a new target for therapy in multiple myeloma?

    NARCIS (Netherlands)

    van Oers, M. H.; van Zaanen, H. C.; Lokhorst, H. M.

    1993-01-01

    During the past few years much insight has been gained into the immunobiology of multiple myeloma. It has become evident that the growth of myeloma cells is regulated by cytokines, notably interleukin-6. In this paper a brief review is given of the evidence derived from in vitro as well as in vivo

  4. Serotonin Transporter Gene, Depressive Symptoms, and Interleukin-6

    NARCIS (Netherlands)

    Su, Shaoyong; Zhao, Jinying; Bremner, J. Douglas; Miller, Andrew H.; Tang, Weining; Bouzyk, Mark; Snieder, Harold; Novik, Olga; Afzal, Nadeem; Goldberg, Jack; Vaccarino, Viola

    2009-01-01

    Background-We explored the relationship of genetic variants of the serotonin transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission, with both depressive symptoms and plasma interleukin-6 (IL-6) levels. Methods and Results-We genotyped 20 polymorphisms in 360 male twins (mean

  5. Metabolites associated with circulating interleukin-6 in older adults

    Science.gov (United States)

    Background: Circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) levels are elevated in older adults, but mechanisms are unclear. In the current study, we used an untargeted metabolomic approach to develop an improved understanding about mechanisms related to circulating IL-6 in ...

  6. Interleukin-6 receptor pathways in coronary heart disease

    DEFF Research Database (Denmark)

    Sarwar, Nadeem; Butterworth, Adam S; Freitag, Daniel F

    2012-01-01

    Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied...

  7. Interleukin 6, interleukin 1β, estradiol and testosterone ...

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... Key words: Oocyte maturation, follicular fluid, interleukin 6, interleukin 1β, testosterone, estradiol. INTRODUCTION. A complex of hormones, growth factors and cytokines regulates the ovarian function. The interaction between immune and endocrine systems is triggered by the action of immune cells within ...

  8. Analysis of interleukin-6 in endotoxin-induced uveitis

    NARCIS (Netherlands)

    Hoekzema, R.; Murray, P. I.; van Haren, M. A.; Helle, M.; Kijlstra, A.

    1991-01-01

    The mechanisms underlying the induction of intraocular inflammation in the rat model of endotoxin-induced uveitis (EIU) and the subsequent development of tolerance after repeated endotoxin injections are poorly understood. Interleukin-6 (IL-6) was measured in the aqueous humor and serum of Lewis

  9. Cellular and Oxidative Mechanisms Associated with Interleukin-6 Signaling in the Vasculature

    Directory of Open Access Journals (Sweden)

    Sean P. Didion

    2017-11-01

    Full Text Available Reactive oxygen species, particularly superoxide, promote endothelial dysfunction and alterations in vascular structure. It is increasingly recognized that inflammatory cytokines, such as interleukin-6 (IL-6, contribute to endothelial dysfunction and vascular hypertrophy and fibrosis. IL-6 is increased in a number of cardiovascular diseases, including hypertension. IL-6 is also associated with a higher incidence of future cardiovascular events and all-cause mortality. Both immune and vascular cells produce IL-6 in response to a number of stimuli, such as angiotensin II. The vasculature is responsive to IL-6 produced from vascular and non-vascular sources via classical IL-6 signaling involving a membrane-bound IL-6 receptor (IL-6R and membrane-bound gp130 via Jak/STAT as well as SHP2-dependent signaling pathways. IL-6 signaling is unique because it can also occur via a soluble IL-6 receptor (sIL-6R which allows for IL-6 signaling in tissues that do not normally express IL-6R through a process referred to as IL-6 trans-signaling. IL-6 signaling mediates a vast array of effects in the vascular wall, including endothelial activation, vascular permeability, immune cell recruitment, endothelial dysfunction, as well as vascular hypertrophy and fibrosis. Many of the effects of IL-6 on vascular function and structure are representative of loss or reductions in nitric oxide (NO bioavailability. IL-6 has direct effects on endothelial nitric oxide synthase activity and expression as well as increasing vascular superoxide, which rapidly inactivates NO thereby limiting NO bioavailability. The goal of this review is to highlight both the cellular and oxidative mechanisms associated with IL-6-signaling in the vascular wall in general, in hypertension, and in response to angiotensin II.

  10. [POEMS syndrome: role and value of interleukin-6].

    Science.gov (United States)

    Andrès, E; Courouau, F; Kaltenbach, G; Maloisel, F; Imler, M

    1996-01-01

    POEMS syndrome is a systemic disorder with peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. The association of POEMS syndrome with lympho-proliferative disorder is very commun. The pathogenesis remains poorly understood but implication of cytokines (interleukins 1 and 6) is suspected. We report a case of a classic POEMS syndrome (with polyneuropathy, hepatomegaly, diabetes melitus, hyperpigmentation, monoclonal IgG lambda, anasarca and solitary plasmocytoma), associated with high serum levels of interleukin 6.

  11. Muscular Interleukin-6 and Its Role as an Energy Sensor

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund

    2012-01-01

    muscle-liver and muscle-fat cross talk. The myokine prototype is interleukin-6 (IL-6). During exercise, contracting skeletal muscles release IL-6. It appears that IL-6 works as an energy sensor and exerts both local and endocrine metabolic effects. Given that skeletal muscle is the largest organ...... in the human body, the discovery of contracting muscle as a cytokine producing organ opens for a whole new paradigm: If the endocrine function of the muscle is not stimulated through contractions, it will cause malfunction of several organs and tissues of the body....

  12. Serum YKL-40 and interleukin 6 levels in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Biggar, R.J.; Johansen, J.S.; Smedby, K.E.

    2008-01-01

    PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially...... in nodular sclerosis Hodgkin lymphoma. EXPERIMENTAL DESIGN: We analyzed Danish and Swedish patients with incident Hodgkin lymphoma (N=470) and population controls from Denmark (n=245 for YKL-40; n=348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed...... by linear regression, adjusting for age and sex. RESULTS: Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold; both, PHodgkin lymphoma patients (n=176), levels were correlated...

  13. Aptamer conjugated silver nanoparticles for the detection of interleukin 6

    Science.gov (United States)

    Locke, Andrea K.; Norwood, Nicole; Marks, Haley L.; Schechinger, Monika; Jackson, George W.; Graham, Duncan; Coté, Gerard L.

    2016-03-01

    The controlled assembly of plasmonic nanoparticles by a molecular binding event has emerged as a simple yet sensitive methodology for protein detection. Metallic nanoparticles (NPs) coated with functionalized aptamers can be utilized as biosensors by monitoring changes in particle optical properties, such as the LSPR shift and enhancement of the SERS spectra, in the presence of a target protein. Herein we test this method using two modified aptamers selected for the protein biomarker interleukin 6, an indicator of the dengue fever virus and other diseases including certain types of cancers, diabetes, and even arthritis. IL6 works by inducing an immunological response within the body that can be either anti-inflammatory or pro-inflammatory. The results show that the average hydrodynamic diameter of the NPs as measured by Dynamic Light Scattering was ~42 nm. After conjugation of the aptamers, the peak absorbance of the AgNPs shifted from 404 to 408 nm indicating a surface modification of the NPs due to the presence of the aptamer. Lastly, preliminary results were obtained showing an increase in SERS intensity occurs when the IL-6 protein was introduced to the conjugate solution but the assay will still need to be optimized in order for it to be able to monitor varying concentration changes within and across the desired range.

  14. Salivary Interleukine 6 and its role on developing periodentitis

    Directory of Open Access Journals (Sweden)

    Thana Mohammed Juda

    2016-03-01

    Full Text Available Back ground Interleukin-6 (IL-6 is biologically active small protein molecules known as cytokines .These cytokines are produced by leukocytes, adipocytes, and endothelial cells, and it is involved mainly in inflammatory processes. IL-6 has a role in stimulating the immune response as trigger to infection or trauma through the production of acute-phase proteins that accompany the inflammatory process. IL-6 synthesized according to code from messenger RNA, so their production in tissue in responce of inflammation are increased by the action of increasing expression of its own specific messenger RNA and the expression levels of the mRNAs were either up- or down-regulated by adjacent focal infiltrating lymphoid cells according to the state of periodontal in health and disease so the local concentration of cytokines reflect the state of inflammatory process under control at nuclear level. The aim of study is to evaluate the inflammatory cytokine that associated the process of periodentitis Methods: Salivary specimens were obtained from patients having chronic periodentitis and healthy subject act as control group. The assessment of IL6 concentrations were established by technique enzyme linked immunoassay. . Results: level of IL-6 in saliva sample after evaluation the result showed statistically significant difference between patients and control . Conclusions: The result obtained from this study revealed that estimated salivary IL 6 can be used in management protocol of process of periodentitis

  15. Interleukin-6 blockade Improves Autonomic Dysfunction in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Ashit Syngle

    2015-01-01

    Full Text Available Autonomic nervous system (ANS involvement in rheumatoid arthritis (RA is well recognised and contributes to arrhythmia and sudden death. However, there is no study documented the therapeutic efficacy on autonomic neuropathy (AN in RA. This is the first reported observation of improvement in AN with interleukin-6 (IL-6 blockade with tocilizumab in RA. We report a case of 61-year old female with seropositive RA with severe disease activity, investigated for autonomic neuropathy. A battery of non invasive tests was used for accurate assessment of AN function based on assessment of peripheral sympathetic autonomic function and cardiovascular reflex tests. Tocilizumab 8mg/kg intravenous infusion at weeks 0, 4 and 8 was added to her treatment regimen. Cardiovascular autonomic function tests at baseline showed marked abnormalities of parasympathetic cardiovascular reflexes. After the first dose of tocilizumab there was a rapid improvement with normalization of parasympathetic autonomic activity with subsequent doses. IL-6 blockade with tocilizumab seems to have the potential to improve the vagus nerve mediated parasympathetic neuropathy and hence has the potential to restore cholinergic anti-inflammatory pathway.

  16. Interleukin-6 in Schizophrenia-Is There a Therapeutic Relevance?

    Science.gov (United States)

    Borovcanin, Milica Milovan; Jovanovic, Ivan; Radosavljevic, Gordana; Pantic, Jelena; Minic Janicijevic, Slavica; Arsenijevic, Nebojsa; Lukic, Miodrag L

    2017-01-01

    Renewing interest in immune aspects of schizophrenia and new findings about the brain-fat axis encourage us to discuss the possible role of interleukin-6 (IL-6) in schizophrenia. Previously, it was suggested that a primary alteration of the innate immune system may be relevant in schizophrenia. Functional dichotomy of IL-6 suggests that this chemical messenger may be responsible for regulating the balance between pro- and anti-inflammatory responses, with tissue-specific properties at the periphery and in the central nervous system. Specific phase of this chronic and deteriorating disorder must be considered, which can involve IL-6 in acute or possible chronic inflammation and/or autoimmunity. We give an overview of IL-6 role in the onset and progression of this disorder, also considering cognitive impairment and metabolic changes in patients with schizophrenia. Data suggest that decreased serum level of IL-6 following antipsychotic therapy could be predisposing factor for the development of obesity and obesity-related metabolic disorders in schizophrenia. As we reviewed, the IL-6 plays significant role in disease genesis and progression, so the use of specific inhibitors may not only be beneficial for exacerbation and alleviation of positive symptoms, but may attenuate cognitive impairment in patients with schizophrenia.

  17. Interleukin-6 in Schizophrenia—Is There a Therapeutic Relevance?

    Science.gov (United States)

    Borovcanin, Milica Milovan; Jovanovic, Ivan; Radosavljevic, Gordana; Pantic, Jelena; Minic Janicijevic, Slavica; Arsenijevic, Nebojsa; Lukic, Miodrag L.

    2017-01-01

    Renewing interest in immune aspects of schizophrenia and new findings about the brain-fat axis encourage us to discuss the possible role of interleukin-6 (IL-6) in schizophrenia. Previously, it was suggested that a primary alteration of the innate immune system may be relevant in schizophrenia. Functional dichotomy of IL-6 suggests that this chemical messenger may be responsible for regulating the balance between pro- and anti-inflammatory responses, with tissue-specific properties at the periphery and in the central nervous system. Specific phase of this chronic and deteriorating disorder must be considered, which can involve IL-6 in acute or possible chronic inflammation and/or autoimmunity. We give an overview of IL-6 role in the onset and progression of this disorder, also considering cognitive impairment and metabolic changes in patients with schizophrenia. Data suggest that decreased serum level of IL-6 following antipsychotic therapy could be predisposing factor for the development of obesity and obesity-related metabolic disorders in schizophrenia. As we reviewed, the IL-6 plays significant role in disease genesis and progression, so the use of specific inhibitors may not only be beneficial for exacerbation and alleviation of positive symptoms, but may attenuate cognitive impairment in patients with schizophrenia. PMID:29163240

  18. Usefulness of interleukin 6 levels in the cerebrospinal fluid for the diagnosis of bacterial meningitis.

    Science.gov (United States)

    Takahashi, Waka; Nakada, Taka-aki; Abe, Ryuzo; Tanaka, Kumiko; Matsumura, Yosuke; Oda, Shigeto

    2014-08-01

    Interleukin 6 (IL-6) is a proinflammatory cytokine produced during infections. We hypothesized that IL-6 levels in the cerebrospinal fluid (CSF) would be elevated in bacterial meningitis and useful for diagnosing and predicting neurologic outcomes. For the differentiation of bacterial meningitis, serum and CSF samples were obtained from patients with an altered level of consciousness. Patients were classified into 3 groups: bacterial meningitis, nonbacterial central nervous system disease, and other site sepsis. Of the 70 patients included in this study, there were 13 in the bacterial meningitis group, 21 in the nonbacterial central nervous system disease group, and 36 in the other site sepsis group. The CSF IL-6 level was significantly higher in the bacterial meningitis group than in the other 2 groups (Pbacterial meningitis. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Interleukin-6 genotypes and serum levels in Chinese Hui population.

    Science.gov (United States)

    Gao, Shu-Ping; Liang, Shu; Pan, Min; Sun, Rong-Liang; Chen, Chu; Luan, Hong; Jiang, Min-Hui

    2014-01-01

    Interleukin-6 (IL-6) is a key pro-inflammatory cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals. The Chinese Hui is one of the largest ethnic minorities, little is known about the distribution of IL-6 genetic variations and their effects on serum levels in Hui population. The aim of the present study is to determine the prevalence of -174G/C (rs1800795), -597G/A (rs1800797), and -634C/G (rs1800796) polymorphisms in the IL-6 gene promoter region and their association with IL-6 serum levels in the Ningxia Hui population. A total of 96 Hui subjects, (57 men and 39 women; mean age 49.65 ± 19.73 years) unrelated nationality residents in Ningxia Hui Autonomous Region were enrolled. Genotyping of the three polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis and then confirmed by direct sequencing. The -174G/C (97.92% GG, 2.08% GC, and 0% CC) and -597G/A (98.96% GG, 1.04% GA, and 0% AA) polymorphisms were rare. The frequencies of -634C/G genotypes CC, CG, and GG were found to be 54.17%, 40.62%, and 5.21%, respectively in total studied subjects, the derived allele frequencies for the C and G alleles were 74.48% and 25.52%. Increased IL-6 levels were correlated with the IL-6 -634G allele carriers (CG+GG genotypes). The results suggest that IL-6 -174G/C and -597G/A are rare but -634C/G is common in the Ningxia Hui population, and the -634G allele is associated with circulating levels of IL-6.

  20. Cyclosporin A Decreases Human Macrophage Interleukin-6 Synthesis at Post-Transcriptional Level

    Directory of Open Access Journals (Sweden)

    Juan E. Losa García

    1999-01-01

    Full Text Available In addition to its well-established effect on T cells, cyclosporin A (CsA also inhibits inflammatory cytokine production by macrophages. However, little is known about the mechanism of action of CsA on macrophage cytokine production. We measured the effect of CsA on basal and phorbol-myristate-acetate (PMA-stimulated production of interleukin-6 using the human monocyte cell line U937 differentiated with dimethylsulfoxide (DMSO. Interleukin-6 levels were measured in supernatant and cell lysates using specific enzyme-linked immunosorbent assays. We found that CsA decreases not only IL-6 release but also cytokine synthesis. The concentration of CsA used did not affect either cell viability or proliferation. Three possibilities may be advanced to explain the CsA-due decrease in IL-6 production by macrophages: (a inhibition of the synthesis of an early common regulatory protein, (b inhibition of cytokine gene transcription, or (c modulation of post-transcriptional events. The first possibility was tested by measuring the effect of cycloheximide on the experimental system during the first 3 hours of culture. Although cycloheximide decreased total cytokine synthesis, the pattern of cytokine modulation by CsA persisted. These data suggest that CsA-mediated macrophage cytokine inhibition is not mediated by an early common regulatory protein. To further explore the inhibition mechanism, we measured IL-6 mRNA levels by Northern blot. IL-6 mRNA levels were unaffected by CsA both in resting and PMA-stimulated cells. We conclude that in human macrophages CsA diminishes IL-6 production at post-transcriptional level.

  1. The ubiquitous interleukin-6: a time for reappraisal

    Directory of Open Access Journals (Sweden)

    Fisman Enrique Z

    2010-10-01

    Full Text Available Abstract Interleukin-6 (IL-6 is a multifunctional cytokine regulating humoral and cellular responses and playing a central role in inflammation and tissue injury. Its effects are mediated through interaction with its receptor complex, IL-6Rβ (also known as gp130. It plays an important role in the pathogenesis of coronary artery disease and large quantities of IL-6 are found in human atherosclerotic plaques. IL-6 levels positively correlate with higher all-cause mortality, unstable angina, left ventricular dysfunction, propensity to diabetes and its complications, hypertension, obesity and several types of cancer. IL-6 levels augmentation demonstrates a remarkable parallel with another biomarkers reflecting harmful processes, like tumor necrosis factor alpha, interleukins 8 and 18, YKL-40, C reactive protein and resistin. Due to these facts, IL-6 was classified as a noxious interleukin. Nonetheless, there are several facts that challenge this usually accepted point of view. Since IL-6 has also anti-inflammatory activity, it seems reasonable to assume that favorable aspects exist. These aspects are two: 1. protection against bacterial infections, inactivating proinflammatory mediators, mitigating the course of septic shock and inducing the production of cortisol; and 2. influence on insulin sensitivity during exercise; this aspect is even more important. During exercise IL-6 is synthesized and released by muscles, with enhanced insulin action immediately at early recovery. Skeletal muscle may be considered as an endocrine organ; contracting muscles produce IL-6 and release it into the blood exerting its effects on other organs. The increase in circulating levels of IL-6 after exercise is consistent and proportional to exercise duration, intensity, muscle mass involved and endurance capacity. Thus, the fascinating possibility that the plenteous beneficial health effects of exercise could be ultimately mediated by IL-6 merits further elucidation

  2. Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    T. Robak

    1998-01-01

    Full Text Available We investigated the serum concentrations of interleukin-6 (IL-6 and two IL-6 family of cytokines (leukaemia inhibitory factor (LIF and ciliary neurotrophic factor (CNTF as well as IL-6 soluble receptor (sIL-6R using an enzyme-linked immunosorbent assay (ELISA in 66 patients with rheumatoid arthritis (RA and 24 healthy controls. We examined a possible association between the serum levels of these peptides and RA activity according to the Mallya and Mace scoring system and Ritchie's index. We also evaluated the correlation between the serum levels of IL-6, LIF, CNTF and sIL-6R and duration of the disease and calculated sIL-6R/IL-6 ratio in RA patients and in the control group. IL-6 and sIL-6R were detectable in all 66 patients with RA and 24 normal individuals. LIF was also found in the serum of all patients with RA and in 16 (66.7% normal individuals. In contrast CNTF was measurable only in 15 (22.7% patients with RA and 24 (33.3% normal individuals. The highest IL-6 and sIL-6R levels were found in the patients with Stages 3 and 4 of RA activity and the lowest in the control group. In contrast there were no statistically significant diferences between the LIF and CNTF levels in RA patients and normal individuals. We found positive correlation between IL-6 and sIL-6R concentrations and Ritchie's index and a lack of such correlation with LIF and CNTF. IL-6 serum level correlated positively with the disease duration, but sIL-6R, LIF and CNTF did not. Serum sIL-6R/IL-6 ratio was significantly lower in RA patients than in healthy controls. In conclusion, an increase in the serum levels of IL-6 and sIL-6R, but not LIF and CNTF concentrations, may be useful markers for RA activity.

  3. Interleukin-6 but not soluble adhesion molecules has short-term ...

    African Journals Online (AJOL)

    Interleukin-6 but not soluble adhesion molecules has short-term prognostic value on mortality in patients with acute ST-segment elevation myocardial infarction. ZX Fan, Q Hua, J Tan, J Gao, RK Liu, Z Yang ...

  4. Serum Interleukin-6 in Patients with Burning Mouth Syndrome and Relationship with Depression and Perceived Pain

    Directory of Open Access Journals (Sweden)

    Qianming Chen

    2007-01-01

    Conclusions. Serum interleukin-6 in patients with burning mouth syndrome is decreased and negatively correlated to chronic pain. Both psychological and neuropathic disorders might act as precipitating factors in BMS etiopathogenesis.

  5. Cerebrospinal fluid interleukin-6 in central nervous system inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Alexandre Wullschleger

    Full Text Available BACKGROUND: Interleukin (IL-6 is recognised as an important cytokine involved in inflammatory diseases of the central nervous system (CNS. OBJECTIVE: To perform a large retrospective study designed to test cerebrospinal fluid (CSF IL-6 levels in the context of neurological diseases, and evaluate its usefulness as a biomarker to help discriminate multiple sclerosis (MS from other inflammatory neurological diseases (OIND. PATIENTS AND METHODS: We analyzed 374 CSF samples for IL-6 using a quantitative enzyme-linked immunosorbent assay. Groups tested were composed of demyelinating diseases of the CNS (DD, n = 117, including relapsing-remitting MS (RRMS, n = 65, primary progressive MS (PPMS, n = 11, clinically isolated syndrome (CIS, n = 11, optic neuritis (ON, n = 30; idiopathic transverse myelitis (ITM, n = 10; other inflammatory neurological diseases (OIND, n = 35; and non-inflammatory neurological diseases (NIND, n = 212. Differences between groups were analysed using Kruskal-Wallis test and Mann-Whitney U-test. RESULTS: CSF IL-6 levels exceeded the positivity cut-off of 10 pg/ml in 18 (51.4% of the 35 OIND samples, but in only three (3.9% of the 76 MS samples collected. CSF IL-6 was negative for all NIND samples tested (0/212. IL-6 cut-off of 10 pg/ml offers 96% sensitivity to exclude MS. CONCLUSION: CSF IL-6 may help to differentiate MS from its major differential diagnosis group, OIND.

  6. Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells

    International Nuclear Information System (INIS)

    Brozek, Wolfgang; Bises, Giovanna; Fabjani, Gerhild; Cross, Heide S; Peterlik, Meinrad

    2008-01-01

    Many cancer cells produce interleukin-6 (IL-6), a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of IL-6 modulators, i.e. IL-1β, prostaglandin E 2 , 17β-estradiol, and 1,25-dihydroxyvitamin D 3 , on expression and synthesis of the cytokine at different stages of tumour progression. We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the IL-6 gene promoter. IL-6 mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml) to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10 -7 M) reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the IL-6 promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the IL-6 gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-myc proto-oncogene expression. These effects were inhibited by 10 -8 M 1,25-dihydroxyvitamin D 3 . In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally affected, if at all, by PGE 2 , 1,25-dihydroxyvitamin D

  7. Interleukin-6 and prostate cancer: Current developments and unsolved questions.

    Science.gov (United States)

    Culig, Zoran; Puhr, Martin

    2018-02-15

    Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models. Experimental therapies have been proposed in order to block the IL-6/STAT3 signaling pathway. In this context, the anti-IL-6 antibody siltuximab (CNTO 328) has been demonstrated to inhibit growth of prostate tumors in vitro and in vivo and delays progression towards castration resistance. However, clinically, the anti-IL-6 antibody was not successful as a monotherapy in phase II studies in patients with metastatic PCa. IL-6 is implicated in regulation of cellular stemness by increasing phosphorylation of STAT3. The cytokine has also a role in development of resistance to the non-steroidal anti-androgen enzalutamide. Endogenous inhibitors of IL-6 are suppressors of cytokine signaling and protein inhibitors of activated STAT. Although they inhibit signal transduction through STAT3, they may also exhibit anti-apoptotic effects. On the basis of complexity of IL-6 action in PCa, an individualized approach is needed to identify patients who will benefit from anti-IL-6 therapy in combination with standard treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Interleukin-6 and lung inflammation: evidence for a causative role in inducing respiratory system resistance increments.

    Science.gov (United States)

    Rubini, Alessandro

    2013-10-01

    Interleukin-6 is a multifunctional cytokine that has been shown to be increased in some pathological conditions involving the respiratory system such as those experimentally induced in animals or spontaneously occurring in humans. Experimental data demonstrating that interleukin-6 plays a significant role in commonly occurring respiratory system inflammatory diseases are reviewed here. Those diseases, i.e. asthma and chronic obstructive pulmonary disease, are characterised by mechanical derangements of the respiratory system, for the most part due to increased elastance and airway resistance. Recent findings showing that interleukin-6 has a causative role in determining an increase in airway resistance are reviewed. The end-inflation occlusion method was used to study the mechanical properties of the respiratory system before and after interleukin-6 administration. The cytokine was shown to induce significant, dose-dependent increments in both the resistive pressure dissipation due to frictional forces opposing the airflow in the airway (ohmic resistance) and the additional resistive pressure dissipation due to the visco-elastic properties of the system, i.e. stress relaxation (visco-elastic resistance). There were no alterations in respiratory system elastance. Even when administered to healthy mammals, interleukin-6 determines a significant effect on respiratory system resistance causing an increase in the mechanical work of breathing during inspiration. IL-6 hypothetically plays an active role in the pathogenesis of respiratory system diseases and the mechanisms that may be involved are discussed here.

  9. Phosphatidylinositol 3-Kinase and Protein Kinase C Contribute to the Inhibition by Interleukin 6 of Phosphoenolpyruvate Carboxykinase Gene Expression in Cultured Rat Hepatocytes

    DEFF Research Database (Denmark)

    Christ, Bruno; Yazici, Emine; Nath, Annegret

    2000-01-01

    Gluconeogenesis, hepatocytes, interleukin 6, liver, phosphoinositide 3-kinase, phosphoenolpyruvate carboxykinase......Gluconeogenesis, hepatocytes, interleukin 6, liver, phosphoinositide 3-kinase, phosphoenolpyruvate carboxykinase...

  10. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Masahiko Mihara

    2011-02-01

    .Keywords: interleukin-6, tocilizumab, efficacy, safety, mode of action

  11. Interleukin-6

    DEFF Research Database (Denmark)

    Reihmane, Dace; Dela, Flemming

    2014-01-01

    as anti-inflammatory properties of IL-6. Since the first report of acute exercise-induced increase in plasma IL-6 in the early 1990s, scientists have tried to elucidate the factors that influence the magnitude of change of plasma IL-6, as well as the possible biological roles of this cytokine. Evidence...

  12. Interleukin-6

    DEFF Research Database (Denmark)

    Andersen, Mette Bisgaard; Pingel, Jessica; Kjær, Michael

    2011-01-01

    Human connective tissue, e.g., tendon, responds dynamically to physical activity, with collagen synthesis being increased after both acute and prolonged exercise or training. Markers of collagen synthesis and degradation as well as concentration of several potential growth factors have been shown...

  13. S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma

    DEFF Research Database (Denmark)

    de Nully Brown, P; Jensen, P O; Diamant, Marcus

    1998-01-01

    The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S-ph...

  14. Induction of plasma interleukin-6 by circulating adrenaline in the rat

    NARCIS (Netherlands)

    DeRijk, R. H.; Boelen, A.; Tilders, F. J.; Berkenbosch, F.

    1994-01-01

    Adrenaline, which is secreted from the adrenal medulla during stress, is considered to be involved in the control of inflammation and immune responses. Therefore, we studied the effects of adrenaline on the plasma levels of one of the major pro-inflammatory cytokines, interleukin-6 (IL-6). Here we

  15. Synergistic inhibition of interleukin-6 production in adipose stem cells by tart cherry anthocyanins and atorvastatin

    Science.gov (United States)

    Studies have shown positive correlations between inflammatory cytokines such as interleukin-6 (IL-6) and the development of chronic diseases including cardiovascular disease by activating C-reactive prorein (CRP). Both atorvastatin calcium (lipitor) as well as flavonoid rich fruit such as tart cherr...

  16. Early Dynamics of P-selectin and Interleukin 6 Predicts Outcomes in Ischemic Stroke

    DEFF Research Database (Denmark)

    Pusch, Gabriella; Debrabant, Birgit; Molnar, Tihamer

    2015-01-01

    to poststroke infection, death, and functional outcome, and assessed the ability of the models to predict each outcome. RESULTS: Interleukin 6 (IL-6) levels and change of IL-6 concentrations by 72 hours correlated with the size of tissue damage indicated by S100B titers. Levels of IL-6 and P-selectin at 72...

  17. Increased Levels of YKL-40 and Interleukin 6 in Patients With Chronic Pancreatitis and Secondary Diabetes

    DEFF Research Database (Denmark)

    Hansen, Morten; Nielsen, Anders Rinnov; Vilsbøll, Tina

    2012-01-01

    Circulating levels of YKL-40 and interleukin 6 (IL-6) are elevated in patients with type 2 diabetes. We aimed to evaluate YKL-40 levels in patients with chronic pancreatitis (CP) with and without secondary diabetes mellitus (DM) to investigate whether elevated plasma YKL-40 could play a primary...

  18. Oral contraception does not alter typical post-exercise interleukin-6 and hepcidin levels in females

    NARCIS (Netherlands)

    Sim, M.; Dawson, B.; Landers, G.; Swinkels, D.W.; Tjalsma, H.; Yeap, B.B.; Trinder, D.; Peeling, P.

    2015-01-01

    OBJECTIVES: The post-exercise interleukin-6 (IL-6) and hepcidin response was investigated during the hormone-deplete and hormone-replete phases of an estradiol and progestogen regulated oral contraceptive cycle (OCC). DESIGN: Counterbalanced, repeated measures cross-over study. METHODS: Ten active

  19. Interleukin-6 and Delayed Onset Muscle Soreness Do Not Vary during the Menstrual Cycle

    Science.gov (United States)

    Chaffin, Morgan E.; Berg, Kris E.; Meendering, Jessica R.; Llewellyn, Tamra L.; French, Jeffrey A.; Davis, Jeremy E.

    2011-01-01

    The purpose of this study was to determine if a difference in interleukin-6 (IL-6) and delayed onset muscles soreness (DOMS) exists in two different phases of the menstrual cycle. Nine runners performed one 75-min high-intensity interval running session during the early follicular (EF) phase and once during the midluteal (ML) phase of the…

  20. Interleukin-6 and neopterin in renal transplant recipients: a longitudinal study

    NARCIS (Netherlands)

    Raasveld, M. H.; Bloemena, E.; Wilmink, J. M.; Surachno, S.; Schellekens, P. T.; ten Berge, R. J.

    1993-01-01

    Serum and urine interleukin-6 (IL-6) levels and serum neopterin/creatinine ratios were longitudinally studied in 86 renal transplant recipients until 4 months after transplantation. During acute rejection and acute tubular necrosis (ATN), serum and urine IL-6 levels were elevated compared to during

  1. Interleukin-6 in CAPD patients without peritonitis: relationship to the intrinsic permeability of the peritoneal membrane

    NARCIS (Netherlands)

    Zemel, D.; ten Berge, R. J.; Struijk, D. G.; Bloemena, E.; Koomen, G. C.; Krediet, R. T.

    1992-01-01

    We investigated whether day to day changes in the transport characteristics of the peritoneal membrane to macromolecules in patients treated with CAPD, were related to the levels of interleukin-6 (IL-6) in the effluent of an overnight dwell. Four stable CAPD patients without peritonitis collected

  2. Modulation of chronic excessive interleukin-6 production in multiple myeloma does not affect thyroid hormone concentrations

    NARCIS (Netherlands)

    van Zaanen, H. C.; Romijn, J. A.; Sauerwein, H. P.; Lokhorst, H. M.; Warnaar, S. O.; Aarden, L. A.; Endert, E.; van Oers, M. H.

    1997-01-01

    Interleukin-6 (IL6) is believed to be involved in alterations of thyroid hormone metabolism in acute nonthyroidal illness. To evaluate the effects of IL6 on thyroid hormone metabolism in a chronic IL6-mediated disease, we measured thyroid hormone concentrations in multiple myeloma patients treated

  3. Serum interleukin-6 as a prognostic biomarker in patients with metastatic melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Johansen, Julia S

    2012-01-01

    Interleukin-6 (IL-6) is an immunomodulatory cytokine produced by both normal cells and tumor cells, including melanoma cells. The specific biological function of IL-6 in melanoma is unknown. The present study examined whether the serum concentration of IL-6 can predict prognosis in patients...

  4. Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Ogston, N. C.; Karastergiou, K.; Hosseinzadeh-Attar, M. J.; Bhome, R.; Madani, R.; Stables, M.; Gilroy, D.; Flachs, Pavel; Hensler, Michal; Kopecký, Jan; Mohamed-Ali, V.

    2008-01-01

    Roč. 32, č. 12 (2008), s. 1807-1815 ISSN 0307-0565 Grant - others:Wellcome trust(XE) 070821/Z/03/Z; EC(XE) LSHM-CT-2004-005272 Institutional research plan: CEZ:AV0Z50110509 Keywords : interleukin-6 * adipose tissue * aspirin Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.640, year: 2008

  5. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies

    NARCIS (Netherlands)

    Sarwar, Nadeem; Butterworth, Adam S.; Freitag, Daniel F.; Gregson, John; Willeit, Peter; Gorman, Donal N.; Gao, Pei; Saleheen, Danish; Rendon, Augusto; Nelson, Christopher P.; Braund, Peter S.; Hall, Alistair S.; Chasman, Daniel I.; Tybjærg-Hansen, Anne; Chambers, John C.; Benjamin, Emelia J.; Franks, Paul W.; Clarke, Robert; Wilde, Arthur A. M.; Trip, Mieke D.; Steri, Maristella; Witteman, Jacqueline C. M.; Qi, Lu; van der Schoot, C. Ellen; de Faire, Ulf; Erdmann, Jeanette; Stringham, Heather M.; Koenig, Wolfgang; Rader, Daniel J.; Melzer, David; Reich, David; Psaty, Bruce M.; Kleber, Marcus E.; Panagiotakos, Demosthenes B.; Willeit, Johann; Wennberg, Patrik; Woodward, Mark; Adamovic, Svetlana; Rimm, Eric B.; Meade, Tom W.; Gillum, Richard F.; Shaffer, Jonathan A.; Hofman, Albert; Onat, Altan; Sundström, Johan; Wassertheil-Smoller, Sylvia; Mellström, Dan; Gallacher, John; Cushman, Mary; Tracy, Russell P.; Kauhanen, Jussi; Karlsson, Magnus; Salonen, Jukka T.; Wilhelmsen, Lars; Amouyel, Philippe; Cantin, Bernard; Best, Lyle G.; Ben-Shlomo, Yoav; Manson, JoAnn E.; Davey-Smith, George; de Bakker, Paul I. W.; O'Donnell, Christopher J.; Wilson, James F.; Wilson, Anthony G.; Assimes, Themistocles L.; Jansson, John-Olov; Ohlsson, Claes; Tivesten, Åsa; Ljunggren, Östen; Reilly, Muredach P.; Hamsten, Anders; Ingelsson, Erik; Cambien, Francois; Hung, Joseph; Thomas, G. Neil; Boehnke, Michael; Schunkert, Heribert; Asselbergs, Folkert W.; Kastelein, John J. P.; Gudnason, Vilmundur; Salomaa, Veikko; Harris, Tamara B.; Kooner, Jaspal S.; Allin, Kristine H.; Nordestgaard, Børge G.; Hopewell, Jemma C.; Goodall, Alison H.; Ridker, Paul M.; Hólm, Hilma; Watkins, Hugh; Ouwehand, Willem H.; Samani, Nilesh J.; Kaptoge, Stephen; Di Angelantonio, Emanuele; Harari, Olivier; Danesh, John; Quertermous, Thomas; Go, Alan S.; Hlatky, Mark A.; Knowles, Joshua W.; Smith, Albert V.; Chrysohoou, Christina; Pitsavos, Christos; Stefanadis, Christodoulos; Balmforth, Anthony J.; Thompson, John R.; Sivapalaratnam, Suthesh; Maiwald, Stephani; Basart, Hanneke; Motazacker, Mahdi; de Jong, Jonas S. S. G.; Dekker, Lucas R. C.; Tanck, Michael; Bezzina, Connie R.; Whincup, Peter H.; Morris, Richard W.; Wannamethee, S. Goya; Kiechl, Stefan; Yarnell, John W. G.; Lowe, Gordon; Rumley, Ann; Mukamal, Kenneth J.; Havulinna, Aki S.; Lokki, Marja-Liisa; Nieminen, Markku S.; Ripatti, Samuli; Sinisalo, Juha; McQuillan, Brendan M.; Beilby, John P.; Thompson, Peter L.; Thorleifsson, Guðmar; Thorgeirsson, Guðmundur; Thorsteinsdóttir, Unnur; Stefansson, Kari; Jula, Antti; Männistö, Satu; Perola, Markus; Tikkanen, Emmi; Boer, Jolanda M. A.; Onland-Moret, N. Charlott; van der Schouw, Yvonne T.; Verschuren, W. M. Monique; Jansson, Jan-Håkan; Dupuis, Josée; Fontes, João D.; Yin, Xiaoyan; Tuomilehto, Jaakko; Koenig, Inke R.; Nahrstaedt, Janja; Loley, Christina; Stark, Klaus; Willenborg, Christina; Hengstenberg, Christian; Schreiber, Stefan; Preuss, Michael; Barroso, Inês; Hallmans, Göran; Shungin, Dmitry; Cheng, Kar Keung; Lam, Tai Hing; Jiang, Chao Chiang; Pai, Jennifer; Collins, Rory; Parish, Sarah; Armitage, Jane; Jackson, Anne; Hveem, Kristian; Wiggins, Kerri L.; Heckbert, Susan R.; Smith, Nicholas L.; Bis, Joshua C.; Ferrucci, Luigi; Guralnik, Jack M.; Bandinelli, Stefania; Singleton, Andrew B.; Tuomainen, Tomi-Pekka; Kurl, Sudhir; Zhang, Weihua; Kooner, Angad S.; Das, Debashis; März, Winfried; Scharnagl, Hubert; Böhm, Bernhard O.; Winkelmann, Bernhard R.; Folsom, Aaron R.; Shea, Steven J.; Laakso, Markku; Kuusisto, Johanna; Baumert, Jens; Thorand, Barbara; Illig, Thomas; Meisinger, Christa; Rosengren, Annika; Karlsson, Magnus K.; Hu, Frank B.; Hankinson, Susan E.; Davidson, Karina W.; Fraser, Ross; Wild, Sarah; Campbell, Harry; Qasim, Atif; Qu, Liming; Li, Mingyao; Lind, Lars; Syvänen, Ann-Christine; Arveiler, Dominique; Farrall, Martin; Peden, John F.; Deloukas, Panos; Sheikh, Nasir; Rasheed, Asif; Dagenais, Gilles R.; Dehghan, Abbas; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Abecasis, Goncalo R.; Cucca, Francesco; Sanna, Serena; Uda, Manuela; Schlessinger, David; Sabater-Lleal, Maria; Silveira, Angela; Gigante, Bruna; Howard, Barbara V.; Basu, Samar; Rose, Lynda M.; Buring, Julie

    2012-01-01

    Background Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we

  6. RECOMBINANT HUMAN INTERLEUKIN-6 INDUCES A RAPID AND REVERSIBLE ANEMIA IN CANCER-PATIENTS

    NARCIS (Netherlands)

    NIEKEN, J; MULDER, NH; VELLENGA, E; LIMBURG, PC; PIERS, DA; DEVRIES, EGE

    1995-01-01

    Initial studies have shown that recombinant human interleukin-6 (rhIL-6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II

  7. Endotoxin-induced uveitis in the rat. The significance of intraocular interleukin-6

    NARCIS (Netherlands)

    Hoekzema, R.; Verhagen, C.; van Haren, M.; Kijlstra, A.

    1992-01-01

    The potential role of interleukin-6 (IL-6) was studied as an inflammatory mediator of endotoxin (or lipopolysaccharide [LPS])-induced uveitis (EIU) in the rat. In young Lewis rats, levels of intraocular IL-6, but not serum IL-6, correlated with the severity of uveitis and with aqueous humor protein

  8. The interleukin-6 receptor as a target for prevention of coronary heart disease : a mendelian randomisation analysis

    NARCIS (Netherlands)

    Swerdlow, Daniel I.; Holmes, Michael V.; Kuchenbaecker, Karoline B.; Engmann, Jorgen E. L.; Shah, Tina; Sofat, Reecha; Guo, Yiran; Chung, Christina; Peasey, Anne; Ster, Roman Pfi; Mooijaart, Simon P.; Ireland, Helen A.; Leusink, Maarten; Langenberg, Claudia; Li, KaWah; Palmen, Jutta; Howard, Philip; Cooper, Jackie A.; Drenos, Fotios; Hardy, John; Nalls, Michael A.; Li, Yun Rose; Lowe, Gordon; Stewart, Marlene; Bielinski, Suzette J.; Peto, Julian; Timpson, Nicholas J.; Gallacher, John; Dunlop, Malcolm; Houlston, Richard; Tomlinson, Ian; Tzoulaki, Ioanna; Luan, Jian'an; Boer, Jolanda M. A.; Forouhi, Nita G.; Onland-Moret, N. Charlotte; van der Schouw, Yvonne T.; Schnabel, Renate B.; Hubacek, Jaroslav A.; Kubinova, Ruzena; Baceviciene, Migle; Tamosiunas, Abdonas; Pajak, Andrzej; Topor-Madry, Roman; Malyutina, Sofi A.; Baldassarre, Damiano; Sennblad, Bengt; Tremoli, Elena; de Faire, Ulf; Ferrucci, Luigi; Bandenelli, Stefania; Tanaka, Toshiko; Meschia, James F.; Singleton, Andrew; Navis, Gerjan; Mateo Leach, Irene; Bakker, Stephan J. L.; Gansevoort, Ron T.; Ford, Ian; Epstein, Stephen E.; Burnett, Mary Susan; Devaney, Joe M.; Jukema, J. Wouter; Westendorp, Rudi G. J.; de Borst, Gert Jan; van der Graaf, Yolanda; de Jong, Pim A.; Maitland-van der Zee, Anke-Hilse; Klungel, Olaf H.; de Boer, Anthonius; Doevendans, Pieter A.; Stephens, Jeffrey W.; Eaton, Charles B.; Robinson, Jennifer G.; Manson, JoAnn E.; Fowkes, F. Gerry R.; Frayling, Timothy M.; Price, Jackie F.; Whincup, Peter H.; Morris, Richard W.; Lawlor, Debbie A.; Smith, George Davey; Ben-Shlomo, Yoav; Redline, Susan; Lange, Leslie A.; Kumari, Meena; Wareham, Nick J.; Verschuren, W. M. Monique; Benjamin, Emelia J.; Whittaker, John C.; Hamsten, Anders; Dudbridge, Frank; Delaney, J. A. Chris; Wong, Andrew; Kuh, Diana; Hardy, Rebecca; Castillo, Berta Almoguera; Connolly, John J.; van der Harst, Pim; Brunner, Eric J.; Marmot, Michael G.; Wassel, Christina L.; Humphries, Steve E.; Talmud, Philippa J.; Kivimaki, Mika; Asselbergs, Folkert W.; Voevoda, Mikhail; Bobak, Martin; Pikhart, Hynek; Wilson, James G.; Hakonarson, Hakon; Reiner, Alex P.; Keating, Brendan J.; Sattar, Naveed; Hingorani, Aroon D.; Casas, Juan Pablo

    2012-01-01

    Background A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation.

  9. Source and kinetics of interleukin-6 in humans during exercise demonstrated by a minimally invasive model

    DEFF Research Database (Denmark)

    Toft, Anders Dyhr; Falahati, Ali; Steensberg, Adam

    2011-01-01

    The objective of this study was to use a novel and non-invasive model to explore whether: (1) exercise-induced increases in systemic levels of interleukin-6 (IL-6) and other cytokines can be ascribed to local production in working muscle; and (2) how acute release of retained blood from an exerci......The objective of this study was to use a novel and non-invasive model to explore whether: (1) exercise-induced increases in systemic levels of interleukin-6 (IL-6) and other cytokines can be ascribed to local production in working muscle; and (2) how acute release of retained blood from...... was inhibited for 18 min by inflating a cuff around the thigh as proximally as possible immediately following exercise. On the control occasion venous outflow was not inhibited. Venous blood samples were collected from an arm vein at 2-min intervals after exercise. During inhibition of venous outflow from...

  10. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T; Carrasco, J

    1999-01-01

    and reactive astrocytes surrounding the lesion site. In addition, expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and metallothionein-I+II (MT-I+II) were increased in these cells, while the brain-specific MT-III was only moderately upregulated. In IL-6-/- mice, however, the response......Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory...... response in the brain following disruption of the blood-brain barrier (BBB), we examined the effects of a focal cryo injury to the fronto-parietal cortex in interleukin-6-deficient (IL-6-/-) and normal (IL-6+/+) mice. In IL-6+/+ mice, brain injury resulted in the appearance of brain macrophages...

  11. Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

    DEFF Research Database (Denmark)

    Penkowa, M; Molinero, A; Carrasco, J

    2001-01-01

    and were killed six days later. Morphological damage to the hippocampal field CA1-CA3 was seen after kainic acid treatment. Reactive astrogliosis and microgliosis were prominent in kainic acid-injected normal mice hippocampus, and clear signs of increased oxidative stress were evident. Thus......The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice......, and caused a significant mortality (62%) only in the latter mice, indicating that interleukin-6 deficiency increased the susceptibility to kainic acid-induced brain damage. To compare the histopathological damage caused to the brain, control and interleukin-6 null mice were administered 8.75mg/kg kainic acid...

  12. Interleukin 6 modulates acetylcholinesterase activity of brain neurons; Effet de l`interleukine 6 sur l`activite de l`acetylcholinesterase des neurones centraux

    Energy Technology Data Exchange (ETDEWEB)

    Clarencon, D.; Multon, E.; Galonnier, M.; Estrade, M.; Fournier, C.; Mathieu, J.; Mestries, J.C.; Testylier, G.; Fatome, M.

    1995-12-31

    Classically, radiation injuries results in a peripheral inflammatory process, and we have previously observed an early systemic interleukin 6 (IL-6) release following whole-body irradiation. Besides, we have demonstrated an early decrease of rat or primate brain acetylcholinesterase (AChE) activity a gamma exposure. The object of the present study is to find possible IL-6 systemic effects on the brain AChE activity. We show that, though intravenous (i.v.) or intra-cerebro-ventricular (ICV) injection of IL-6 can induce a drop in rat brain AChE activity, this cytokine induces only a slight decrease of the AChE release in cultured brain cells. (author). 3 refs.

  13. Interleukin 6 signaling regulates promyelocytic leukemia protein gene expression in human normal and cancer cells

    Czech Academy of Sciences Publication Activity Database

    Hubáčková, Soňa; Krejčíková, Kateřina; Bartek, Jiří; Hodný, Zdeněk

    2012-01-01

    Roč. 287, č. 32 (2012), s. 26702-26714 ISSN 0021-9258 R&D Projects: GA ČR GA204/08/1418 Grant - others:Novo Nordisk(DK) R153-A12997; EK(XE) 223575 Institutional support: RVO:68378050 Keywords : cancer tumor promoter * DNA-binding protein * protein phosphorylation * tyrosine protein kinase * interleukin-6 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.651, year: 2012

  14. Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study

    OpenAIRE

    Puzianowska-Ku?nicka, Monika; Owczarz, Magdalena; Wieczorowska-Tobis, Katarzyna; Nadrowski, Pawel; Chudek, Jerzy; Slusarczyk, Przemyslaw; Skalska, Anna; Jonas, Marta; Franek, Edward; Mossakowska, Malgorzata

    2016-01-01

    Background In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65?years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly. Results IL-6 and CRP levels syst...

  15. Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Charlotte; Keller, Pernille

    2003-01-01

    Interleukin-6 (IL-6) is produced by many different cell types. Human skeletal muscles produce and release high amounts of IL-6 during exercise; however, the cell source of origin in the muscle is not known. Therefore, we studied the protein expression of IL-6 by immunohistochemistry in human musc...... are the dominant cell source of exercise-induced release of IL-6 from working muscle....

  16. Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion

    DEFF Research Database (Denmark)

    Vozarova, B; Weyer, C; Hanson, K

    2001-01-01

    Plasma concentrations of interleukin-6 (IL-6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined w...... whether circulating plasma IL-6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes....

  17. Association of Gene Polymorphisms in Interleukin 6 in Infantile Bronchial Asthma.

    Science.gov (United States)

    Babusikova, Eva; Jurecekova, Jana; Jesenak, Milos; Evinova, Andrea

    2017-07-01

    The genetic background of bronchial asthma is complex, and it is likely that multiple genes contribute to its development both directly and through gene-gene interactions. Cytokines contribute to different aspects of asthma, as they determine the type, severity and outcomes of asthma pathogenesis. Allergic asthmatics undergoing an asthmatic attack exhibit significantly higher levels of pro-inflammatory cytokines, such as interleukins and chemokines. In recent years, cytokines and their receptors have been shown to be highly polymorphic, and this prompted us to investigate interleukin 6 promoter polymorphisms at position -174G/C (rs1800795) and at -572G/C (rs1800796) in relation to asthma in children. Interleukin 6 promoter polymorphisms were analyzed in bronchial asthma patients and healthy children using polymerase chain reaction-restriction fragment length polymorphism analysis. We observed a significant association between polymorphism at -174G/C and bronchial asthma (OR=3.4, 95% CI: 2.045-5.638, P10 -7 ). Interleukin 6 polymorphism is associated with bronchial asthma, particularly its atopic phenotype. Expression and secretion of interleukins in asthmatic patients may be affected by genetic polymorphisms, and could have a disease-modifying effect in the asthmatic airway and modify the therapeutic response. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrP(C)), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Cross, Janet V; Franco-Lira, Maricela; Aragón-Flores, Mariana; Kavanaugh, Michael; Torres-Jardón, Ricardo; Chao, Chih-Kai; Thompson, Charles; Chang, Jing; Zhu, Hongtu; D'Angiulli, Amedeo

    2013-01-01

    Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile of cytokines, chemokines (Multiplexing LASER Bead Technology) and Cellular prion protein (PrP(C)) in normal cerebro-spinal-fluid (CSF) of urban children with high vs. low air pollution exposures. PrP(C) and macrophage inhibitory factor (MIF) were also measured in serum. Samples from 139 children ages 11.91 ± 4.2 years were measured. Highly exposed children exhibited significant increases in CSF MIF (p = 0.002), IL6 (p = 0.006), IL1ra (p = 0.014), IL-2 (p = 0.04), and PrP(C) (p = 0.039) vs. controls. MIF serum concentrations were higher in exposed children (p = 0.009). Our results suggest CSF as a MIF, IL6, IL1Ra, IL-2, and PrP(C) compartment that can possibly differentiate air pollution exposures in children. MIF, a key neuro-immune mediator, is a potential biomarker bridge to identify children with CNS inflammation. Fine tuning of immune-to-brain communication is crucial to neural networks appropriate functioning, thus the short and long term effects of systemic inflammation and dysregulated neural immune responses are of deep concern for millions of exposed children. Defining the linkage and the health consequences of the brain / immune system interactions in the developing brain chronically exposed to air pollutants ought to be of pressing importance for public

  19. Effect of intraoperative intravenous lidocaine on pain and plasma interleukin-6 in patients undergoing hysterectomy

    Directory of Open Access Journals (Sweden)

    Caio Marcio Barros de Oliveira

    2015-04-01

    Full Text Available BACKGROUND AND OBJECTIVES: Interleukin-6 is a predictor of trauma severity. The purpose of this study was to evaluate the effect of intravenous lidocaine on pain severity and plasma interleukin-6 after hysterectomy. METHOD: A prospective, randomized, comparative, double-blind study with 40 patients, aged 18-60 years. G1 received lidocaine (2 mg kg-1 h-1 or G2 received 0.9% saline solution during the operation. Anesthesia was induced with O2/isoflurane. Pain severity (T0: awake and 6, 12, 18 and 24 h, first analgesic request, and dose of morphine in 24 h were evaluated. Interleukin-6 was measured before starting surgery (T0, 5 h after the start (T5, and 24 h after the end of surgery (T24. RESULTS: There was no difference in pain severity between groups. There was a decrease in pain severity between T0 and other measurement times in G1. Time to first supplementation was greater in G2 (76.0 ± 104.4 min than in G1 (26.7 ± 23.3 min. There was no difference in supplemental dose of morphine between G1 (23.5 ± 12.6 mg and G2 (18.7 ± 11.3 mg. There were increased concentrations of IL-6 in both groups from T0 to T5 and T24. There was no difference in IL-6 dosage between groups. Lidocaine concentration was 856.5 ± 364.1 ng mL-1 in T5 and 30.1 ± 14.2 ng mL-1 in T24. CONCLUSION: Intravenous lidocaine (2 mg kg-1 h-1 did not reduce pain severity and plasma levels of IL-6 in patients undergoing abdominal hysterectomy.

  20. Diagnostic performance of interleukin-6 and interleukin-8 for bacterial meningitis: a meta-analysis

    Science.gov (United States)

    Yao, Rong; Cao, Yu; Chen, Yao; Zeng, Zhi

    2015-01-01

    This study aimed to summarize the overall diagnostic performance of interleukin-6 and interleukin-8 in cerebrospinal fluid for bacterial meningitis through meta-analysis due to inconclusive results reported. Literature search was performed in PubMed and Embase to identify eligible studies. Data were retrieved and sensitivity, specificity, positive likelihood ratio/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR) were pooled. Summary receiver operating characteristic curve and the area under the curve (AUC) were calculated to evaluate their overall test performances. Thirteen studies were included for present meta-analysis. The summary estimates for interleukin-6 in diagnosing bacterial meningitis were: sensitivity, 0.91 (95% CI 0.81-0.96); specificity, 0.93 (95% CI 0.84-0.97); PLR, 12.38 (95% CI 5.42-28.29); NLR, 0.10 (95% CI 0.04-0.21); DOR, 129.76 (95% CI 41.48-405.88); and AUC 0.97 (95% CI 0.95-0.98). The corresponding summary performance estimates for interleukin-8 were as follows: sensitivity, 0.95 (95% CI 0.71-0.99); specificity, 0.89 (95% CI 0.77-0.95); PLR, 8.50 (95% CI, 3.83-18.86); NLR, 0.06 (95% CI 0.01-0.40); DOR, 154.25 (95% CI 14.56-1634.33); and AUC 0.95 (95% CI 0.93-0.97). Measurements of interleukin-6 and interleukin-8 play a valuable role in diagnosing bacterial meningitis. Nevertheless, their results should be interpreted in parallel with the results of routine tests and clinical symptoms. PMID:26221243

  1. Interleukin-6 is not essential for bone turnover in hypothyroid mice.

    OpenAIRE

    Maria Gorska; Jerzy Walecki; Zofia Bondyra; Wlodzimierz Musial; Piotr Mysliwiec; Karol Kaminski; Agnieszkar Nikolajuk; Boguslaw Sawicki; Maria Winnicka; Robert Zbucki; Janusz Mysliwiec

    2008-01-01

    Interleukin-6 (IL-6) has been shown to be involved in the pathogenesis of several bone diseases characterized by an imbalance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b) and osteocalcin in IL-6-deficient mice to assess the role of IL-6 in bone metabolism in hypothyroidism in mice. C57BL/6J (wild-type; WT) and C57BL/6J(IL6-/-Kopf) (IL-6 knock-out; IL6KO) mic...

  2. The Good, the Bad, and the Ugly of interleukin-6 signaling

    Science.gov (United States)

    Fuster, José J; Walsh, Kenneth

    2014-01-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine with complex roles in inflammation and metabolic disease. While typically regarded as a pro-inflammatory cytokine, multiple studies in the last 20 years have generated conflicting data on the role of IL-6 in inflammation and metabolism. In a recent study in Nature Immunology, Brüning and collaborators demonstrate that IL-6 signaling in myeloid cells attenuates obesity-induced inflammation and insulin resistance by promoting macrophage alternative activation (Mauer et al, 2014). This study unveils a new and surprising anti-inflammatory action of IL-6 and further highlights the complex actions of this cytokine. PMID:24850773

  3. Promotion of Endoplasmic Reticulum-Associated Degradation of Procathepsin D by Human Herpesvirus 8-Encoded Viral Interleukin-6

    OpenAIRE

    Chen, Daming; Nicholas, John

    2015-01-01

    The interleukin-6 homologue (viral interleukin-6 [vIL-6]) of human herpesvirus 8 is implicated in viral pathogenesis due to its proproliferative, inflammatory, and angiogenic properties, effected through gp130 receptor signaling. In primary effusion lymphoma (PEL) cells, vIL-6 is expressed latently and is essential for normal cell growth and viability. This is mediated partly via suppression of proapoptotic cathepsin D (CatD) via cocomplexing of the endoplasmic reticulum (ER)-localized CatD p...

  4. Suppression of interleukin-6-induced C-reactive protein expression by FXR agonists

    International Nuclear Information System (INIS)

    Zhang Songwen; Liu Qiangyuan; Wang Juan; Harnish, Douglas C.

    2009-01-01

    C-reactive protein (CRP), a human acute-phase protein, is a risk factor for future cardiovascular events and exerts direct pro-inflammatory and pro-atherogenic properties. The farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily, plays an essential role in the regulation of enterohepatic circulation and lipid homeostasis. In this study, we report that two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6-induced CRP expression in human Hep3B hepatoma cells. Knockdown of FXR by short interfering RNA attenuated the inhibitory effect of the FXR agonists and also increased the ability of interleukin-6 to induce CRP production. Furthermore, treatment of wild type C57BL/6 mice with the FXR agonist, WAY-362450, attenuated lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver, whereas no effect was observed in FXR knockout mice. These data provide new evidence for direct anti-inflammatory properties of FXR.

  5. Modern and Convensional Wound Dressing to Interleukin 1 and Interleukin 6 in Diabetic wound

    Directory of Open Access Journals (Sweden)

    Werna Nontji

    2015-04-01

    Full Text Available Introduction:Holistic wound care is one of the ways to prevent gangrene and amputation, modern wound dressing is more effective than convensional with increasing transforming growth factor and cytokine, especially interleukin. This study aims to identify the effectiveness of Modern and Convensional Wound Dressing to Interleukin 1 (IL-1 and Interleukin 6 (IL-6 in Diabetic wound. Method:A Quasi eksperimental pre-post with control group design was used. The intervention given was modern wound dressing and Control group by convensional wound dressing, This study was conducted in Makassar with 32 samples (16 in intervention group and 16 in control group. Result: The result of Pooled T- test showed that p = 0.00 (p < 0.05, it means that there was signifi cant correlation between modern wound dressing to IL-6 and IL-1 than Convensional wound dressing. Discussion: Process of wound healing was produced growth factor and cytokine (IL-1 and IL-6, it will stimulated by wound dressing, modern wound dressing (Calcium alginat can absorb wound drainage, non oklusive, non adhesif, and autolytic debridement. Keywords: Modern wound dressing, Interleukin 1 (IL-1, Interleukin 6 (IL-6

  6. High interleukin-6 mRNA expression is a predictor of relapse in colon cancer

    DEFF Research Database (Denmark)

    Olsen, Jesper; Kirkeby, Lene T; Olsen, Jørgen

    2015-01-01

    AIM: To investigate the expression of interleukin-6 (IL6) in colon cancer tissue, and to examine if the risk of relapse is influenced by IL6 expression. MATERIALS AND METHODS: Fresh-frozen biopsies from tumor and normal adjacent tissues were taken from patients with colon cancer during surgery an...... for clinicopathological characteristics (Hazard Ratio=2.16, 95% CI=1.07-4.40; pcolon cancer tissue at the transcriptional level and is significantly associated with increased risk of relapse.......AIM: To investigate the expression of interleukin-6 (IL6) in colon cancer tissue, and to examine if the risk of relapse is influenced by IL6 expression. MATERIALS AND METHODS: Fresh-frozen biopsies from tumor and normal adjacent tissues were taken from patients with colon cancer during surgery...... to normal adjacent tissue (pcancer stage. We found a significant association between high IL6 expression and risk of relapse (Hazard Ratio=2.23, 95% CI=1.10-4.53; p

  7. Angiotensin II induces interleukin-6 expression in astrocytes: Role of reactive oxygen species and NF-κB.

    Science.gov (United States)

    Gowrisankar, Yugandhar V; Clark, Michelle A

    2016-12-05

    Previously, we showed that the bio-peptide angiotensin (Ang) II induces interleukin-6 (IL-6) in cultured astrocytes; however, the mechanism(s) involved in this effect were unknown. In the current study, we determined in brainstem and cerebellum astrocytes from the spontaneously hypertensive rat (SHR), the effect of Ang II to induce IL-6 as well as reactive oxygen species (ROS) generation. Results from this study showed that Ang II significantly induced the differential expression of IL-6 mRNA and protein levels in astrocytes from both regions of Wistar and SHRs. There were differences in the ability of Ang II to induce IL-6 mRNA and protein levels, but these differences were not apparent at all time points examined. Ang II also induced ROS generation, but there were no significant differences between ROS generation in SHR samples as compared to the Wistar samples. Ang II-induced IL-6 levels were mediated via the AT 1 /Nuclear Factor Kappa beta/ROS pathway. Overall, our findings suggest that there may be dysregulation in IL-6 production from astrocytes, contributing to differences observed in SHRs versus its normotensive control. Elucidating the mechanisms involved in Ang II pro-inflammatory effects in the central nervous system may lead to the development of novel therapeutic strategies that can be harnessed not just to treat hypertension, but other Ang II-mediated diseases as well. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Expression profiling and Ingenuity biological function analyses of interleukin-6- versus nerve growth factor-stimulated PC12 cells

    Directory of Open Access Journals (Sweden)

    Dimitriades-Schmutz Beatrice

    2009-02-01

    Full Text Available Abstract Background The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6 and the neurotrophin (NT Nerve Growth Factor (NGF for neuronal differentiation. Results The designer cytokine Hyper-IL-6 in which IL-6 is covalently linked to its soluble receptor s-IL-6R as well as NGF were used to stimulate PC12 cells for 24 hours. Changes in gene expression levels were monitored using Affymetrix GeneChip technology. We found different expression for 130 genes in IL-6- and 102 genes in NGF-treated PC12 cells as compared to unstimulated controls. The gene set shared by both stimuli comprises only 16 genes. A key step is upregulation of growth factors and functionally related external molecules known to play important roles in neuronal differentiation. In particular, IL-6 enhances gene expression of regenerating islet-derived 3 alpha (REG3A; 1084-fold, regenerating islet-derived 3 beta (REG3B/PAPI; 672-fold, growth differentiation factor 15 (GDF15; 80-fold, platelet-derived growth factor alpha (PDGFA; 69-fold, growth hormone releasing hormone (GHRH; 30-fold, adenylate cyclase activating polypeptide (PACAP; 20-fold and hepatocyte growth factor (HGF; 5-fold. NGF recruits GDF15 (131-fold, transforming growth factor beta 1 (TGFB1; 101-fold and brain-derived neurotrophic factor (BDNF; 89-fold. Both stimuli activate growth-associated protein 43 (GAP-43 indicating that PC12 cells undergo substantial neuronal differentiation. Moreover, IL-6 activates the transcription factors retinoic acid receptor alpha (RARA; 20-fold and early growth response 1 (Egr1/Zif268; 3-fold known to play key roles in neuronal differentiation. Ingenuity biological function analysis revealed that completely different repertoires of molecules are recruited to exert the same biological functions in neuronal differentiation. Major sub-categories include cellular growth and differentiation, cell migration, chemotaxis, cell

  9. Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis.

    Science.gov (United States)

    Gillies, Nicola; Pendharkar, Sayali A; Asrani, Varsha M; Mathew, Juby; Windsor, John A; Petrov, Maxim S

    2016-01-01

    Diabetes is a pervasive disease, with a mounting prevalence and burden on health care systems. Under this collective term of diabetes falls diabetes after diseases of the exocrine pancreas, a condition which was previously under-recognised and often mislabeled as type 2 diabetes mellitus and is now increasingly acknowledged as a stand-alone entity. However, there is a paucity of clinical studies investigating the underlying pathophysiology of diabetes after acute pancreatitis, the most frequent disease of the pancreas. This study aimed to investigate the role of adipocytokines in glucose metabolism after acute pancreatitis. This was a cross-sectional follow-up study of a patient cohort diagnosed with acute pancreatitis. Fasting venous blood samples were collected to analyse markers of glucose metabolism (fasting blood glucose, haemoglobin A1c, homeostasis model assessment (HOMA-IR) as a measure of insulin resistance) and adypocytokines (adiponectin, interleukin-6, leptin, monocyte chemoattractant protein-1, retinol binding protein-4, resistin, and tumor necrosis factor-α). Participants were categorized into two groups: normoglycemia after acute pancreatitis and chronic hyperglycemia after acute pancreatitis (CHAP). Binary logistic regression and linear regression analyses were used to investigate the association between each of the adipocytokines and markers of glucose metabolism. Potential confounders were adjusted for in multivariate analyses. A total of 83 patients with acute pancreatitis were included, of whom 19 developed CHAP. Interleukin-6 was significantly associated with CHAP in both unadjusted and adjusted models (p = 0.030 and p = 0.018, respectively). Further, it was also significantly associated with HOMA-IR in both unadjusted and adjusted models (p = 0.029 and p = 0.037, respectively). Other adipocytokines were not significantly associated with markers of glucose metabolism. Interleukin-6 appears to be implicated in the development of chronic

  10. Identification and predictive value of interleukin-6+ interleukin-10+ and interleukin-6-interleukin-10+ cytokine patterns in st-elevation acute myocardial infarction

    KAUST Repository

    Ammirati, Enrico

    2012-08-29

    RATIONALE: At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6) levels or very low-IL-6 levels. OBJECTIVE: We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response. METHODS AND RESULTS: We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6 STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6 STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6 STEMI and IL-6 STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6 STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and monokine induced by interferon-γ. IL-10 was increased both in IL-6 STEMI and IL-6 STEMI patients compared with controls. IL-6IL-10 STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6IL-10 STEMI patients. We combined IL-10 and monokine induced by interferon-γ (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death. CONCLUSIONS: We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes

  11. VEGF targeting in mesotheliomas using an interleukin-6 signal inhibitor based on adenovirus gene delivery.

    Science.gov (United States)

    Adachi, Yasuo; Yoshio-Hoshino, Naoko; Aoki, Chieko; Nishimoto, Norihiro

    2010-06-01

    Malignant mesotheliomas reportedly secrete interleukin-6 (IL-6) which augments production of vascular endothelial growth factor (VEGF) from mesothelioma cells. We previously reported the development of a new receptor inhibitor of IL-6 (NRI) by genetically engineering tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody. Since NRI is encoded on a single gene, it is easily applicable to a gene delivery system using virus vehicles. In this study, we report VEGF targeting through NRI expression based on adenovirus-mediated gene delivery in mesothelioma cells. We constructed an NRI expression vector in the context of a tropism-modified adenovirus vector that had enhanced infectivity in mesothelioma cells. This virus effectively induced NRI secretion from mesothelioma cells. This virus infection also reduced the VEGF production in mesothelioma cells. These results indicate that NRI shows potential as an agent in the treatment of mesotheliomas.

  12. S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma

    DEFF Research Database (Denmark)

    de Nully Brown, P; Jensen, P O; Diamant, M

    1998-01-01

    .0 microg/kg (n = 6) by subcutaneous injection once daily for 5 days and chemotherapy was administered on the last day of rhIL-6 injection. The effect of rhIL-6 treatment on labeling index (LI) was heterogeneous, but no statistically significant change was noted for this particular group as a whole. In two......, our study demonstrated that rhIL-6 can be administered safely to patients with refractory MM, but the cell cycle recruitment approach was not sufficiently effective to be of clinical value.......The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S...

  13. Correlation between CT grading and blood interleukin-6 in severe acute pancreatitis

    International Nuclear Information System (INIS)

    Yokohari, Kenji; Hirasawa, Hiroyuki; Oda, Shigeto; Shiga, Hidetoshi; Nakanishi, Kazuya; Nakamura, Masataka

    2003-01-01

    Computed tomography (CT) and an evaluating of the degree of severity in patients with severe acute pancreatitis (SAP) are required to decide the therapeutic strategy. We measured blood interleukin-6 (IL-6) in critically ill patients at our intensive care unit (ICU) in a daily clinical setting. To determine the significance of grading CT findings in SAP, we studied the correlation between CT grading and blood IL-6 in SAP patients on ICU admission. Among 31 SAP cases, 66 were CT grade III, 22 CT grade IV, and 3 cases CT grade V. Patients with a higher CT grade tended to have higher blood IL-6. Data also showed that mean blood IL-6 among SAP patients in stage 2 was significantly higher than that among those in stage 3 (p<0.05). From these results, we concluded that CT grading and IL-6 blood level have a different significance in the management of SAP patients. (author)

  14. Metabolic effects of interleukin-6 in human splanchnic and adipose tissue

    DEFF Research Database (Denmark)

    Lyngsø, Dorthe; Simonsen, Lene; Bülow, Jens

    2002-01-01

    Interleukin-6 (IL-6) was infused intravenously for 2.5 h in seven healthy human volunteers at a dose giving rise to a circulating IL-6 concentration of approximately 35 ng l(-1). The metabolic effects of this infusion were studied in subcutaneous adipose tissue on the anterior abdominal wall...... and in the splanchnic tissues by the Fick principle after catheterizations of an artery, a subcutaneous vein draining adipose tissue, and a hepatic vein, and measurements of regional adipose tissue and splanchnic blood flows. In control studies without IL-6 infusion subcutaneous adipose tissue metabolism was studied...... infusion. It is concluded that IL-6 elicits lipolytic effects in human adipose tissue in vivo, and that IL-6 also has effects on the splanchnic lipid and carbohydrate metabolism....

  15. Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships.

    LENUS (Irish Health Repository)

    O'Donovan, Aoife

    2012-02-01

    Anxiety confers increased risk for inflammatory diseases, and elevated inflammatory activity in anxious individuals may contribute to this increased risk. One complication, however, is that anxiety could be associated with inflammatory activity either through a specific anxiety pathway or through a more general negative emotionality pathway. To investigate, we measured levels of the stress hormone cortisol, the pro-inflammatory cytokine interleukin-6 (IL-6), and the systemic inflammatory marker C-reactive protein (CRP), as well as depression and neuroticism, in clinically anxious and non-anxious adults. Compared with non-anxious participants, clinically anxious participants exhibited significantly lower levels of morning cortisol and significantly higher levels of IL-6, independent of age, sex, and depressive symptoms. These group differences were robust when controlling for neuroticism. Conversely, the groups had equivalent levels of CRP in all analyses. Results are indicative of anxiety-specific effects on inflammatory activity, and highlight a pathway by which anxiety may increase risk for inflammatory diseases.

  16. Sex Differences in the Association between Level of Childhood Interleukin-6 and Insulin Resistance in Adolescence

    DEFF Research Database (Denmark)

    Bugge, Anna; El-Naaman, Bianca; G McMurray, Robert

    2012-01-01

    The purpose of this study was to determine whether levels of interleukin-6 (IL-6) in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO(2peak)) moderate this relationship. Methods. 292 nine-year-old children (n = 292) were......-IR at age 13 yrs: r = 0.223, P = 0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58-8.57) being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence...

  17. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T; Carrasco, J

    1999-01-01

    and reactive astrocytes surrounding the lesion site. In addition, expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and metallothionein-I+II (MT-I+II) were increased in these cells, while the brain-specific MT-III was only moderately upregulated. In IL-6-/- mice, however, the response...... of brain macrophages and reactive astrocytes was markedly depressed and the number of NSE positive neurons was reduced. Brain damage-induced GM-CSF and MT-I+II expression were also markedly depressed compared to IL-6+/+ mice. In contrast, MT-III immunoreactivity was markedly increased in brain macrophages......Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory...

  18. Role of Interleukin-6 in the Radiation Response of Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Miao-Fen, E-mail: miaofen@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); College of Medicine, Chang Gung University, Taiwan (China); Hsieh, Ching-Chuan [College of Medicine, Chang Gung University, Taiwan (China); Department of General Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); Chen, Wen-Cheng [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); College of Medicine, Chang Gung University, Taiwan (China); Lai, Chia-Hsuan [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China)

    2012-12-01

    Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated in the presence of IL-6-neutralizing antibody for 24 hours or stably transfected with IL-6-silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6-silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.

  19. Serum concentrations of interleukin-1 alpha, interleukin-6 and tumor necrosis factor-alpha in neonatal sepsis and meningitis

    International Nuclear Information System (INIS)

    Fida, Nadia M.; Fadelallah, Mohamed F.; Al-Mughales, Jamil A.

    2006-01-01

    To investigate whether serum levels of interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) are useful in the diagnosis of neonatal sepsis and meningitis and differentiate them. Blood samples were collected from 35 full term neonates with suspected infection who admitted to the Neonatology Unit, Pediatric Department, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia during January 2002 - June 2003. On the basis of laboratory and bacteriological results, newborns were classified into: sepsis (n=28), meningitis (n=7), and healthy controls (n=16). Sepsis groups were further subdivided according to culture results into: group 1 = proven sepsis (n=6), group 2 = clinical sepsis (n=14), and group 3 = possible-infected (n=8). Serum levels of IL-1alpha, IL-6, TNF-alpha were measured using Enzyme-Linked Immunosorbent Assay while CRP by nephelometer: In sepsis and meningitis patients, serum levels of CRP (p<0.01, p<0.05,) and IL-1alpha (p<0.001, p<0.05) were elevated than controls. C-reactive protein levels elevated in proven sepsis (p<0.001) and IL-1alpha elevated in all subgroups of sepsis (groups 1, 2, 3) compared with (p<0.05, p<0.001, p<0.01) controls. Interleukin-6, TNF-alpha showed no significant differences between studied groups. In sepsis and meningitis, IL-1alpha had a highest sensitivity (89%, 86%), and negative predictive values (89% and 93%). Interleukin-1alpha and CRP increased in neonatal sepsis and meningitis, but cannot differentiate between them. Interleukin-1alpha had a highest sensitivity in prediction of neonatal infection and its assessment may improve accuracy of diagnosis. (author)

  20. Enhancing recombinant interleukin-6 production yield by fermentation optimization, two-step denaturing, and one-step purification.

    Science.gov (United States)

    Ahmed, Nadeem; Abbas, Rabbia; Khan, Mohsin Ahmad; Bashir, Hamid; Tahir, Saad; Zafar, Ahmad Usman

    2017-08-22

    Interleukin-6 a pleiotropic cytokine involved in a wide range of biological activities. So the large-scale production of biologically active recombinant human interleukin-6 is important for its structural and functional studies. Here, we report an optimized method for shake flask fermentation and a simplified high-yield purification procedure for the recombinant interleukin-6. This high-yield expression method not only involves the optimization of the fermentation condition but also the single step purification method as well as a two-step denaturing and one-step refolding process. This approach replaces the more conventional procedure of protein solubilization and refolding. Through applying these strategies, the final cell density and overall product yield of the recombinant human interleukin-6 were obtained as 20.4 g as cell biomass and 150 mg as purified active protein from the I-L of the culture. The purified protein was characterized by HPLC and SDS-PAGE. The results of the current work demonstrate that the described method may be used to develop the process for industrial-scale production of the biologically active recombinant interleukin-6 protein. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  1. Interleukin-6 levels in female rats with protamine sulfate-induced chronic cystitis treated with hyaluronic acid.

    Science.gov (United States)

    Lv, Yi-Song; Yao, You-Sheng; Lin, Ming-En; Rong, Lu; Deng, Bi-Hua; Huang, Jian; Hao, Wei-Ping

    2013-10-01

    To measure interleukin-6 levels in a protamine sulfate-induced chronic cystitis rat model treated with hyaluronic acid, and to study the correlation among interleukin-6, bladder inflammatory degree and voiding frequency. A chronic cystitis model was created in female rats by using long-term intermittent intravesical protamine sulfate (0.5 mL, 30 mg/mL). Then, hyaluronic acid (0.5 mL, 0.8 mg/mL) was also instilled intravesically in the rats. Interleukin-6 levels were analyzed with immunohistochemistry, real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was carried out to examine bladder inflammatory degree based on a four-point scoring system (from 0 - none to 3 - severe). Voiding patterns were investigated by cystometrography. According to cystometrography, protamine sulfate-induced rats had significantly shorter intercontraction intervals and less bladder capacity (P hyaluronic acid, both intercontraction intervals and bladder capacity increased significantly (P hyaluronic acid decreases interleukin-6 levels, as well as the severity of bladder inflammation and voiding frequency in a rat model of chronic cystitis. Interleukin-6 levels closely correlate with the inflammatory degree and voiding frequency. Thus, they can be regarded as an assessment measure of therapeutic impact. © 2013 The Japanese Urological Association.

  2. Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis.

    Science.gov (United States)

    Tournadre, Anne; Pereira, Bruno; Dutheil, Fréderic; Giraud, Charlotte; Courteix, Daniel; Sapin, Vincent; Frayssac, Thomas; Mathieu, Sylvain; Malochet-Guinamand, Sandrine; Soubrier, Martin

    2017-08-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality associated with cardiometabolic disorders including dyslipidaemia, insulin resistance, and cachectic obesity. Tumour necrosis factor inhibitors and interleukin 6 receptor blocker licensed for the treatment of RA decrease inflammation and could thus improve cardiovascular risk, but their effects on body composition and metabolic profile need to be clarified. We investigated the effects of tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, on body composition and metabolic profile in patients treated for RA. Twenty-one active RA patients treated with TCZ were included in a 1 year open follow-up study. Waist circumference, body mass index, blood pressure, lipid profile, fasting glucose, insulin, serum levels of adipokines and pancreatic/gastrointestinal hormones, and body composition (dual-energy X-ray absorptiometry) were measured at baseline and 6 and 12 months of treatment. At baseline, RA patients were compared with 21 non-RA controls matched for age, sex, body mass index, and metabolic syndrome. Compared with controls, body composition was altered in RA with a decrease in total and appendicular lean mass, whereas fat composition was not modified. Among RA patients, 28.6% had a skeletal muscle mass index below the cut-off point for sarcopaenia (4.8% of controls). After 1 year of treatment with TCZ, there was a significant weight gain without changes for fat mass. In contrast, an increase in lean mass was observed with a significant gain in appendicular lean mass and skeletal muscle mass index between 6 and 12 months. Distribution of the fat was modified with a decrease in trunk/peripheral fat ratio and an increase in subcutaneous adipose tissue. No changes for waist circumference, blood pressure, fasting glucose, and atherogenic index were observed. Despite weight gain during treatment with TCZ, no increase in fat but a modification in fat

  3. Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery.

    Science.gov (United States)

    Hahn, Ulrich

    2017-12-06

    Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2'-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers-in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  4. Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells.

    Science.gov (United States)

    Ogawa, Hiroyuki; Koyanagi-Aoi, Michiyo; Otani, Kyoko; Zen, Yoh; Maniwa, Yoshimasa; Aoi, Takashi

    2017-09-26

    In the present study, we successfully generated lung cancer stem cell (CSC)-like cells by introducing a small set of transcription factors into a lung cancer cell line. In addition to properties that are conventionally referred to as CSC properties, the lung induced CSCs exhibited the ability to form lung cancer-like tissues in vitro with vascular cells and mesenchymal stem cells, which showed structures and immunohistological patterns that were similar to human lung cancer tissues. We named them "lung cancer organoids". We found that interleukin-6 (IL-6), which was expressed in the lung induced CSCs, facilitates the formation of lung cancer organoids via the conversion of mesenchymal stem cells into alpha-smooth muscle actin (αSMA)-positive cells. Interestingly, the combination of anti-IL-6 antibody and cisplatin could destroy the lung cancer organoids, while cisplatin alone could not. Furthermore, IL-6 mRNA-positive cancer cells were found in clinical lung cancer samples. These results suggest that IL-6 could be a novel therapeutic target in lung cancer.

  5. EFFECT OF TWO TAPERING METHODS ON INTERLEUKIN-6, CORTISOL AND PERFORMANCE IN ELITE MALE WRESTLER

    Directory of Open Access Journals (Sweden)

    A.B. Mehranpour

    2015-08-01

    Full Text Available Purpose : This study examined that effect of two types of tapering on interleukin-6(IL-6, cortisol and performance in elite male wrestler. Material : After 4 weeks of progressive training, wrestlers were randomly divided into three equal groups, 1-control group (N=10 continued performing progressive training for one week, 2-taper group 1 (N=10 continued with a 50% reduction in training volume for one week, 3-taper group 2 (N=10 continued with a 75% reduction in volume of training for one week .plasma blood IL-6 and cortisol levels were assayed from analysis obtained via standard ELISA. Also general strength of muscles was recorded as a performance test. All data were collected before and after progressive training and also after one week of tapering period. Results : There were significant reduction of IL-6 and cortisol levels in both tapering group comparing with control group (P≤0.05.There was significant reduction of IL-6 and cortisol levels among tapering 50% and tapering 75% after tapering period (P≤0.05. Also there was significant increase of general strength of muscles between tapering 75% and control group (P≤0.05. Conclusion : hence, one week tapering with 75% reduction in training volume after progressive training while the intensity kept high is effective strategy for reduction of IL-6, and cortisol levels and also increase performance. It seems that higher reduction of training volume when the intensity kept high is a good strategy for wrestler before main competition.

  6. Chemerin and interleukin-6 levels in obese individuals following periodontal treatment.

    Science.gov (United States)

    Balli, U; Ongoz Dede, F; Bozkurt Dogan, S; Gulsoy, Z; Sertoglu, E

    2016-10-01

    To investigate changes in the levels of gingival crevicular fluid (GCF) chemerin and interleukin-6 (IL-6) in both obese/non-obese individuals with periodontitis following non-surgical periodontal therapy. Individuals (n = 80) were split into four groupings according to periodontal/anthropometric parameters: (i) periodontal healthy without obesity; (ii) chronic periodontitis (CP) without obesity; (iii) periodontal healthy with obesity; and (iv) CP with obesity. Individuals with periodontitis were treated with non-surgical periodontal therapy. Both GCF sampling procedures and clinical periodontal measures were performed prior to treatment and 6 weeks thereafter. Enzyme-linked immunosorbent assay was utilized to measure both chemerin and IL-6 levels. Greater values for chemerin and IL-6 were observed in obese individuals compared to their non-obese controls and in individuals with CP compared to their periodontal healthy controls (P obese groups (P integral part in the pathologic mechanisms that relate adipokines to both periodontal disease and obesity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Salivary Interleukin-6 - A pioneering marker for correlating diabetes and chronic periodontitis: A comparative study

    Directory of Open Access Journals (Sweden)

    Anitha Balaji

    2017-01-01

    Full Text Available Background: Periodontitis is a chronic inflammatory disease which is multifactorial. Diabetes mellitus (DM is one of the major systemic factors to influence the severity of chronic periodontitis. Numerous inflammatory markers are produced in the course of the disease which is secreted in saliva too. This study evaluates the salivary concentrations of interleukin-6 (IL-6 in periodontitis patients with type 2 diabetes. Materials and Methods: Whole saliva samples were collected from eighty patients who were further divided into four groups; healthy (control group; n = 20, untreated periodontitis (UPD; n = 20, DM (DM; n = 20, and UPD + DM (n = 20 groups. Salivary IL-6 concentrations were determined by standard enzyme-linked immunosorbent assay. Results: Results show that the UPD patients with and without DM exhibited higher concentrations of salivary IL-6 than the control group and diabetes groups. Further, the salivary IL-6 was correlated with glycosylated hemoglobin A levels in patients with diabetes. Conclusion: Concentration of salivary IL-6 was elevated in patients with periodontitis with and without diabetes. Thus, salivary IL–6 levels can be considered as an important biomarker in the diagnosis of periodontitis and diabetes.

  8. miR-217 suppresses proliferation and promotes apoptosis in cardiac myxoma by targeting Interleukin-6.

    Science.gov (United States)

    Zhang, Jing; Wang, Cui; Xu, Huimin

    2017-08-26

    Cardiac myxoma (CM) is a prevalent primary cardiac tumor. miR-217 plays a vital role in tumorigenesis of various cancers, however, its role and underlying molecular mechanism in human CM remain poorly understood. Here, we reported that the expression of miR-217 was downregulated in CM tissues and inversely correlated with the expression of Interleukin-6 (IL-6) mRNA. Gain-of-function analysis indicated that overexpression of miR-217 inhibited the proliferation and promoted the apoptosis of the primary CM cells. Bioinformatics analysis showed that IL-6 was a direct target gene of miR-217, which is confirmed by the dual luciferase assays. Moreover, downregulation of IL-6 by small interference RNA (siRNA) mimicked the tumor-suppressive effects of miR-217 in CM. Furthermore, rescue experiments pointed out that restoration of IL-6 expression abrogated the anti-proliferative and pro-apoptotic effect induced by miR-217 overexpression in CM cells. Taken together, we validated that miR-217 could act as a tumor suppressor in CM by directly targeting 3'UTR of IL-6 gene, indicating that manipulation of miR-217 may be a potential therapeutic strategy for CM patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Role of interleukin-6 levels in cardiovascular autonomic dysfunction in type 2 diabetic patients

    International Nuclear Information System (INIS)

    Shinohara, Tetsuji; Takahashi, Naohiko; Kakuma, Tetsuya; Hara, Masahide; Yoshimatsu, Hironobu; Yufu, Kunio; Anan, Futoshi; Nakagawa, Mikiko; Saikawa, Tetsunori

    2008-01-01

    Increased serum interleukin-6 (IL-6) levels are associated with an increased risk of cardiovascular disease, and cardiovascular autonomic dysfunction is associated with high mortality in type 2 diabetic patients. However, the relationship between IL-6 levels and cardiovascular autonomic dysfunction has not been fully elucidated. The aim of this study was to determine whether serum IL-6 levels are associated with cardiovascular autonomic dysfunction in type 2 diabetic patients. Eighty type 2 diabetic patients who did not have organic heart disease were categorized into a high IL-6 group (>2.5 pg/ml, n= 0, age 59±12 years) or a non-high IL-6 group ( 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. The body mass index values (BMI), fasting insulin levels and homeostasis model assessment index values were higher in the high IL-6 group than in the non-high IL-6 group (p 123 I-MIBG myocardial uptake values were lower (p 123 I-MIBG was higher (p 123 I-MIBG during the delayed phase. The results indicate that elevated IL-6 levels are associated with depressed cardiovascular autonomic function and obesity in type 2 diabetic patients. (orig.)

  10. Interleukin-6 deficiency attenuates angiotensin II-induced cardiac pathogenesis with increased myocyte hypertrophy.

    Science.gov (United States)

    Chen, Fan; Chen, Dandan; Zhang, Yubin; Jin, Liang; Zhang, Han; Wan, Miyang; Pan, Tianshu; Wang, Xiaochuan; Su, Yuheng; Xu, Yitao; Ye, Junmei

    2017-12-16

    Interleukin-6 (IL-6) signaling is critical for cardiomyocyte hypertrophy, while the role of IL-6 in the pathogenesis of myocardium hypertrophy remains controversial. To determine the essential role of IL-6 signaling for the cardiac development during AngII-induced hypertension, and to elucidate the mechanisms, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were infused subcutaneously with either vehicle or AngII (1.5 μg/h/mouse) for 1 week. Immunohistological and serum studies revealed that the extents of cardiac fibrosis, inflammation and apoptosis were reduced in IL-6 KO heart during AngII-stimulation, while cardiac hypertrophy was obviously induced. To investigate the underlying mechanisms, by using myocardial tissue and neonatal cardiomyocytes, we observed that IL-6/STAT3 signaling was activated under the stimulation of AngII both in vivo and in vitro. Further investigation suggested that STAT3 activation enhances the inhibitory effect of EndoG on MEF2A and hampers cardiomyocyte hypertrophy. Our study is the first to show the important role of IL-6 in regulating cardiac pathogenesis via inflammation and apoptosis during AngII-induced hypertension. We also provide a novel link between IL-6/STAT3 and EndoG/MEF2A pathway that affects cardiac hypertrophy during AngII stimulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Charomers—Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ulrich Hahn

    2017-12-01

    Full Text Available Interleukin-6 (IL-6 is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT. Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2′-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers—in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

  12. Effects of lipopolysaccharide and interleukin-6 on cataleptic immobility and locomotor activity in mice.

    Science.gov (United States)

    Bazovkina, Daria V; Tibeikina, Marina A; Kulikov, Alexander V; Popova, Nina K

    2011-01-10

    Catalepsy (animal hypnosis, tonic immobility) is a type of passive defensive behavior. Its exaggerated form is a syndrome of some psychopathological disorders. Numerous neurotransmitters have impact on the regulation of catalepsy. In this paper we demonstrated the involvement of interleukin-6 (IL-6) in the mechanism of cataleptic immobility. Effects of exogenous IL-6 treatment (7.5 and 10μg/kg, i.p) or stimulation of endogenous IL-6 secretion with lipopolysaccharide (LPS) administration (50, 100 and 200μg/kg, i.p.) on catalepsy and locomotor activity were studied in adult C57BL/6 male mice. IL-6 induced catalepsy in 70% (7.5μg/kg) or 72.7% (10μg/kg) of animals with no effect on locomotor activity. LPS administration reduced distance travelled and number of rears in the open field at any dose used, however, only high doses (100 or 200μg/kg) of the toxin induced catalepsy in 50% of mice. This result indicates that IL-6 is involved in the regulation of catalepsy, this effect is specific and does not arise from inhibition of locomotor activity. The study provides a new evidence on participation of IL-6 in mechanisms of abnormal behavior. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Effect of Periodontal Therapy on Crevicular Fluid Interleukin-6 and Interleukin-8 Levels in Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Paschalina Goutoudi

    2012-01-01

    Full Text Available Purpose. The aim of this study was to analyse the levels of interleukin-6 (IL-6 and interleukin-8 (IL-8 in gingival crevicular fluid (GCF of patients with chronic periodontitis prior to and following surgical and/or nonsurgical periodontal therapy for a period of 32 weeks. Methods. GCF samples were obtained from 24 nondiseased and 72 diseased sites of 12 periodontal patients prior to as well as at 6, 16, and 32 weeks following non-surgical and surgical periodontal therapy. IL-6 and IL-8 levels were determined by enzyme-linked immunosorbent assay (ELISA. Results. Periodontal treatment improved all clinical parameters. Both treatment modalities resulted in similar IL-6 as well as IL-8 levels. Mean IL-6 and IL-8 concentrations were significantly higher in non-diseased compared to diseased sites and increased significantly following treatment in diseased sites. Mean total amounts of IL-6 and IL-8 (TAIL-6, TAIL-8 did not differ significantly between diseased and nondiseased sites, while following therapy TAIL-8 levels decreased significantly. Conclusions. The data suggest that periodontal therapy reduced the levels of IL-8 in GCF. However, a strong relationship between IL-6, IL-8 amounts in GCF and periodontal destruction and inflammation was not found.

  14. Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Shiga

    2016-01-01

    Full Text Available Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6 in colorectal cancer (CRC. Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS and disease-free survival (DFS rates according to IL-6 status were calculated for all patients and according to disease stage. Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients. Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.

  15. Interleukin 6 variable number of tandem repeats (VNTR) gene polymorphism in centenarians.

    Science.gov (United States)

    Capurso, C; Solfrizzi, V; D'Introno, A; Colacicco, A M; Capurso, S A; Semeraro, C; Capurso, A; Panza, F

    2007-11-01

    Recent population-based studies identified the magnitude of interleukin 6 (IL6) serum levels as a marker for functional disability, and a predictor of disability and mortality among the elderly. We investigated whether there was evidence in Southern Italy of an association between the IL6 gene variable number of tandem repeats (VNTR) polymorphism and extreme longevity, and tested for the possible interaction of apolipoprotein E (APOE) alleles with the IL6 VNTR alleles. Four alleles coding for variants of four different lengths have been identified: allele A [760 base pairs (bp)], allele B (680 bp), allele C (640 bp), and allele D (610 bp). IL6 VNTR and APOE allele and genotype frequencies were studied in a total of 61 centenarians and 94 middle-aged subjects from Southern Italy. The IL6 VNTR allele B was overrepresented in the younger control group compared with centenarians (odds ratio: 0.56, 95% confidence interval: 0.35-0.88, Bonferroni p-value VNTR alleles and APOE alleles on the odds ratios to reach extreme longevity were evaluated for the smallest number of subjects in centenarians and younger controls. Our findings suggested that the presence of the IL6 VNTR allele B could be detrimental for reaching extreme longevity.

  16. Negative Emotions Predict Elevated Interleukin-6 in the United States but not in Japan

    Science.gov (United States)

    Miyamoto, Yuri; Boylan, Jennifer Morozink; Coe, Christopher L.; Curhan, Katherine B.; Levine, Cynthia S.; Markus, Hazel Rose; Park, Jiyoung; Kitayama, Shinobu; Kawakami, Norito; Karasawa, Mayumi; Love, Gayle D.; Ryff, Carol D.

    2013-01-01

    Previous studies conducted in Western cultures have shown that negative emotions predict higher levels of pro-inflammatory biomarkers, specifically interleukin-6 (IL-6). This link between negative emotions and IL-6 may be specific to Western cultures where negative emotions are perceived to be problematic and thus may not extend to Eastern cultures where negative emotions are seen as acceptable and normal. Using samples of 1044 American and 382 Japanese middle-aged and older adults, we investigated whether the relationship between negative emotions and IL-6 varies by cultural context. Negative emotions predicted higher IL-6 among American adults, whereas no association was evident among Japanese adults. Furthermore, the interaction between culture and negative emotions remained even after controlling for demographic variables, psychological factors (positive emotions, neuroticism, extraversion), health behaviors (smoking status, alcohol consumption), and health status (chronic conditions, BMI). These findings highlight the role of cultural context in shaping how negative emotions affect inflammatory physiology and underscore the importance of cultural ideas and practices relevant to negative emotions for understanding of the interplay between psychology, physiology, and health. PMID:23911591

  17. AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6

    International Nuclear Information System (INIS)

    Miles, S.A.; Rezai, A.R.; Salazar-Gonzalez, J.F.; Meyden, M.V.; Stevens, R.H.; Mitsuyasu, R.T.; Martinez-Maza, O.; Logan, D.M.; Taga, Tetsuya; Hirano, Toshio; Kishimoto, Tadamitsu

    1990-01-01

    Cell lines derived from Kaposi sarcoma lesions of patients with AIDS (AIDS-KS cells) produce several cytokines, including an endothelial cell growth factor, interleukin 1β, and basic fibroblast growth factor. Since exposure to human immunodeficiency virus increases interleukin 6 (IL-6) production in monocytes and endothelial cells produce IL-6, the authors examined IL-6 expression and response in AIDS-KS cell lines and IL-6 expression in AIDS Kaposi sarcoma tissue. The AIDS-KS cell lines (N521J and EKS3) secreted large amounts of immunoreactive and biologically active IL-6. The authors found both IL-6 and IL-6 receptor (IL-6-R) RNA by slot blot hybridization analysis of AIDS-KS cells. The IL-6-R was functional, as [ 3 H]thymidine incorporation by AIDS-KS cells increased significantly after exposure to human recombinant IL-6 (hrIL-6) at >10 units/ml. When AIDS-KS cells (EKS3) were exposed to IL-6 antisense oligonucleotide, cellular proliferation decreased by nearly two-thirds, with a corresponding decrease in the production of IL-6. These results show that both IL-6 and IL-6-R are produced by AIDS-KS cells and that IL-6 is required for optimal AIDS-KS cell proliferation, and they suggest that IL-6 is an autocrine growth factor for AIDS-KS cells

  18. Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation

    Directory of Open Access Journals (Sweden)

    Sven Kruspe

    2014-01-01

    Full Text Available Photodynamic therapy (PDT uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on the development of photosensitizers to specifically target cancer cells. In the past few years, aptamers have been developed to directly deliver cargo molecules into target cells. We conjugated the photosensitizer chlorin e6 (ce6 with a human interleukin-6 receptor (IL-6R binding RNA aptamer, AIR-3A yielding AIR-3A-ce6 for application in high efficient PDT. AIR-3A-ce6 was rapidly and specifically internalized by IL-6R presenting (IL-6R+ cells. Upon light irradiation, targeted cells were selectively killed, while free ce6 did not show any toxic effect. Cells lacking the IL-6R were also not affected by AIR-3A-ce6. With this approach, we improved the target specificity of ce6-mediated PDT. In the future, other tumor-specific aptamers might be used to selectively localize photosensitizers into cells of interest and improve the efficacy and specificity of PDT in cancer and other diseases.

  19. Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites

    DEFF Research Database (Denmark)

    Hamid, Yasmin H; Urhammer, Søren A; Jensen, Dorit P

    2004-01-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the pathophysiology of various human diseases such as type 2 diabetes and obesity. IL-6 signals via a heterodimeric receptor complex consisting of a soluble IL-6 alpha-subunit (IL-6 receptor [IL6R]) and a signal transducing subunit (gp130......). The IL6R gene maps to an important candidate locus for type 2 diabetes on chromosome 1q21. An Asp358Ala polymorphism of the IL6R has been reported to associate with obesity in Pima Indians. We investigated the Asp358Ala polymorphism in relation to type 2 diabetes, obesity, and other pre-diabetic...... quantitative traits among Danish whites. By applying a recessive genetic model in a case-control study of 1,349 type 2 diabetic patients and 4,596 glucose-tolerant control subjects, we found a significant difference in genotype distribution (P = 0.008) and in allele frequency (Ala-allele 38.3% [95% CI 36...

  20. Interleukin-6 release is higher across arm than leg muscles during whole-body exercise

    DEFF Research Database (Denmark)

    Helge, Jørn W; Klein, Ditte K; Andersen, Thor Munch

    2011-01-01

    ± 7 and 47 ± 7 µmol min(-1) (kg lean limb mass)(-1)) were lower, glucose uptake similar (51 ± 12 and 41 ± 8 mmol min(-1) (kg lean limb mass)(-1)) and lactate release higher (82 ± 32 and -2 ± 12 µmol min(-1) (kg lean limb mass)(-1)) in arms than legs, respectively, during exercise (P ....05). No correlations were present between IL-6 release and exogenous substrate uptakes. Muscle glycogen was similar in arms and legs before exercise (388 ± 22 and 428 ± 25 mmol (kg dry weight)(-1)), but after exercise it was only significantly lower in the leg (219 ± 29 mmol (kg dry weight)(-1)). The novel finding......Exercising muscle releases interleukin-6 (IL-6), but the mechanisms controlling this process are poorly understood. This study was performed to test the hypothesis that the IL-6 release differs in arm and leg muscle during whole-body exercise, owing to differences in muscle metabolism. Sixteen...

  1. Socioeconomic and Psychosocial Predictors of Interleukin-6 in the MIDUS National Sample

    Science.gov (United States)

    Morozink, Jennifer A.; Friedman, Elliot M.; Coe, Christopher L.; Ryff, Carol D.

    2010-01-01

    Objective To investigate whether psychosocial factors (i.e., depression, anxiety, and well-being) moderate educational gradients in interleukin-6 (IL-6) levels using data from the Survey of Mid-life Development in the U.S. (MIDUS). The influences of educational attainment and psychosocial factors on IL-6 in middle aged and older adults were also examined. Design Telephone interviews and mail surveys were utilized to collect educational attainment and psychosocial information from participants (N = 1028). Respondents also participated in an overnight clinic visit, during which health information and a fasting blood sample was obtained. Main Outcome Measures Serum levels of IL-6. Results . Greater educational attainment predicted lower levels of IL-6 independent of age and gender, although this effect was attenuated after taking health behaviors, body mass index, waist-to-hip ratio, and chronic illnesses into account. Psychological well-being interacted with education to predict IL-6, such that for those with less education, higher well-being was associated with lower levels of IL-6. Conclusion The findings indicate a strong association between education and inflammation, which can be further moderated by psychosocial factors. The health benefits associated with psychological well-being were particularly evident for individuals with low educational attainment. PMID:20954777

  2. Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes

    DEFF Research Database (Denmark)

    Fosgerau, K; Galle, P; Hansen, T

    2010-01-01

    Interleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo. We tested the hypothesis that the prevalence of such aAb-IL6 is increased in type 2 diabetic patients and that aAb-IL6 plays a direct...... role in causing hyperglycemia. In humans, the prevalence of circulating high-affinity neutralizing aAb-IL6 was 2.5% in the type 2 diabetic patients and 1% in the controls (odds ratio 2.5, 95% confidence interval 1.2-4.9, P=0.01). To test for the role of aAb-IL6 in causing hyperglycemia, such aAb-IL6...... were induced in mice by a validated vaccination procedure. Mice with plasma levels of aAb-IL6 similar to the 2.5% type 2 diabetic patients developed obesity and impaired glucose tolerance (area under the curve (AUC) glucose, 2056+/-62 vs 1793+/-62, P=0.05) as compared with sham-vaccinated mice, when...

  3. Maternal serum interleukin-6 in the management of patients with preterm premature rupture of membranes.

    Science.gov (United States)

    Sayed Ahmed, Waleed Ali; Ahmed, Magdy Refaat; Mohamed, Mariam Lotfi; Hamdy, Mostafa Ahmed; Kamel, Zenab; Elnahas, Khaled Mohamed

    2016-10-01

    To evaluate the clinical usefulness of maternal serum interleukin-6 for the detection of subclinical chorioamnionitis and in the prediction of the latency period in patients with preterm premature rupture of membrane (PPROM). The study group included 60 patients at 24-34 weeks of gestation complaining of PPROM. Laboratory investigations included serial measurements of IL-6, TLC and CRP. Conservative management was carried out till 36 weeks unless delivery was indicated beforehand. The main outcome measures were the latency period and the occurrence of subclinical chorioamnionitis. The mean gestational age at presentation was 30.9 weeks and 35.2 weeks at delivery. The mean IL-6 level at presentation was 4.7 pg/ml. There was no correlation between IL-6 at presentation and the latency period. In addition, those diagnosed as having subclinical chorioamnionitis by placental histopathology had significantly higher levels of IL-6 at delivery. Taking IL-6 level cutoff point of 8.5 pg/ml, histological chorioamnionitis, RDS and NICU admission were significantly higher above that level while neonatal birth weight, Apgar scores at one and five minutes were significantly lower. Maternal serum IL-6 at the time of PPROM has no correlation to the latency period while IL-6 levels at the time of delivery have significant correlation to the subclinical chorioamnionitis and neonatal outcome measures.

  4. Association of Klotho and interleukin 6 gene polymorphisms with aging in Han Chinese population.

    Science.gov (United States)

    Zhang, W-G; Bai, X-J; Chen, D-P; Lv, Y; Sun, X-F; Cai, G-Y; Bai, X-Y; Chen, X-M

    2014-12-01

    Certain gene polymorphisms are associated with human aging. This study investigated polymorphisms of a metabolism-related gene, Klotho, and an inflammatory gene, IL6, for association with the aging process in a healthy Han Chinese population. A total of 482 healthy subjects were recruited and divided into aging and young groups according to chronological age and biological age. Snapshots were used to detect a Klotho gene tag SNP (rs571118) and the F-SNPs rs9536314 (F352V) and rs9527025 (C370S), and an interleukin 6 (IL-6) gene tag SNP (rs1524107) and the F-SNPs rs1800795 (-174G/C) and rs1800796 (-572G/C). Klotho F352V and IL-6-174G/C was G homozygous, C370S was T homozygous while IL-6-572G/C MAF less than 5%. There was a statistically significant difference in the Klotho rs571118 SNP between chronological age groups, but not biological age groups. However, other SNPs, including IL-6 gene SNPs, didn't correlate with age in the Han Chinese population. Human aging is a complex process that includes chronological and biological aging. Our current data showed that Klotho gene rs571118 SNP was associated with chronological aging, but not biological aging, in a Han Chinese population. Further study will investigate genetic build up for the difference between chronological and biological aging.

  5. Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer.

    Science.gov (United States)

    Han, Jun; Meng, Qingyang; Xi, Qiulei; Zhang, Yongxian; Zhuang, Qiulin; Han, Yusong; Jiang, Yi; Ding, Qiurong; Wu, Guohao

    2016-01-01

    Chronic inflammation is a well-known etiological factor for colorectal cancer (CRC) and cancer cells are known to preferentially metabolize glucose through aerobic glycolysis. However, the connection between chronic inflammation and aerobic glycolysis in the development of CRC is largely unexplored. The present study investigated whether interleukin-6 (IL-6), a pro-inflammatory cytokine, promotes the development of CRC by regulating the aerobic glycolysis and the underlying molecular mechanisms. In colitis-associated CRC mouse, anti-IL-6 receptor antibody treatment reduced the incidence of CRC and decreased the expression of key genes in aerobic glycolysis, whereas the plasma concentrations of glucose and lactate were not affected. Consistently, IL-6 treatment stimulated aerobic glycolysis, upregulated key genes in aerobic glycolysis and promoted cell proliferation and migration in SW480 and SW1116 CRC cells. 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was the most downregulated gene by anti-IL-6 receptor antibody in colorectal adenoma tissues. Further analysis in human samples revealed overexpression of PFKFB3 in colorectal adenoma and adenocarcinoma tissues, which was also associated with lymph node metastasis, intravascular cancer embolus and TNM stage. In addition, the effect of IL-6 on CRC cells can be abolished by knocking down PRKFB3 through siRNA transfection. Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of CRC.

  6. Immunoexpression of interleukin-6 in drug-induced gingival overgrowth patients

    Directory of Open Access Journals (Sweden)

    P R Ganesh

    2016-01-01

    Full Text Available Background: To analyze the role of proinflammatory cytokines in drug-induced gingival enlargement in Indian population. Aim: To evaluate for the presence of interleukin-6 (IL-6 in drug-induced gingival enlargement and to compare it with healthy control in the absence of enlargement. Materials and Methods: Thirty-five patients selected for the study and divided into control group (10 and study group (25 consisting of phenytoin (10; cyclosporin (10 and nifedipine (5 induced gingival enlargement. Gingival overgrowth index of Seymour was used to assess overgrowth and allot groups. Under LA, incisional biopsy done, tissue sample fixed in 10% formalin and immunohistochemically evaluated for the presence of IL-6 using LAB-SA method, Labeled- Streptavidin-Biotin Method (LAB-SA kit from Zymed- 2nd generation LAB-SA detection system, Zymed Laboratories, CA. The results of immunohistochemistry were statistically analyzed using Kruskaal–Wallis and Mann–Whitney test. Results: The data obtained from immunohistochemistry assessment shows that drug-induced gingival overgrowth (DIGO samples express more IL-6 than control group and cyclosporin expresses more IL-6 followed by phenytoin and nifedipine. Conclusion: Increased IL-6 expression was noticed in all three DIGO groups in comparison with control group. Among the study group, cyclosporin expressed maximum IL-6 expression followed by phenytoin and nifedipine.

  7. Hepcidin, interleukin-6 and hematological iron markers in males before and after heart surgery.

    Science.gov (United States)

    Hoppe, Michael; Lönnerdal, Bo; Hossain, Bakhtiar; Olsson, Sigvard; Nilsson, Folke; Lundberg, Per-Arne; Rödjer, Stig; Hulthén, Lena

    2009-01-01

    Anemia of inflammation in patients with acute or chronic acute-phase activation is a common clinical problem. Hepcidin is a peptide shown to be the principal regulator of the absorption and systemic distribution of iron. Main inducers of hepcidin are iron overload, hypoxia and inflammation, where the latter has been linked to hepcidin via increased interleukin-6 (IL-6). This article addresses the impact and time course of postoperative acute-phase reaction in humans following heart surgery on prohepcidin, hepcidin, hematological markers and IL-6 concentrations. Serum concentrations of prohepcidin, hepcidin, IL-6 and hematological iron parameters were studied in five male patients without infection before and after heart surgery. This study, which is the first to report the impact on serum hepcidin and serum prohepcidin concentrations in patients following surgery, clearly demonstrates the induction of hypoferremia due to the postoperative acute-phase reaction. Significant changes were seen for serum iron concentration, transferrin saturation, total iron binding capacity and hemoglobin concentration. A significant increase in ferritin concentration was seen 96-144 h postoperatively. Additionally, there were significant alterations in both serum hepcidin after 96-144 h and serum prohepcidin after 48 h compared with preoperative values. Serum prohepcidin decreased, whereas serum hepcidin increased. In conclusion, changes in serum prohepcidin were followed by an increase in serum hepcidin. This speaks in favor of a chain of action where proteolytic trimming of serum prohepcidin results in increased serum hepcidin. However, hypoferremia appeared prior to the changes in serum prohepcidin and serum hepcidin.

  8. Sex Differences in the Association between Level of Childhood Interleukin-6 and Insulin Resistance in Adolescence

    Directory of Open Access Journals (Sweden)

    Anna Bugge

    2012-01-01

    Full Text Available The purpose of this study was to determine whether levels of interleukin-6 (IL-6 in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO2peak moderate this relationship. Methods. 292 nine-year-old children (n=292 were followed for 4 years. Anthropometrics and VO2peak were measured. Fasting blood samples were analyzed for IL-6, insulin, and glucose. Homeostasis model assessment (HOMA-IR was used as a measure of insulin resistance. Results. For girls but not boys, levels of IL-6 at age 9 yrs correlated with HOMA-IR at age 13 yrs: r=0.223, P=0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58–8.57 being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence, but only for girls.

  9. Sex Differences in the Association between Level of Childhood Interleukin-6 and Insulin Resistance in Adolescence

    Science.gov (United States)

    Bugge, Anna; El-Naaman, Bianca; G. McMurray, Robert; Froberg, Karsten; Nielsen, Claus Henrik; Müller, Klaus; Andersen, Lars Bo

    2012-01-01

    The purpose of this study was to determine whether levels of interleukin-6 (IL-6) in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO2peak) moderate this relationship. Methods. 292 nine-year-old children (n = 292) were followed for 4 years. Anthropometrics and VO2peak were measured. Fasting blood samples were analyzed for IL-6, insulin, and glucose. Homeostasis model assessment (HOMA-IR) was used as a measure of insulin resistance. Results. For girls but not boys, levels of IL-6 at age 9 yrs correlated with HOMA-IR at age 13 yrs: r = 0.223, P = 0.008. Girls with IL-6 levels within the highest quartile at age 9 yrs had an odds ratio of 3.68 (CI = 1.58–8.57) being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence, but only for girls. PMID:22272193

  10. Prenatal expression of interleukin 1beta and interleukin 6 in the rat pituitary gland.

    Science.gov (United States)

    Moro, J A; Carretero, J; Alonso, M I; Martín, C; Gato, A; Mano, A de la

    2008-12-01

    It is known that interleukin 1beta (IL-1beta) and interleukin 6 (IL-6) are expressed post-natally in normal and tumoral cells in the anterior pituitary, and that they play a role in both the liberation of different hormones and in the growth, proliferation and tumor formation of the pituitary gland. However, their expression and role during embryonic and fetal development remain unknown. We have performed an immunocytochemistry study of prenatal expression and distribution of IL-1beta and IL-6 in isolated embryonic rat Rathke's pouch prior to birth, more specifically between 13.5 and 19.5 days p.c. Western-blot analysis carried out on 19.5-day p.c. embryos showed positive immunolabelling for IL-1beta and IL-6. These interleukins were initially expressed simultaneously in the rostral and ventral portions of Rathke's pouch in 15.5-day p.c. embryos, and this expression progressed caudodorsally in later developmental stages, extending to most of the hypophysis before birth. The number of cells expressing these interleukins increased throughout this period: 48.22% of anterior pituitary cells expressed IL-6 in 19.5-day embryos, whilst IL-1beta was positive in 39.8% of the cells. Moreover, we have demonstrated that some adenohypophyseal cells co-express both interleukins. Such findings represent the first step towards an understanding of the physiological role of these interleukins in anterior pituitary development.

  11. Simvastatin prevents the induction of interleukin-6 gene expression by titanium particles in human osteoblastic cells.

    Science.gov (United States)

    Vallés, Gema; Pérez, Concepción; Boré, Alba; Martín-Saavedra, Francisco; Saldaña, Laura; Vilaboa, Nuria

    2013-01-01

    One of the most important complications of total joint arthroplasty is failure associated with periprosthetic osteolysis, a process mainly initiated by the biological response to wear-derived products from the biomaterials in service. The inflammatory mediator interleukin-6 (IL-6) plays a key role in the establishment and progression of aseptic loosening. Metal particles specifically up-regulate IL-6 production in bone-forming cells and implant-bone interfacial tissues. The use of statins has been recently associated with a significantly reduced risk of revision in patients that undergo total hip arthroplasty. We hypothesized that simvastatin (Simv) could modulate the osteoblastic response to titanium particles (Ti) by attenuating the production of IL-6. Pre-treatment of human osteoblastic cells with Simv down-regulated Ti particle-induced IL-6 gene expression at mRNA and protein levels. The effect of Simv on Ti-induced IL-6 production in osteoblastic cells could not be explained by inhibition of the internalization of metal particles. The mechanism involved in this down-regulation is based in the inhibition of the HMG-CoA/GGPP/RhoA/ROCK pathway, independently of Simv effects in the cholesterol synthesis. The cytokine-lowering property of Simv has been observed in Saos-2 cells and human primary osteoblasts (hOBs) exposed to Ti particles, and was further enhanced when hOBs were co-cultured with macrophages. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  12. Serum Interleukin-6 Expression Level and Its Clinical Significance in Patients with Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Min Yang

    2013-01-01

    Full Text Available Objective. To analyze serum interleukin-6 (IL-6 expression level and its clinical significance in patients with dermatomyositis. Methods. Blood samples from 23 adult patients with dermatomyositis (DM, 22 with systemic lupus erythematosus (SLE, 22 with rheumatoid arthritis (RA, 16 with Sjögren's syndrome (SS, and 20 healthy controls were collected. The IL-6 concentration was detected by chemiluminescence immunoassay. Correlations between IL-6 expression levels and clinical features or laboratory findings in patients with DM were investigated. Results. IL-6 expression level of DM patients was significantly higher than that of normal controls, significantly lower than that of RA patients, and slightly lower than that of SLE or SS patients with no significant differences. The incidence of fever was significantly higher in the IL-6 elevated group. Serum ferritin (SF and C-reactive protein (CRP were positively correlated with IL-6. Conclusions. IL-6 plays a less important role in DM than in RA. IL-6 monoclonal antibodies may have poor effect in patients with DM.

  13. Plasma Levels of Tumor Necrosis Factor-Alpha and Interleukin-6 in Obsessive Compulsive Disorder

    Directory of Open Access Journals (Sweden)

    N. Konuk

    2007-01-01

    Full Text Available Aim. Recent research implicated place of an immune mechanism in the pathophysiology of obsessive-compulsive disorder (OCD. Despite increasing evidence involvement of cytokine release in OCD, results of the studies are inconsistent. The aim of this study was to evaluate the plasma levels of the cytokines; tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6 in OCD patients. Methods. Plasma concentrations of TNF-α and IL-6 were measured in 31 drug-free outpatients with OCD, and 31-year age and sex-matched healthy controls. TNF-α and IL-6 concentrations in blood were determined by enzyme-linked immunosorbent assay (ELISA. Results. Both TNF-α and IL-6 levels showed statistically significant increases in OCD patients compared to controls (P<.000, P<.001, resp.. In addition, the age of onset was negatively correlated with TNF-α level (r=−.402, P=.025 and duration of illness was weakly correlated with IL-6 levels (r:.357; P:.048 in patients group. Conclusion. OCD patients showed increases in TNF-α and IL-6 levels compared to the healthy controls. This study provides evidence for alterations in the proinflamatory cytokines which suggest the involvement of the immune system in the pathophysiology of OCD.

  14. Activation of the interleukin-6/Janus kinase/STAT3 pathway in pleomorphic adenoma of the parotid gland

    DEFF Research Database (Denmark)

    Andreasen, Simon; Therkildsen, Marianne Hamilton; Grauslund, Morten

    2015-01-01

    The interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway is of crucial importance in promoting tumorigenesis in several malignant tumors but may also be active in benign tumors, e.g., of pleomorphic adenoma (PA). In this study we characterize ...

  15. The effects of grain-induced subactue ruminal acidosis on interleukin-6 and acute phase response in dairy cows

    DEFF Research Database (Denmark)

    Li, Shucong; Danscher, Anne Mette; Andersen, Pia Haubro

    2014-01-01

    Subacute ruminal acidosis (SARA) resulting from excessive grain feeding to dairy cows is accompanied by an acute phase response. Interleukin 6 (IL-6) has been proposed as a mediator of this response. We tested if the acute phase response associated with grain-induced SARA is mediated by IL-6. Six...

  16. Astrocyte-targeted expression of interleukin-6 protects the central nervous system during neuroglial degeneration induced by 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Camats, Jordi; Hadberg, Hanne

    2003-01-01

    6-aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes mainly in the brainstem. We have examined the role of interleukin-6 (IL-6) in this degenerative process by using transgenic mice with astrocyte-targeted IL-6 expression (GFAP-IL6 mice). This s...

  17. Interindividual variation in the response by fibrinogen, C-reactive protein and interleukin-6 to yellow fever vaccination

    NARCIS (Netherlands)

    Verschuur, M.; Beek, M.T. van der; Tak, H.S.; Visser, L.G.; Maat, M.P.M. de

    2004-01-01

    The acute phase reaction is important in many disease processes. Habitual levels of the acute phase proteins fibrinogen, C-reactive protein (CRP) and interleukin-6 (IL-6) are associated with an increased risk of cardiovascular disease, but the dynamic variation of plasma levels of acute phase

  18. Serum Levels of Visfatin and Interleukin-6 in Non-Obese Versus Obese Men with Coronary Artery Disease

    International Nuclear Information System (INIS)

    Naz, S.; Sandhu, Q. S.; Akhtar, A.; Zafar, U.; Khalid, A.; Saeed, M.

    2017-01-01

    Objective: To evaluate and compare the serum levels of visfatin, interleukin-6 and lipid profile in non-obese and obese male patients with coronary artery disease. Study Design: Observational, comparative study. Place and Duration of Study: Punjab Institute of Cardiology and Lahore General Hospital, Lahore, from July to December 2013. Methodology: The participants included 20 non-obese group I with coronary artery disease (CAD) and 20 obese males group II with coronary artery disease (angiographically confirmed). All the participants were in the age group of 35 - 55 years being non-smokers and non-diabetic. Serum visfatin and interleukin-6 levels were analysed by Enzyme Linked Immunosorbent Assay (ELISA). Lipid profile was also evaluated. Results were compared with T-test and Mann Whitney U test. The values were considered significant at 0.05 level of significance. Results: Serum visfatin 9.05 versus 3.9 ng/ml and interleukin-6 12.80 versus 0.60 pg/ml levels were significantly (p-value < 0.001 of both) raised in the obese CAD group as compared to non-obese with CAD. Lipid profile also showed raised levels of total serum cholesterol, low density lipoproteins, triglycerides, very low density lipoproteins and low levels of high density lipoproteins in obese group. Conclusion: Significantly raised levels of serum visfatin and interleukin-6 indicate adipose tissue as an imperative source of these adipocytokines involved in inflammation in CAD. Altered lipid profile also seen in obese patients with CAD. (author)

  19. Interleukin-6 concentrations in the serum of patients with AIDS-associated Kaposi's sarcoma during treatment with interferon-alpha

    NARCIS (Netherlands)

    de Wit, R.; Raasveld, M. H.; ten Berge, R. J.; van der Wouw, P. A.; Bakker, P. J.; Veenhof, C. H.

    1991-01-01

    Interleukin-6 (IL-6) levels were determined in the serum of 14 HIV-1-infected patients with Kaposi's sarcoma, 10 HIV-1-infected patients without symptoms, and 10 healthy male subjects. IL-6 levels were also determined in the serum of the 14 patients with Kaposi's sarcoma during treatment with

  20. Kinetics of intraocular tumor necrosis factor and interleukin-6 in endotoxin-induced uveitis in the rat

    NARCIS (Netherlands)

    de Vos, A. F.; van Haren, M. A.; Verhagen, C.; Hoekzema, R.; Kijlstra, A.

    1994-01-01

    To determine the kinetics of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in serum and aqueous humor of rats with different susceptibilities to endotoxin-induced uveitis (EIU), after footpad injection of lipopolysaccharide (LPS). Samples were collected from EIU-susceptible Lewis rats and

  1. The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

    Directory of Open Access Journals (Sweden)

    Omoigui Sota

    2007-03-01

    Full Text Available Abstract We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.

  2. Posttranscriptional regulation of T-type Ca(2+) channel expression by interleukin-6 in prostate cancer cells.

    Science.gov (United States)

    Weaver, Erika M; Zamora, Francis J; Hearne, Jennifer L; Martin-Caraballo, Miguel

    2015-12-01

    At early stages, the growth of prostate cancers is androgen dependent. At later stages, however, the growth of prostate cancers becomes androgen independent, which leads to an increase in mortality. The switch to an androgen-refractory state is associated with neuroendocrine differentiation (NED) of prostate cancer cells. Several factors including interleukin-6 (IL-6) and increased cAMP production promote NED of prostate cancer cells. In this work we investigated whether IL-6 evoked NED of LNCaP cells results in a significant change in T-type Ca(2+) channel expression in comparison to non-stimulated LNCaP cells. T-type Ca(2+) channel subunit Cav3.2 expression was studied using PCR analysis, western blot and whole cell recordings. Tubulin IIIβ expression and neurite-like morphology was assessed to investigate the role of T-type Ca(2+) channels in the differentiation of prostate cancer cells. Treatment of LNCaP cells with IL-6 for 4days evokes considerable morphological and biochemical changes consistent with NED. Transcripts of the T-type Ca(2+) channel subunit Cav3.2 but not Cav3.1 or Cav3.3 are detected in IL-6 stimulated cells. Real time PCR analysis of IL-6 stimulated cells indicates no significant change in Cav3.2 mRNA expression in comparison to non-stimulated cells. LNCaP cells stimulated with IL-6 show a threefold increase in T-type Ca(2+) channel subunit Cav3.2 protein expression, suggesting that channel expression is upregulated by a posttranscriptional mechanism. Electrophysiological recordings reveal that increased Cav3.2 protein expression following IL-6 stimulation of LNCaP cells does not result in increased expression of functional channels in the membrane. Functional expression of Cav3.2 channels in LNCaP cells is facilitated by co-stimulation with IL-6 and the cAMP-stimulating agent, forskolin (FSK). Inhibition of T-type Ca(2+) channel activity in IL-6 stimulated LNCaP cells prevents the development of morphological characteristics consistent with

  3. IL-6 trans-signaling system in intra-amniotic inflammation, preterm birth, and preterm premature rupture of the membranes.

    Science.gov (United States)

    Lee, Sarah Y; Buhimschi, Irina A; Dulay, Antonette T; Ali, Unzila A; Zhao, Guomao; Abdel-Razeq, Sonya S; Bahtiyar, Mert O; Thung, Stephen F; Funai, Edmund F; Buhimschi, Catalin S

    2011-03-01

    Classic IL-6 signaling is conditioned by the transmembrane receptor (IL-6R) and homodimerization of gp130. During trans-signaling, IL-6 binds to soluble IL-6R (sIL-6R), enabling activation of cells expressing solely gp130. Soluble gp130 (sgp130) selectively inhibits IL-6 trans-signaling. To characterize amniotic fluid (AF) IL-6 trans-signaling molecules (IL-6, sIL-6R, sgp130) in normal gestations and pregnancies complicated by intra-amniotic inflammation (IAI), we studied 301 women during second trimester (n = 39), third trimester (n = 40), and preterm labor with intact (n = 131, 85 negative IAI and 46 positive IAI) or preterm premature rupture of membranes (PPROM; n = 91, 61 negative IAI and 30 positive IAI). ELISA, Western blotting, and real-time RT-PCR were used to investigate AF, placenta, and amniochorion for protein and mRNA expression of sIL-6R, sgp130, IL-6R, and gp130. Tissues were immunostained for IL-6R, gp130, CD15(+) (polymorphonuclear), and CD3(+) (T cell) inflammatory cells. The ability of sIL-6R and sgp130 to modulate basal and LPS-stimulated release of amniochorion matrix metalloprotease-9 was tested ex vivo. We showed that in physiologic gestations, AF sgp130 decreases toward term. AF IL-6 and sIL-6R were increased in IAI, whereas sgp130 was decreased in PPROM. Our results suggested that fetal membranes are the probable source of AF sIL-6R and sgp130. Immunohistochemistry and RT-PCR revealed increased IL-6R and decreased gp130 expression in amniochorion of women with IAI. Ex vivo, sIL-6R and LPS augmented amniochorion matrix metalloprotease-9 release, whereas sgp130 opposed this effect. We conclude that IL-6 trans-signaling molecules are physiologic constituents of the AF regulated by gestational age and inflammation. PPROM likely involves functional loss of sgp130.

  4. Expression of interleukin-6 by a recombinant rabies virus enhances its immunogenicity as a potential vaccine.

    Science.gov (United States)

    Luo, Jun; Zhang, Boyue; Wu, Yuting; Tian, Qin; Zhao, Jing; Lyu, Ziyu; Zhang, Qiong; Mei, Mingzhu; Luo, Yongwen; Guo, Xiaofeng

    2017-02-07

    Several studies have confirmed that interleukin-6 (IL6) mediates multiple biological effects that enhance immune responses when used as an adjuvant. In the present study, recombinant rabies virus (RABV) expressing canine IL6 (rHEP-CaIL6) was rescued and its pathogenicity and immunogenicity were investigated in mice. We demonstrated that mice received a single intramuscular immunization with rHEP-CaIL6 showed an earlier increase and higher maximum titres of virus-neutralizing antibody (VNA) as well as anti-RABV antibodies compared with mice immunized with the parent strain. Moreover, survival rates of mice immunized with rHEP-CaIL6 were higher compared with mice immunized with parent HEP-Flury according to the challenge assay. Flow cytometry further confirmed that immunization with rHEP-CaIL6 induced the strong recruitment of mature B cells and CD8 + T cells to lymph nodes, which may partially explain the high levels of VNA and enhanced cellular immunity. Quantitative real-time PCR indicated that rHEP-CaIL6 induced stronger inflammatory and immune responses in the central nervous system, which might have allowed virus clearance in the early infection phase. Furthermore, mice infected intranasally with rHEP-CaIL6 developed no clinical symptoms while mice infected with HEP-Flury showed piloerection. In summary, these data indicate that rHEP-CaIL6 induces a strong, protective immune response with a good safety profile. Therefore, a recombinant RABV strain expressing canine IL6 may aid the development of an effective, safe attenuated rabies vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.; Lin, Q.; Gao, H.B.; Zhang, P. [Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, Department of Biochemistry and Molecular Cell Biology, School of Medicine, Shanghai Jiao Tong University, Shanghai (China)

    2014-02-17

    In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.

  6. Venous thromboembolism, interleukin-6 and survival outcomes in patients with advanced ovarian clear cell carcinoma.

    Science.gov (United States)

    Matsuo, Koji; Hasegawa, Kosei; Yoshino, Kiyoshi; Murakami, Ryusuke; Hisamatsu, Takeshi; Stone, Rebecca L; Previs, Rebecca A; Hansen, Jean M; Ikeda, Yuji; Miyara, Akiko; Hiramatsu, Kosuke; Enomoto, Takayuki; Fujiwara, Keiichi; Matsumura, Noriomi; Konishi, Ikuo; Roman, Lynda D; Gabra, Hani; Fotopoulou, Christina; Sood, Anil K

    2015-09-01

    We compared survival outcomes and risk of venous thromboembolism (VTE) among patients with advanced and early-stage ovarian clear cell carcinoma (OCCC) and serous ovarian carcinoma (SOC), as well as potential links with interleukin-6 (IL-6) levels. A multicenter case-control study was conducted in 370 patients with OCCC and 938 with SOC. In a subset of 200 cases, pretreatment plasma IL-6 levels were examined. Patients with advanced OCCC had the highest 2-year cumulative VTE rates (advanced OCCC 43.1%, advanced SOC 16.2%, early-stage OCCC 11.9% and early-stage SOC 6.4%, P<0.0001) and the highest median levels of IL-6 (advanced OCCC 17.8 pg/mL, advanced SOC 9.0 pg/mL, early-stage OCCC 4.2 pg/mL and early-stage SOC 5.0 pg/mL, P=0.006). Advanced OCCC (hazard ratio [HR] 3.38, P<0.0001), thrombocytosis (HR 1.42, P=0.032) and elevated IL-6 (HR 8.90, P=0.046) were independent predictors of VTE. In multivariate analysis, patients with advanced OCCC had significantly poorer 5-year progression-free and overall survival rates than those with advanced SOC (P<0.01), and thrombocytosis was an independent predictor of decreased survival outcomes (P<0.01). Elevated IL-6 levels led to poorer 2-year progression-free survival rates in patients with OCCC (50% versus 87.5%, HR 4.89, P=0.016) than in those with SOC (24.9% versus 40.8%, HR 1.40, P=0.07). Advanced OCCC is associated with an increased incidence of VTE and decreased survival outcomes, which has major implications for clinical management of OCCC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Interleukin-6 Gene Promoter Polymorphisms and Cardiovascular Risk Factors. A family study

    Directory of Open Access Journals (Sweden)

    Iris Paola Guzmán-Guzmán

    2010-01-01

    Full Text Available Interleukin-6 (IL-6 is a cytokine involved in inflammatory process, as well as in glucose and lipid metabolism. Several studies of the biological relevance of IL-6 gene polymorphisms have indicated a relationship with cardiovascular disease. The aim of this study was to assess whether the –174 G/C and –572 G/C of IL-6 gene polymorphisms are associated with cardiovascular risk factors in Mexican families. Ninety members of 30 Mexican families, in which an index case (proband had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical and hematological parameters. High sensitivity C- reactive protein levels were measurement for nephelometric analysis. Screening for both polymorphisms studied was performed by PCR-RFLP. In the parents, both polymorphisms were in Hardy-Weinberg's equilibrium. The genotypes –174 GC/CC were associated with T2D (OR = 1.23, IC95% 1.01–1.5 and highest levels of hsCRP (p = 0.02, whereas genotype –572 GG was associated with T2D (OR = 1.24, IC95% 1.04–1.47 with an inflammatory state determined by the increase in the leukocyte count (OR = 1.24, IC95% 1.02–1.51. The genotypes –174 GC/CC and –572 GG may confer susceptibility for the development of subclinical inflammation and type 2 diabetes in Mexican families.

  8. Serum Interleukin-6, insulin, and HOMA-IR in male individuals with colorectal adenoma.

    Science.gov (United States)

    Sasaki, Yu; Takeda, Hiroaki; Sato, Takeshi; Orii, Tomohiko; Nishise, Shoichi; Nagino, Ko; Iwano, Daisuke; Yaoita, Takao; Yoshizawa, Kazuya; Saito, Hideki; Tanaka, Yasuhisa; Kawata, Sumio

    2012-01-15

    It is widely acknowledged that chronic low-grade inflammation plays a key role in the development of obesity-related insulin resistance and type 2 diabetes. The level of circulating interleukin-6 (IL-6), one of the major proinflammatory adipokines, is correlated with obesity and insulin resistance, which are known to be risk factors for colorectal adenoma. We examined the association between the circulating level of IL-6 and the presence of colorectal adenoma. In a total colonoscopy-based cross-sectional study conducted between January and December 2008, serum levels of IL-6 were measured in samples of venous blood obtained from 336 male participants attending health checkups (118 individuals with colorectal adenoma and 218 age-matched controls) after an overnight fast. In the colorectal adenoma group, the median levels of serum IL-6 (1.24 vs. 1.04 pg/mL; P = 0.01), triglyceride, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were to be significantly higher than those in the control group. When restricted to individuals with adenoma, levels of IL-6 were positively correlated with body mass index, insulin, and HOMA-IR. Multiple logistic analyses adjusted to include insulin or HOMA-IR showed that high levels of IL-6 were associated with the presence of colorectal adenoma. There was no significant interaction of IL-6 with HOMA-IR to modify this association. Our findings suggest that increased serum levels of IL-6 are positively associated with the presence of colorectal adenoma in men, independently of insulin and HOMA-IR. ©2011 AACR.

  9. Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Hiroto Kinoshita

    Full Text Available Interleukin-6 (IL-6 is a pleiotropic cytokine that affects various functions, including tumor development. Although the importance of IL-6 in gastric cancer has been documented in experimental and clinical studies, the mechanism by which IL-6 promotes gastric cancer remains unclear. In this study, we investigated the role of IL-6 in the epithelial-stromal interaction in gastric tumorigenesis. Immunohistochemical analysis of human gastritis, gastric adenoma, and gastric cancer tissues revealed that IL-6 was frequently detected in the stroma. IL-6-positive cells in the stroma showed positive staining for the fibroblast marker α-smooth muscle actin, suggesting that stromal fibroblasts produce IL-6. We compared IL-6 knockout (IL-6(-/- mice with wild-type (WT mice in a model of gastric tumorigenesis induced by the chemical carcinogen N-methyl-N-nitrosourea. The stromal fibroblasts expressed IL-6 in tumors from WT mice. Gastric tumorigenesis was attenuated in IL-6(-/- mice, compared with WT mice. Impaired tumor development in IL-6(-/- mice was correlated with the decreased activation of STAT3, a factor associated with gastric cancer cell proliferation. In vitro, when gastric cancer cell line was co-cultured with primary human gastric fibroblast, STAT3-related genes including COX-2 and iNOS were induced in gastric cancer cells and this response was attenuated with neutralizing anti-IL-6 receptor antibody. IL-6 production from fibroblasts was increased when fibroblasts were cultured in the presence of gastric cancer cell-conditioned media. IL-6 production from fibroblasts was suppressed by an interleukin-1 (IL-1 receptor antagonist and siRNA inhibition of IL-1α in the fibroblasts. IL-1α mRNA and protein were increased in fibroblast lysate, suggesting that cell-associated IL-1α in fibroblasts may be involved. Our results suggest the importance of IL-6 mediated stromal-epithelial cell interaction in gastric tumorigenesis.

  10. Role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice.

    Directory of Open Access Journals (Sweden)

    Karol Kaminski

    2011-04-01

    Full Text Available Postmenopausal women frequently develop hypothyroidism. Estrogen depletion is accompanied by an increase of IL-6, accelerating bone turnover. The influence of hypothyroidism on bone metabolism in postmenopausal women is poorly understood. The aim of the study was an attempt to clarify the role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT and C57BL/6JIL6-/-Kopf (IL-6 knock-out; IL6KO. The mice were randomly divided into 8 groups with 7 mice in each one: 1/ WT controls, 2/ IL6KO controls, 3/ WT hypothyroid mice, 4/ IL6KO hypothyroid mice, 5/ WT ovariectomized, 6/ IL6KO ovariectomized, 7/ WT ovariectomized hypothyroid mice and 8/ IL6KO ovariectomized hypothyroid mice. Experimental model of menopause was produced by bilateral ovariectomy carried out in 8-9 weeks old mice. Experimental model of hypothyroidism was induced by propylthiouracyl administration in driking water. The serum levels of TRACP 5b, osteocalcin, OPG and RANKL were determined by ELISA. Serum RANKL concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, but in a minor degree in IL6KO hypothyroid mice as compared to wild-type animals. Moreover sRANKL values were significantly lower in IL6KO as compared to WT controls and IL6KO PTU injected mice. Osteoprotegerin serum levels were decreased in all IL-6 deficient mice and in a highest degree in sham-operated hypothyroid mice. To sum up, the results of the present study suggest that estrogens deficit is a strong stimulus for RANKL-RANK/OPG pathway that breaks an inhibitory influence of hypothyroidism even in IL-6 deficient mice.

  11. Interleukin-6 is not essential for bone turnover in hypothyroid mice.

    Directory of Open Access Journals (Sweden)

    Maria Gorska

    2008-01-01

    Full Text Available Interleukin-6 (IL-6 has been shown to be involved in the pathogenesis of several bone diseases characterized by an imbalance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b and osteocalcin in IL-6-deficient mice to assess the role of IL-6 in bone metabolism in hypothyroidism in mice. C57BL/6J (wild-type; WT and C57BL/6J(IL6-/-Kopf (IL-6 knock-out; IL6KO mice randomly divided into 4 groups with 10 in each one: 1/ WT mice in hypothyroidism (WT-ht, 2/ WT controls, 3/ IL6KO mice with hypothyroidism (IL6KO-ht and 4/ IL6KO controls. Experimental model of hypothyroidism was induced by intraperitoneal injection of propylthiouracyl. The serum levels of TRACP 5b and osteocalcin were determined by ELISA. Serum concentrations of TRACP 5b (median and interquartile ranges were significantly decreased in both groups of mice with hypothyroidism: WT (3.2 (2.5-4.7 U/l and IL6KO (2.6 (1.8-3.5 U/l as compared to the respective controls. Similarly, serum osteocalcin levels were significantly reduced in both groups of mice in experimental hypothyroidism: WT (25.8 (23.0-28.2 ng/ml and IL6KO (21.5(19.0-24.6 ng/ml in comparison to the respective controls. There were no significant differences in bone turnover markers between IL6KO and WT mice both in hypothyroid and control animals. The results of the present study suggest that IL-6 does not play an important role in bone turnover in both euthyroid and hypothyroid mice.

  12. Motorcycle exhaust induces reproductive toxicity and testicular interleukin-6 in male rats.

    Science.gov (United States)

    Huang, Jing-Ying; Liao, Jiunn-Wang; Liu, Yi-Chun; Lu, Shui-Yuan; Chou, Chen-Ping; Chan, Wei-Hung; Chen, Shee-Uan; Ueng, Tzuu-Huei

    2008-05-01

    Motorcycle exhaust (ME) from two-stroke engines contains many toxicants and poses a potential health hazard. The major objectives of the present study were to investigate the male reproductive toxicity of ME and the underlying mechanisms of toxicity. Male Wistar rats were exposed to ME by inhalation 1 h each in the morning and afternoon, Monday through Friday. Exposures to 1:50 diluted ME for 4 weeks or to 1:10 diluted ME for 2 and 4 weeks showed concentration- and time-dependent decreases of testicular weight, spermatid number, and cauda epididymal sperm number. Subsequent studies were done using 4-week exposure to 1:10 diluted ME. ME caused histopathological changes including testicular spermatocytic necrosis and seminiferous tubule atrophy and cauda epididymal formation of clusters of pyknotic and necrotic sperm cells. ME-exposed male rats mated with untreated females showed decreases of male mating index and female fertility index and an increase of implantation site loss. ME decreased 7-ethoxycoumarin O-deethylase and superoxide dismutase activities but induced proinflammatory cytokine interleukin-6 (IL-6) messenger RNA (mRNA) in the testis. Male rats were exposed to ME with or without cotreatment with 50 mg/kg vitamin E orally for 4 weeks. ME decreased serum testosterone concentration. This effect was reversed by cotreatment with vitamin E. ME decreased testicular spermatid number and induced IL-6 mRNA and protein. These effects were also reversed by the vitamin E cotreatment. The present findings show that ME causes male reproductive effects and induces testicular IL-6 in rats by mechanisms involving induction of oxidative stress and inhibition of steroidogenesis.

  13. Meta-analysis of interleukin-6 concentration in peritoneal fluid of women with endometriosis

    International Nuclear Information System (INIS)

    Zuo Liandong; Zheng Hui; Li Hongyi

    2003-01-01

    To investigate whether the Interleukin-6 (IL-6) concentration in peritoneal fluid of patients with endometriosis (EM) is higher than that of healthy, synthetic quantitative analysis was used to study international literatures on IL-6 in peritoneal fluid of women with EM by means of Meta-analysis. The results showed that IL-6 levels of ELISA in the women with EM were -0.472-3.974 times of standard deviation higher than those in the healthy control group. Regardless of measurement methods, -0.73-3.45 times of standard deviation was higher. Both results could not generally think that the IL-6 in peritoneal fluid of EM patient was higher than that of normal persons. However, when EM was diagnosed at the time of laparoscopy or surgery and staged according to AFS, I-II stage were attributed to EM1, III-IV stage were EM2. It was found by Meta-analysis that the elevated IL-6 levels had a mutual relation with the severity of EM: The levels of EM1 were -4.807-5.608 times of standard deviation higher than those of then healthy, with no significant difference (P>0.05), whereas those of EM2 were 0.54-5.34 times or 1.13-5.46 times of standard deviation higher than those of EM1 or healthy, respectively, both with significant difference. The higher the IL-6 levels of the patients had in peritoneal fluid, the more serious EM were. The dysregulation of IL-6 responses might play a role in the pathophysiology of EM

  14. Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression

    Energy Technology Data Exchange (ETDEWEB)

    Patchen, M.L.; MacVittie, T.J.; Williams, J.L.; Schwartz, G.N.; Souza, L.M. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1991-02-01

    Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL-6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline-treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.

  15. Discovery and Characterization of a Potent Interleukin-6 Binding Peptide with Neutralizing Activity In Vivo.

    Directory of Open Access Journals (Sweden)

    Sheila Ranganath

    Full Text Available Interleukin-6 (IL-6 is an important member of the cytokine superfamily, exerting pleiotropic actions on many physiological processes. Over-production of IL-6 is a hallmark of immune-mediated inflammatory diseases such as Castleman's Disease (CD and rheumatoid arthritis (RA. Antagonism of the interleukin IL-6/IL-6 receptor (IL-6R/gp130 signaling complex continues to show promise as a therapeutic target. Monoclonal antibodies (mAbs directed against components of this complex have been approved as therapeutics for both CD and RA. To potentially provide an additional modality to antagonize IL-6 induced pathophysiology, a peptide-based antagonist approach was undertaken. Using a combination of molecular design, phage-display, and medicinal chemistry, disulfide-rich peptides (DRPs directed against IL-6 were developed with low nanomolar potency in inhibiting IL-6-induced pSTAT3 in U937 monocytic cells. Targeted PEGylation of IL-6 binding peptides resulted in molecules that retained their potency against IL-6 and had a prolongation of their pharmacokinetic (PK profiles in rodents and monkeys. One such peptide, PN-2921, contained a 40 kDa polyethylene glycol (PEG moiety and inhibited IL-6-induced pSTAT3 in U937 cells with sub-nM potency and possessed 23, 36, and 59 h PK half-life values in mice, rats, and cynomolgus monkeys, respectively. Parenteral administration of PN-2921 to mice and cynomolgus monkeys potently inhibited IL-6-induced biomarker responses, with significant reductions in the acute inflammatory phase proteins, serum amyloid A (SAA and C-reactive protein (CRP. This potent, PEGylated IL-6 binding peptide offers a new approach to antagonize IL-6-induced signaling and associated pathophysiology.

  16. Anorexia, fatigue, and plasma interleukin-6 levels in chronic hemodialysis patients.

    Science.gov (United States)

    Bossola, Maurizio; Luciani, Giovanna; Giungi, Stefania; Tazza, Luigi

    2010-01-01

    This study aimed at evaluating the possible relationship between anorexia and fatigue in hemodialysis (HD) patients and at measuring the plasma levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in HD patients with or without anorexia and/or fatigue. The first question of the Hemodialysis Study Appetite questionnaire was used to assess the appetite of the HD patients and the vitality scale of the SF-36 to assess fatigue. The Charlson Comorbidity Index was assessed in each patient. Seventy-six HD patients were studied. Forty-four were males and 32 females. Thirty-two were classified as not-anorexic and not-fatigued, 12 as not-anorexic but fatigued, 6 as anorexic and not-fatigued, and 26 as anorexic and fatigued. Plasma IL-6 levels (pg/mL) were significantly higher in anorexic and fatigued patients (10.9 ± 11.9) than in not-anorexic and not-fatigued (1.6 ± 0.6) (p anorexic but not-fatigued patients (1.8 ± 1.7) (p anorexic but fatigued patients (3.1 ± 1.5), the difference was not statistically significant (p = 0.058). The plasma CRP levels (mg/dL) also were significantly higher in anorexic and fatigued patients (9.2 ± 6.3) than in not-anorexic and not-fatigued patients (4.1 ± 4.5), in anorexic but not-fatigued patients (2.5 ± 1.6), and in not-anorexic but fatigued patients (4.1 ± 4.4) (p = 0.001). The presence of both anorexia and fatigue in chronic HD patients is associated with significantly higher levels of plasma IL-6 and CRP and a higher frequency of comorbidities.

  17. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice

    Directory of Open Access Journals (Sweden)

    Izziki Mohamed

    2009-01-01

    Full Text Available Abstract Background Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH. Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6. Methods To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6-/- and wild-type (IL-6+/+ mice exposed to hypoxia for 2 weeks. Results Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6-/- mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6+/+ and IL-6-/- mice. Hypoxia exposure of IL-6+/+ mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6-/- mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines. Conclusion These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.

  18. Interleukin-6 and interleukin-10 plasma levels and mRNA expression in polytrauma patients.

    Science.gov (United States)

    Sapan, Heber B; Paturusi, Idrus; Islam, Andi Asadul; Yusuf, Irawan; Patellongi, Ilhamjaya; Massi, Muhammmad Nasrum; Pusponegoro, Aryono D; Arief, Syafrie K; Labeda, Ibrahim; Rendy, Leo; Hatta, Mochammad

    2017-12-01

    Host response to polytrauma occasionally has unpredictable outcomes. Immune response is a major factor influencing patient's outcome. This study evaluated the interaction of two main cytokines in immune response after major trauma, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10). Plasma level of these cytokines is determined by mRNA expression of these cytokines genes which may decide the outcome of polytrauma patients. This prospective multicenter trial held at four trauma centers enrolled 54 polytrauma patients [Injury Severity Score (ISS) ≥ 16]. Plasma levels and mRNA expression of IL-6 and IL-10 were measured for 5 days after trauma. Clinical evaluation was conducted to observe whether patients endured multiple organ dysfunction syndrome (MODS) and death. MODS evaluation was performed using sequential organ failure assessment (SOFA). Trauma load which in this study is represented with ISS, plasma level, expression of cytokine genes and patient's outcome were examined with correlation test and statistical analysis. The elevated IL-6/IL-10 ratio indicated increased activity of systemic inflammation response, especially pro-inflammation response which bears higher probability of progressing to MODS and death. The decline of IL-6/IL-10 ratio with heavy trauma load (ISS > 30) showed that compensatory anti-inflammation response syndrome (CARS) state was more dominant than systemic inflammatory response syndrome (SIRS), indicating that malfunction and failure of immune system eventually lead to MODS and deaths. The statistical significance in plasma level of cytokines was found in the outcome group which was defined as bearing a low trauma load but mortality. The pattern of cytokine levels in inflammation response has great impact on the outcome of polytrauma patients. Further study at the genetic level is needed to investigate inflammation process which may influence patient's outcome. Copyright © 2017 Daping Hospital and the Research Institute of

  19. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Association of maternal and neonatal plasma interleukin-6 levels in relation to model of delivery

    Directory of Open Access Journals (Sweden)

    Mahmoud Imani

    2011-07-01

    Full Text Available Background: Cytokines play an important role during labor of full – or pretern delivery. In umbilical cord blood, Interleukin-6 (IL-6 was thought to be a marker of defense to stress, surgery and infection. The aim of this study was to investigate the cytokine IL-6 concentrations in the mother and neonate depends on the mode of the delivery.Materials and Method: This study was done on mothers and neonates in 80 single term deliveries (vaginal and cesarean in Mahdieh Hospital in Tehran. Age of mothers was 21-39 years old, parity was 1 and 2. There wasn't history of underlying disease and drug usage in mothers and neonate was AGA and apgar was more than 8. There wasn't clinical evidence of infection in neonate and mothers. IL-6 was evaluated by enzyme-immunoassays in maternal serum and neonatal umbilical cord. Data were analyzed with SPSS and were applied fishers exact test for compare means.Results: There were 37 vaginal deliveries and 43cesarean section. The mean (±standard error of maternal IL-6 concentration in vaginal delivery (0.18±0.02 was significantly (P=0.000 higher than cesarean section (0.1±0.02 and neonatal IL-6 concentration in vaginal delivery (0.17±0.03 was significantly (P=0.000 higher than cesarean section (0.07±0.01.Conclusion: Results show that vaginal delivery cause to increase IL-6 compared to cesarean section in mother and neonate

  1. A novel T cell cytokine stimulates interleukin-6 in human osteoblastic cells.

    Science.gov (United States)

    Rifas, L; Avioli, L V

    1999-07-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by a heavy lymphocytic infiltration into the synovial cavity, resulting in the secretion of a variety of cytokines which ultimately leads to destruction of joint tissue. Among the infiltrating cells are activated T cells which produce specific cytokines capable of osteoclast progenitor cell expansion, fusion, and activation. Cultures of activated human T cells and human osteoblasts (hOBs) were used to study the possibility that lymphokines may act on osteoblasts to produce the osteoclastogenic factor interleukin-6 (IL-6). Purified T cells were activated with a combination of anti-CD3 and anti-CD28 antibodies, cocultured with hOBs in direct physical contact or separated by a transwell system, and conditioned media (CM) were assayed for IL-6 production. After a 72 h incubation period, activated T cell-hOB interaction resulted in a 100-fold increase of IL-6 production over basal levels. The immunosuppressant cyclosporine A (CsA) inhibited T cell tumor necrosis factor alpha and IL-6 production but did not inhibit the T cell induction of IL-6 from hOB. Assay of activated T-cell CM on hOB revealed that a soluble factor, not cell-cell contact, was the major inducer of IL-6. The induction of IL-6 mRNA by both activated T cell CM and CsA-treated activated T cell CM was confirmed by Northern blot analysis. Neutralizing antibodies to IL-13 and IL-17 did not affect IL-6 production. These findings suggest that activated T cells produce a novel, potent, IL-6 inducing factor that may be responsible for the bone loss observed in RA patients.

  2. Role of interleukin-6 levels in cardiovascular autonomic dysfunction in type 2 diabetic patients

    Energy Technology Data Exchange (ETDEWEB)

    Shinohara, Tetsuji; Takahashi, Naohiko; Kakuma, Tetsuya; Hara, Masahide; Yoshimatsu, Hironobu [Oita University, Department of Internal Medicine 1, Faculty of Medicine, Yuhu, Oita (Japan); Yufu, Kunio; Anan, Futoshi; Nakagawa, Mikiko; Saikawa, Tetsunori [Oita University, Department of Cardiovascular Science, Oita (Japan)

    2008-09-15

    Increased serum interleukin-6 (IL-6) levels are associated with an increased risk of cardiovascular disease, and cardiovascular autonomic dysfunction is associated with high mortality in type 2 diabetic patients. However, the relationship between IL-6 levels and cardiovascular autonomic dysfunction has not been fully elucidated. The aim of this study was to determine whether serum IL-6 levels are associated with cardiovascular autonomic dysfunction in type 2 diabetic patients. Eighty type 2 diabetic patients who did not have organic heart disease were categorized into a high IL-6 group (>2.5 pg/ml, n= 0, age 59{+-}12 years) or a non-high IL-6 group (<2.5 pg/ml, n=40, 61{+-}12 years). Cardiac autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations and {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. The body mass index values (BMI), fasting insulin levels and homeostasis model assessment index values were higher in the high IL-6 group than in the non-high IL-6 group (p<0.01). Early and delayed {sup 123}I-MIBG myocardial uptake values were lower (p<0.01), and the percent washout rate of {sup 123}I-MIBG was higher (p<0.05) in the high IL-6 group than in the non-high IL-6 group. Furthermore, multiple regression analysis revealed that the IL-6 level was independently predicted by the BMI and the myocardial uptake of {sup 123}I-MIBG during the delayed phase. The results indicate that elevated IL-6 levels are associated with depressed cardiovascular autonomic function and obesity in type 2 diabetic patients. (orig.)

  3. Interleukin-6 maintains glucose homeostasis to support strenuous masseter muscle activity in mice.

    Science.gov (United States)

    Tsuchiya, Masahiro; Kiyama, Tomomi; Tsuchiya, Shinobu; Takano, Hirohisa; Nemoto, Eiji; Sasaki, Keiichi; Watanabe, Makoto; Sugawara, Shunji; Endo, Yasuo

    2012-06-01

    The cytokine interleukin-6 (IL-6) is released from working skeletal muscles and reportedly plays key roles in their glucose homeostasis. However, it is unclear whether IL-6 plays such roles in the masseter muscle (MM), which is important in normal and pathological chewing behaviors, such as bruxism and/or prolonged clenching. When restrained (R+) in a narrow cylinder blocked at the front end with a thin plastic strip, a mouse gnaws away (G+) the strip to escape. The absolute weight of plastic gnawed away serves as an index of MM activity. Using this model, we examined the roles of IL-6 in MM with the following results. R+G+ increased the expression levels of IL-6 and glucose transporter 4 (Glut4) mRNAs in MM and the serum level of IL-6 protein. IL-6-deficient mice exhibited about 60% less gnawing activity than wild-type mice at 3-4 h after the start of R+G+, slower recovery of glycogen levels (indicating poorer glucose supply) in MM after R+G+, and no significant change in Glut4 mRNA in MM upon R+G+. During an R+G+ test conducted after "training" (repeated R+G+ sessions), wild-type mice exhibited greater gnawing activity than untrained controls, but no increase in IL-6 mRNA in MM. IL-6 mRNA increased in MM when hard food was eaten by mice raised on soft food for 3 weeks from weaning, but not in those raised on (accustomed to) hard food. Thus, IL-6 may maintain glucose homeostasis in MM in support of unusually strenuous activity, but not of accustomed activity levels.

  4. Inhibition of interleukin-6 expression by the V protein of parainfluenza virus 5

    International Nuclear Information System (INIS)

    Lin Yuan; Sun Minghao; Fuentes, Sandra M.; Keim, Celia D.; Rothermel, Terri; He Biao

    2007-01-01

    The V protein of parainfluenza virus 5 (PIV5) plays an important role in the evasion of host immune responses. The V protein blocks interferon (IFN) signaling in human cells by causing degradation of the STAT1 protein, a key component of IFN signaling, and blocks IFN-β production by preventing nuclear translocation of IRF3, a key transcription factor for activating IFN-β promoter. Interleukin-6 (IL-6), along with tumor necrosis factor (TNF)-α and IL-1β, is a major proinflammatory cytokine that plays important roles in clearing virus infection through inflammatory responses. Many viruses have developed strategies to block IL-6 expression. Wild-type PIV5 infection induces little, if any, expression of cytokines such as IL-6 or TNF-α, whereas infection by a mutant PIV5 lacking the conserved C-terminal cysteine rich domain (rPIV5VΔC) induced high levels of IL-6 expression. Examination of mRNA levels of IL-6 indicated that the transcription activation of IL-6 played an important role in the increased IL-6 expression. Co-infection with wild-type PIV5 prevented the activation of IL-6 transcription by rPIV5VΔC, and a plasmid encoding the full-length PIV5 V protein prevented the activation of IL-6 promoter-driven reporter gene expression by rPIV5VΔC, indicating that the V protein played a role in inhibiting IL-6 transcription. The activation of IL-6 was independent of IFN-β even though rPIV5VΔC-infected cells produced IFN-β. Using reporter gene assays and chromatin immunoprecipitation (ChIP), it was found that NF-κB played an important role in activating expression of IL-6. We have proposed a model of activating and inhibiting IL-6 transcription by PIV5

  5. Discovery and Characterization of a Potent Interleukin-6 Binding Peptide with Neutralizing Activity In Vivo

    Science.gov (United States)

    Ranganath, Sheila; Bhandari, Ashok; Avitahl-Curtis, Nicole; McMahon, Jaimee; Wachtel, Derek; Zhang, Jenny; Leitheiser, Christopher; Bernier, Sylvie G.; Liu, Guang; Tran, Tran T.; Celino, Herodion; Tobin, Jenny; Jung, Joon; Zhao, Hong; Glen, Katie E.; Graul, Chris; Griffin, Aliesha; Schairer, Wayne C.; Higgins, Carolyn; Reza, Tammi L.; Mowe, Eva; Rivers, Sam; Scott, Sonya; Monreal, Alex; Shea, Courtney; Bourne, Greg; Coons, Casey; Smith, Adaline; Tang, Kim; Mandyam, Ramya A.; Masferrer, Jaime; Liu, David; Patel, Dinesh V.; Fretzen, Angelika; Murphy, Craig A.; Milne, G. Todd; Smythe, Mark L.; Carlson, Kenneth E.

    2015-01-01

    Interleukin-6 (IL-6) is an important member of the cytokine superfamily, exerting pleiotropic actions on many physiological processes. Over-production of IL-6 is a hallmark of immune-mediated inflammatory diseases such as Castleman’s Disease (CD) and rheumatoid arthritis (RA). Antagonism of the interleukin IL-6/IL-6 receptor (IL-6R)/gp130 signaling complex continues to show promise as a therapeutic target. Monoclonal antibodies (mAbs) directed against components of this complex have been approved as therapeutics for both CD and RA. To potentially provide an additional modality to antagonize IL-6 induced pathophysiology, a peptide-based antagonist approach was undertaken. Using a combination of molecular design, phage-display, and medicinal chemistry, disulfide-rich peptides (DRPs) directed against IL-6 were developed with low nanomolar potency in inhibiting IL-6-induced pSTAT3 in U937 monocytic cells. Targeted PEGylation of IL-6 binding peptides resulted in molecules that retained their potency against IL-6 and had a prolongation of their pharmacokinetic (PK) profiles in rodents and monkeys. One such peptide, PN-2921, contained a 40 kDa polyethylene glycol (PEG) moiety and inhibited IL-6-induced pSTAT3 in U937 cells with sub-nM potency and possessed 23, 36, and 59 h PK half-life values in mice, rats, and cynomolgus monkeys, respectively. Parenteral administration of PN-2921 to mice and cynomolgus monkeys potently inhibited IL-6-induced biomarker responses, with significant reductions in the acute inflammatory phase proteins, serum amyloid A (SAA) and C-reactive protein (CRP). This potent, PEGylated IL-6 binding peptide offers a new approach to antagonize IL-6-induced signaling and associated pathophysiology. PMID:26555695

  6. Cardiovascular Response and Serum Interleukin-6 Level in Concentric Vs. Eccentric Exercise.

    Science.gov (United States)

    Agarwal, Mayank; Singh, Shraddha; Narayan, Jagdish; Pandey, Shivani; Tiwari, Sunita; Sharma, Priyanka

    2017-04-01

    Cardiovascular Disease (CVD) is a leading cause of morbidity and mortality in India. Resistance exercise is strongly recommended for implementation in CVD prevention programs. Dynamic resistance exercise comprises of concentric (muscle shortening) and eccentric (muscle lengthening) phase. The contraction of skeletal muscle promotes the synthesis and secretion of cytokines and peptides from myocytes, known as 'myokines'. Interleukin-6 (IL-6) is the first myokine to be released in the blood in response to exercise. To compare the cardiovascular response and serum IL-6 level in concentric and eccentric exercise done at same absolute workload. In this non-randomised crossover study 24, apparently healthy and young male adults performed an acute bout of concentric and eccentric exercise. Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Heart Rate (HR), Mean Arterial Pressure (MAP), Pulse Pressure (PP) and serum IL-6 were measured just before and immediately after exercise. Paired t-test or Wilcoxon signed-rank test were applied to compare the data within-group and in-between group. SBP, HR, MAP, PP, DBP and IL-6 level increased significantly after both, concentric and eccentric exercise. The mean change in SBP, HR, MAP, PP, and IL-6 after concentric exercise (18.54±3.06, 57.21±10.73, 8.35±1.40, 15.25±5.29, 5.40±3.13 respectively) was significantly higher than after eccentric exercise (13.38±1.72, 43.25±8.34, 6.50±1.0, 10.21±3.16, 4.36±2.54 respectively). A non-significant rise in DBP was obtained after concentric exercise (3.25±2.79) as compared to eccentric exercise (3.08±1.89). Eccentric exercise not only caused a lesser cardiovascular demand as compared to concentric exercise but also a significant increment in IL-6 level. Exercise-induced IL-6 may prevent the initiation and development of CVD. Hence, eccentric exercise training might be recommended for reducing morbidity and mortality in individuals with- or at a risk of developing CVD.

  7. Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy.

    Science.gov (United States)

    Ptaszynska-Kopczynska, Katarzyna; Szpakowicz, Anna; Marcinkiewicz-Siemion, Marta; Lisowska, Anna; Waszkiewicz, Ewa; Witkowski, Marcin; Jakim, Piotr; Galar, Bogdan; Musial, Wlodzimierz J; Kamiński, Karol A

    2017-08-01

    Increased expression of interleukin-6 (IL-6) has been described in left ventricular dysfunction in the course of chronic heart failure. Cardiac resynchronization therapy (CRT) is a unique treatment method that may reverse the course of chronic heart failure (CHF) with reduced ejection fraction (HF-REF). We aimed to evaluate the IL-6 system, including soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130), in HF-REF patients, with particular emphasis on CRT effects. The study enrolled 88 stable HF-REF patients (63.6 ±11.1 years, 12 females, EF < 35%) and 35 comorbidity-matched controls (63.5 ±9.8 years, 7 females). Forty-five HF-REF patients underwent CRT device implantation and were followed up after 6 months. Serum concentrations of IL-6, sIL-6R and sgp130 were determined using ELISA kits. The HF-REF patients had higher IL-6 (median: 2.6, IQR: 1.6-3.8 vs. 2.1, IQR: 1.4-3.1 pg/ml, p = 0.03) and lower sIL-6R concentrations compared to controls (median: 51, IQR: 36-64 vs. 53. IQR 44-76 ng/ml, p = 0.008). There was no significant difference between sgp130 concentrations. In the HF-REF group IL-6 correlated negatively with EF ( r = -0.5, p = 0.001) and positively with BNP ( r = 0.5, p = 0.008) and CRP concentrations ( r = 0.4, p = 0.02). Patients who presented a positive response after CRT showed a smaller change of sIL-6R concentration compared to nonresponders (ΔsIL-6R: -0.2 ±7.1 vs. 7 ±14 ng/ml; p = 0.04). HF-REF patients present higher IL-6 and lower sIL-6R levels. IL-6 concentration reflects their clinical status. CRT-related improvement of patients' functional status is associated with a smaller change of sIL-6R concentration in time.

  8. Interleukin-6 and airflow limitation in chemical warfare patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Davood Attaran

    2010-09-01

    disease, interleukin-6, inflammation, chemical warfare

  9. Interleukin-6 Attenuates Serotonin 2A Receptor Signaling by Activating the JAK-STAT Pathway

    Science.gov (United States)

    Donegan, Jennifer J.; Patton, Michael S.; Chavera, Teresa S.; Berg, Kelly A.; Morilak, David A.

    2015-01-01

    The serotonin 2A (5-HT2A) receptor and the proinflammatory cytokine, interleukin-6 (IL-6), have both been implicated in psychiatric disorders. Previously, we demonstrated that these molecules both facilitate cognitive flexibility, a prefrontal cortex-mediated executive function impaired in multiple mental illnesses. In this study, we tested the hypothesis that IL-6 influences 5-HT2A receptor signaling, providing a potential mechanism by which this cytokine may influence behavior. We first demonstrated that 5-HT2A receptors and IL-6–mediated STAT3 phosphorylation colocalize in cells of the prefrontal cortex, providing the neuroanatomical substrate for a potential interaction. In the neuronally derived A1A1 cell line, which expresses both IL-6 and 5-HT2A receptors, we found that IL-6 attenuates inositol phosphate (IP) accumulation in response to the 5-HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), suggesting that IL-6 can regulate 5-HT2A receptor function. To identify the signaling pathway(s) that mediate this effect, we measured DOI-mediated IP accumulation in the presence of IL-6 and either the JAK-STAT inhibitor 124 [(9β,10α,16α,23E)-2,16,20,25-tetrahydroxy-9-methyl-19-norlanosta-1,5,23-triene-3,11,22-trione], JSI-124, or the extracellular signal-regulated kinase inhibitor, 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD-98059). The IL-6 effect was blocked by JSI-124 but not PD-98059. Furthermore, silencing RNA knockdown of either JAK or STAT blocked the IL-6 effect, suggesting that IL-6–induced JAK-STAT activation can regulate 5-HT2A receptor signaling. Finally, to determine if IL-6 specifically regulates the 5-HT2A receptor system, we measured IP production mediated by another Gq-coupled receptor, bradykinin B2. IL-6 had no effect on bradykinin-mediated IP accumulation, suggesting that regulation may occur at the 5-HT2A receptor. These results may provide clues to the pathologic mechanisms underlying certain psychiatric disorders and may

  10. Interleukin 6 Deficiency Modulates the Hypothalamic Expression of Energy Balance Regulating Peptides during Pregnancy in Mice

    Science.gov (United States)

    Pazos, Patricia; Lima, Luis; Casanueva, Felipe F.; Diéguez, Carlos; García, María C.

    2013-01-01

    Pregnancy is associated with hyperphagia, increased adiposity and multiple neuroendocrine adaptations. Maternal adipose tissue secretes rising amounts of interleukin 6 (IL6), which acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. To explore the role of IL6 in the central mechanisms governing dam's energy homeostasis, early, mid and late pregnant (gestational days 7, 13 and 18) wild-type (WT) and Il6 knockout mice (Il6-KO) were compared with virgin controls at diestrus. Food intake, body weight and composition as well as indirect calorimetry measurements were performed in vivo. Anabolic and orexigenic peptides: neuropeptide Y (Npy) and agouti-related peptide (Agrp); and catabolic and anorectic neuropeptides: proopiomelanocortin (Pomc), corticotrophin and thyrotropin-releasing hormone (Crh and Trh) mRNA levels were determined by in situ hybridization. Real time-PCR and western-blot were used for additional tissue gene expression and protein studies. Non-pregnant Il6-KO mice were leaner than WT mice due to a decrease in fat but not in lean body mass. Pregnant Il6-KO mice had higher fat accretion despite similar body weight gain than WT controls. A decreased fat utilization in absence of Il6 might explain this effect, as shown by increased respiratory exchange ratio (RER) in virgin Il6-KO mice. Il6 mRNA levels were markedly enhanced in adipose tissue but reduced in hypothalamus of mid and late pregnant WT mice. Trh expression was also stimulated at gestational day 13 and lack of Il6 blunted this effect. Conversely, in late pregnant mice lessened hypothalamic Il6 receptor alpha (Il6ra), Pomc and Crh mRNA were observed. Il6 deficiency during this stage up-regulated Npy and Agrp expression, while restoring Pomc mRNA levels to virgin values. Together these results demonstrate that IL6/IL6Ra system modulates Npy/Agrp, Pomc and Trh expression during mouse pregnancy, supporting a role of IL6 in the central

  11. Interleukin 6 deficiency modulates the hypothalamic expression of energy balance regulating peptides during pregnancy in mice.

    Science.gov (United States)

    Pazos, Patricia; Lima, Luis; Casanueva, Felipe F; Diéguez, Carlos; García, María C

    2013-01-01

    Pregnancy is associated with hyperphagia, increased adiposity and multiple neuroendocrine adaptations. Maternal adipose tissue secretes rising amounts of interleukin 6 (IL6), which acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. To explore the role of IL6 in the central mechanisms governing dam's energy homeostasis, early, mid and late pregnant (gestational days 7, 13 and 18) wild-type (WT) and Il6 knockout mice (Il6-KO) were compared with virgin controls at diestrus. Food intake, body weight and composition as well as indirect calorimetry measurements were performed in vivo. Anabolic and orexigenic peptides: neuropeptide Y (Npy) and agouti-related peptide (Agrp); and catabolic and anorectic neuropeptides: proopiomelanocortin (Pomc), corticotrophin and thyrotropin-releasing hormone (Crh and Trh) mRNA levels were determined by in situ hybridization. Real time-PCR and western-blot were used for additional tissue gene expression and protein studies. Non-pregnant Il6-KO mice were leaner than WT mice due to a decrease in fat but not in lean body mass. Pregnant Il6-KO mice had higher fat accretion despite similar body weight gain than WT controls. A decreased fat utilization in absence of Il6 might explain this effect, as shown by increased respiratory exchange ratio (RER) in virgin Il6-KO mice. Il6 mRNA levels were markedly enhanced in adipose tissue but reduced in hypothalamus of mid and late pregnant WT mice. Trh expression was also stimulated at gestational day 13 and lack of Il6 blunted this effect. Conversely, in late pregnant mice lessened hypothalamic Il6 receptor alpha (Il6ra), Pomc and Crh mRNA were observed. Il6 deficiency during this stage up-regulated Npy and Agrp expression, while restoring Pomc mRNA levels to virgin values. Together these results demonstrate that IL6/IL6Ra system modulates Npy/Agrp, Pomc and Trh expression during mouse pregnancy, supporting a role of IL6 in the central

  12. Low-Dose Pulsatile Interleukin-6 As a Treatment Option for Diabetic Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Gautam Ghatnekar

    2017-05-01

    Full Text Available Diabetic peripheral neuropathy (DPN remains one of the most common and serious complications of diabetes. Currently, pharmacological agents are limited to treating the pain associated with DPN, and do not address the underlying pathological mechanisms driving nerve damage, thus leaving a significant unmet medical need. Interestingly, research conducted using exercise as a treatment for DPN has revealed interleukin-6 (IL-6 signaling to be associated with many positive benefits such as enhanced blood flow and lipid metabolism, decreased chronic inflammation, and peripheral nerve fiber regeneration. IL-6, once known solely as a pro-inflammatory cytokine, is now understood to signal as a multifunctional cytokine, capable of eliciting both pro- and anti-inflammatory responses in a context-dependent fashion. IL-6 released from muscle in response to exercise signals as a myokine and as such has a unique kinetic profile, whereby levels are transiently elevated up to 100-fold and return to baseline levels within 4 h. Importantly, this kinetic profile is in stark contrast to long-term IL-6 elevation that is associated with pro-inflammatory states. Given exercise induces IL-6 myokine signaling, and exercise has been shown to elicit numerous beneficial effects for the treatment of DPN, a causal link has been suggested. Here, we discuss both the clinical and preclinical literature related to the application of IL-6 as a treatment strategy for DPN. In addition, we discuss how IL-6 may directly modulate Schwann and nerve cells to explore a mechanistic understanding of how this treatment elicits a neuroprotective and/or regenerative response. Collectively, studies suggest that IL-6, when administered in a low-dose pulsatile strategy to mimic the body’s natural response to exercise, may prove to be an effective treatment for the protection and/or restoration of peripheral nerve function in DPN. This review highlights the studies supporting this assertion and

  13. Interleukin 6 and lipopolysaccharide binding protein - markers of inflammation in acute appendicitis.

    Science.gov (United States)

    Brănescu, C; Serban, D; Dascălu, A M; Oprescu, S M; Savlovschi, C

    2013-01-01

    The rate of incidence of acute appendicitis is 12% in the case of male patients and 25% in case of women, which represents about 7% of the world population. The appendectomy rate has remained constant (i.e. 10 out of 10,000 patients per year). Appendicitis most often occurs in patients aged between 11-40 years, on the threshold between the third and fourth decades, the average age being 31.3 years. Since the first appendectomy performed by Claudius Amyand (1681/6 -1740), on December, 6th, 1735 to our days, i.e., 270 years later, time has confirmed the efficiency of both the therapy method and the surgical solution. The surgical cure in case of acute appendicitis has proved to be acceptable within the most widely practised techniques in general surgery. The variety of clinical forms has reached all age ranges, which in its turn has resulted in a large number of semiotic signs. In the case of acute appendicitis, interdisciplinarity has allowed the transfer of concept and methodology transfer among many areas of expertise, aimed at a better, minute understanding of the inflammatory event itself. Acute appendicitis illustrates inflammation development at digestive level and provides for a diagnostic and paraclinical exploration which continually upgrades. The recent inclusion in the studies of the Lipopolysaccharide binding protein (LBP)- type inflammation markers has laid the foundation of the latter's documented presence in the case of acute appendicitis-related inflammation. Proof of the correlation between the histopathological, clinical and evolutive forms can be found by identifying and quantifying these inflammation markers. The importance of studying inflammation markers allows us to conduct studies going beyond the prognosis of the various stages in which these markers were identified. The present article shows the results of a 1-year monitoring of the inflammation markers' values for Interleukin-6 and Lipopolysaccharide binding protein (LBP)-types, both pre

  14. The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism.

    Science.gov (United States)

    von Loeffelholz, Christian; Lieske, Stefanie; Neuschäfer-Rube, Frank; Willmes, Diana M; Raschzok, Nathanael; Sauer, Igor M; König, Jörg; Fromm, Martin F; Horn, Paul; Chatzigeorgiou, Antonios; Pathe-Neuschäfer-Rube, Andrea; Jordan, Jens; Pfeiffer, Andreas F H; Mingrone, Geltrude; Bornstein, Stefan R; Stroehle, Peter; Harms, Christoph; Wunderlich, F Thomas; Helfand, Stephen L; Bernier, Michel; de Cabo, Rafael; Shulman, Gerald I; Chavakis, Triantafyllos; Püschel, Gerhard P; Birkenfeld, Andreas L

    2017-08-01

    Reduced expression of the Indy ("I am Not Dead, Yet") gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane-associated citrate transporter expressed highly in the liver, protects mice from high-fat diet-induced and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We studied a possible role of mIndy in human hepatic fat metabolism. In obese, insulin-resistant patients with nonalcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In nonhuman primates, a 2-year high-fat, high-sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription through the IL-6 receptor and activation of the transcription factor signal transducer and activator of transcription 3, and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-signal transducer and activator of transcription 3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx, and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and nonhuman primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 through mINDY. Targeting human mINDY may have therapeutic potential in obese patients with nonalcoholic fatty liver disease. German Clinical

  15. Interleukin-6 Deficiency Attenuates Retinal Ganglion Cell Axonopathy and Glaucoma-Related Vision Loss

    Directory of Open Access Journals (Sweden)

    Franklin D. Echevarria

    2017-05-01

    Full Text Available The pleotropic cytokine interleukin-6 (IL-6 is implicated in retinal ganglion cell (RGC survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis in vitro. However, it is unknown how IL-6 impacts glaucomatous degeneration in vivo. To study how IL-6 influences glaucomatous RGC axonopathy, accompanying glial reactivity, and resultant deficits in visual function, we performed neural tracing, histological, and neurobehavioral assessments in wildtype (B6;129SF2/J; WT and IL-6 knock-out mice (B6;129S2-IL6tm1kopf/J; IL-6-/- after 8 weeks of unilateral or bilateral microbead-induced glaucoma (microbead occlusion model. IOP increased by 20% following microbead injection in both genotypes (p < 0.05. However, deficits in wound healing at the site of corneal injection were noted. In WT mice, elevated IOP produced degenerating axon profiles and decreased axon density in the optic nerve by 15% (p < 0.01. In IL-6-/- mice, axon density in the optic nerve did not differ between microbead- and saline-injected mice (p > 0.05 and degenerating axon profiles were minimal. Preservation of RGC axons was reflected in visual function, where visual acuity decreased significantly in a time-dependent manner with microbead-induced IOP elevation in WT (p < 0.001, but not IL-6-/- mice (p > 0.05. Despite this preservation of RGC axons and visual acuity, both microbead-injected WT and IL-6-/- mice exhibited a 50% decrease in anterograde CTB transport to the superior colliculus, as compared to saline-injected controls (p < 0.01. Assessment of glial reactivity revealed no genotype- or IOP-dependent changes in retinal astrocytes. IOP elevation decreased microglia density and percent retinal area covered in WT mice (p < 0.05, while IL-6-/- mice exhibited only a decrease in density (p < 0.05. Together, our findings indicate that two defining features of RGC axonopathy—axon transport deficits and structural degeneration of

  16. Interleukin-6 dynamics as a basis for an early-warning monitor for sepsis and inflammation in individual pigs.

    Science.gov (United States)

    Tambuyzer, Tim; De Waele, Tine; Chiers, Koen; Berckmans, Daniel; Goddeeris, Bruno M; Aerts, Jean-Marie

    2014-06-01

    Static interleukin-6 (IL-6) levels of pigs contain considerable individual differences, which obstruct the practical use of IL-6 for disease monitoring purposes. It was hypothesised that interleukin-6 (IL-6) dynamics could be used to quantify these individual differences and carries critical information of the individual pig infection status. Time series of IL-6 responses in 25 pigs were analysed before and after infection by Actinobacillus pleuropneumoniae. The results indicated that amplitude increases of IL-6 fluctuations of individual pigs rather than static IL-6 values should be used as indicator of the infection state. This study shows the added value for IL-6 time series analyses of individual pigs. These results are a first step towards the development of objective individualised methods for monitoring and early detection of sepsis and inflammation processes in pigs by integrating animal response dynamics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Drugs elevating extracellular adenosine administered in vivo induce serum colony-stimulating activity and interleukin-6 in mice

    Czech Academy of Sciences Publication Activity Database

    Weiterová, Lenka; Hofer, Michal; Pospíšil, Milan; Znojil, V.; Štreitová, Denisa

    2007-01-01

    Roč. 56, č. 4 (2007), s. 463-473 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GP305/03/D050 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : extracellular adenosine * serum colony-stimulating activity * interleukin-6 Subject RIV: BO - Biophysics Impact factor: 1.505, year: 2007

  18. Neuroprotective effect of interleukin-6 regulation of voltage-gated Na+ channels of cortical neurons is time- and dose-dependent

    Directory of Open Access Journals (Sweden)

    Wei Xia

    2015-01-01

    Full Text Available Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours by studying voltage-gated Na + channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na + currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na + channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

  19. Maternal Systemic Interleukin-6 During Pregnancy Is Associated With Newborn Amygdala Phenotypes and Subsequent Behavior at 2 Years of Age.

    Science.gov (United States)

    Graham, Alice M; Rasmussen, Jerod M; Rudolph, Marc D; Heim, Christine M; Gilmore, John H; Styner, Martin; Potkin, Steven G; Entringer, Sonja; Wadhwa, Pathik D; Fair, Damien A; Buss, Claudia

    2018-01-15

    Maternal inflammation during pregnancy increases the risk for offspring psychiatric disorders and other adverse long-term health outcomes. The influence of inflammation on the developing fetal brain is hypothesized as one potential mechanism but has not been examined in humans. Participants were adult women (N = 86) who were recruited during early pregnancy and whose offspring were born after 34 weeks' gestation. A biological indicator of maternal inflammation (interleukin-6) that has been shown to influence fetal brain development in animal models was quantified serially in early, mid-, and late pregnancy. Structural and functional brain magnetic resonance imaging scans were acquired in neonates shortly after birth. Infants' amygdalae were individually segmented for measures of volume and as seeds for resting state functional connectivity. At 24 months of age, children completed a snack delay task to assess impulse control. Higher average maternal interleukin-6 concentration during pregnancy was prospectively associated with larger right amygdala volume and stronger bilateral amygdala connectivity to brain regions involved in sensory processing and integration (fusiform, somatosensory cortex, and thalamus), salience detection (anterior insula), and learning and memory (caudate and parahippocampal gyrus). Larger newborn right amygdala volume and stronger left amygdala connectivity were in turn associated with lower impulse control at 24 months of age, and mediated the association between higher maternal interleukin-6 concentrations and lower impulse control. These findings provide new evidence in humans linking maternal inflammation during pregnancy with newborn brain and emerging behavioral phenotypes relevant for psychiatric disorders. A better understanding of intrauterine conditions that influence offspring disease susceptibility is warranted to inform targeted early intervention and prevention efforts. Copyright © 2017 Society of Biological Psychiatry

  20. Variations of the interleukin-6 promoter are associated with features of the metabolic syndrome in Caucasian Danes

    DEFF Research Database (Denmark)

    Hamid, Y H; Rose, C S; Urhammer, S A

    2005-01-01

    The cytokine interleukin 6 (IL-6) is an essential regulator of the acute phase response associated with insulin-resistant states including type 2 diabetes and obesity. Three polymorphisms at positions -597, -572, and -174 of the IL6 promoter have been reported to influence IL6 transcription. The ....... The aim of this study was to investigate whether the IL6 promoter polymorphisms were associated with features of the WHO-defined metabolic syndrome and related quantitative traits in 7,553 Caucasian Danes....

  1. Function and molecular modeling of the interaction between human interleukin 6 and its HNK-1 oligosaccharide ligands.

    Science.gov (United States)

    Cebo, Christelle; Durier, Viviane; Lagant, Philippe; Maes, Emmanuel; Florea, Doina; Lefebvre, Tony; Strecker, Gérard; Vergoten, Gérard; Zanetta, Jean-Pierre

    2002-04-05

    Interleukin 6 (IL-6) is endowed with a lectin activity for oligosaccharide ligands possessing the HNK-1 epitope (3-sulfated glucuronic acid) found on some mammalian glycoprotein N-glycans (Cebo, C., Dambrouck, T., Maes, E., Laden, C., Strecker, G., Michalski, J. C., and Zanetta, J. P. (2001) J. Biol. Chem. 276, 5685-5691). Using high affinity oligosaccharide ligands, it is demonstrated that this lectin activity is responsible for the early dephosphorylation of tyrosine residues found on specific proteins induced by interleukin 6 in human resting lymphocytes. The gp130 glycoprotein, the signal-transducing molecule of the IL-6 pathway, is itself a molecule possessing the HNK-1 epitope. This indicates that IL-6 is a bi-functional molecule able to extracellularly associate its alpha-receptor with the gp130 surface complex. Computational modeling indicates that the lower energy conformers of the high affinity ligands of IL-6 have a common structure. Docking experiments of these conformers suggest that the carbohydrate recognition domain of IL-6 is localized in the domain previously identified as site 3 of IL-6 (Somers, W., Stahl, M., and Seehra, J. S. (1997) EMBO J. 16, 989-997), already known to be involved in interactions with gp130.

  2. BCG-induced interleukin-6 upregulation and BCG internalization in well and poorly differentiated human bladder cancer cell lines

    NARCIS (Netherlands)

    Bevers, R. F.; de Boer, E. C.; Kurth, K. H.; Schamhart, D. H.

    1998-01-01

    Intravesical bacillus Calmette-Guerin (BCG) is a successful therapy for superficial bladder cancer. However, the working mechanism of BCG after intravesical instillation is not completely understood. A functional role of urothelial (tumor) cells in the initiation of the BCG-induced immune reaction

  3. Ixodes ricinus Salivary Serpin IRS-2 Affects Th17 Differentiation via Inhibition of the Interleukin-6/STAT-3 Signaling Pathway

    Czech Academy of Sciences Publication Activity Database

    Páleníková, Jana; Lieskovská, Jaroslava; Langhansová, Helena; Kotsyfakis, Michalis; Chmelař, J.; Kopecký, Jan

    2015-01-01

    Roč. 83, č. 5 (2015), s. 1949-1956 ISSN 0019-9567 R&D Projects: GA ČR GAP302/12/2208 Institutional support: RVO:60077344 Keywords : T-cells * Borrelia burgdorferi * transcription factor Subject RIV: EC - Immunology Impact factor: 3.603, year: 2015

  4. Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer.

    Science.gov (United States)

    Brailo, Vlaho; Vucicevic-Boras, Vanja; Lukac, Josip; Biocina-Lukenda, Dolores; Zilic-Alajbeg, Iva; Milenovic, Aleksandar; Balija, Melita

    2012-01-01

    The aim of study was to compare salivary and serum concentrations of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with oral leukoplakia, oral cancer and healthy controls. Eighty eight patients (28 with oral cancer, 29 leukoplakia, and 31 healthy controls) were included in this study. Cytokine concentrations were measured by commercial enzyme linked immunoassay. Salivary IL-1β and IL-6 were significantly higher in oral cancer patients than in patients with leukoplakia and control group (pcancer patients. Patients with oral cancer have elevated levels of inflammatory cytokines in their saliva. Whether this elevation can be used for monitoring the malignant transformation of oral leukoplakia remains to be answered by further follow up studies.

  5. Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans.

    Science.gov (United States)

    Redwine, L; Hauger, R L; Gillin, J C; Irwin, M

    2000-10-01

    The objective of this study was to evaluate the effects of nocturnal sleep, partial night sleep deprivation, and sleep stages on circulating concentrations of interleukin-6 (IL-6) in relation to the secretory profiles of GH, cortisol, and melatonin. In 31 healthy male volunteers, blood samples were obtained every 30 min during 2 nights: uninterrupted, baseline sleep and partial sleep deprivation-early night (awake until 0300 h). Sleep was measured by electroencephalogram polysomnography. Sleep onset was associated with an increase in serum levels of IL-6 (P cortisol and melatonin showed no concordance with sleep. Loss of sleep may serve to decrease nocturnal IL-6 levels, with effects on the integrity of immune system functioning. Alternatively, given the association between sleep stages and IL-6 levels, depressed or aged populations who show increased amounts of REM sleep and a relative loss of slow wave sleep may have elevated nocturnal concentrations of IL-6 with implications for inflammatory disease risk.

  6. Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer

    Science.gov (United States)

    Vucicevic-Boras, Vanja; Lukac, Josip; Biocina-Lukenda, Dolores; Zilic-Alajbeg, Iva; Milenovic, Aleksandar; Balija, Melita

    2012-01-01

    Objectives: The aim of study was to compare salivary and serum concentrations of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with oral leukoplakia, oral cancer and healthy controls. Study design: Eighty eight patients (28 with oral cancer, 29 leukoplakia, and 31 healthy controls) were included in this study. Cytokine concentrations were measured by commercial enzyme linked immunoassay. Results: Salivary IL-1β and IL-6 were significantly higher in oral cancer patients than in patients with leukoplakia and control group (poral cancer patients. Conclusions: Patients with oral cancer have elevated levels of inflammatory cytokines in their saliva. Whether this elevation can be used for monitoring the malignant transformation of oral leukoplakia remains to be answered by further follow up studies. Key words: Cytokines, oral, leukoplakia, cancer. PMID:21743397

  7. [Changes in the interleukin-6 and interleukin-10 concentrations in the blood plasma of miners working in deep coal mines].

    Science.gov (United States)

    Plotkin, V Ia; Rebrov, B A; Belkina, E B

    2000-03-01

    Blood plasma levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured in 45 miners working in a deep coal mine immediately after work shift using an immunoenzyme technique. The highest IL-6 level was recorded in those miners engaged in hard work under most adverse conditions of underground workings--it was found to exceed the control values. The same group of workers demonstrated the lowest level of IL-10 that differed from the control value. Miners aged between 41 to 50 years working in a coal mine, their underground service duration 16 to 20 years, displayed a decline in the level of IL-6. The coal mine miners with the 11- to 15-year service duration revealed an increase in the level of IL-10.

  8. Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Fischer, Christian P; Hiscock, Natalie J; Penkowa, Milena

    2004-01-01

    Contracting human skeletal muscle is a major contributor to the exercise-induced increase of plasma interleukin-6 (IL-6). Although antioxidants have been shown to attenuate the exercise-induced increase of plasma IL-6, it is unknown whether antioxidants inhibit transcription, translation...... or translocation of IL-6 within contracting human skeletal muscle. Using a single-blind placebo-controlled design with randomization, young healthy men received an oral supplementation with either a combination of ascorbic acid (500 mg day(-1)) and RRR-alpha-tocopherol (400 i.u. day(-1)) (Treatment, n= 7...... in Control, but not in Treatment. In conclusion, our results show that supplementation with vitamins C and E attenuated the systemic IL-6 response to exercise primarily via inhibition of the IL-6 protein release from the contracting skeletal muscle per se....

  9. Generation of Human Immunosuppressive Myeloid Cell Populations in Human Interleukin-6 Transgenic NOG Mice

    Directory of Open Access Journals (Sweden)

    Asami Hanazawa

    2018-02-01

    Full Text Available The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs, and tumor-associated macrophages (TAMs that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg mouse strain, human interleukin (hIL-6-expressing NOG mice (NOG-hIL-6 transgenic mice. After transplantation of human hematopoietic stem cells (HSCs, the HSC-transplanted NOG-hIL-6 Tg mice (HSC-NOG-hIL-6 Tg mice showed enhanced human monocyte/macrophage differentiation. A significant number of human monocytes were negative for HLA-DR expression and resembled immature myeloid cells in the spleen and peripheral blood from HSC-NOG-hIL-6 Tg mice, but not from HSC-NOG non-Tg mice. Engraftment of HSC4 cells, a human head and neck squamous cell carcinoma-derived cell line producing various factors including IL-6, IL-1β, macrophage colony-stimulating factor (M-CSF, and vascular endothelial growth factor (VEGF, into HSC-NOG-hIL-6 Tg mice induced a significant number of TAM-like cells, but few were induced in HSC-NOG non-Tg mice. The tumor-infiltrating macrophages in HSC-NOG-hIL-6 Tg mice expressed a high level of CD163, a marker of immunoregulatory myeloid cells, and produced immunosuppressive molecules such as arginase-1 (Arg-1, IL-10, and VEGF. Such cells from HSC-NOG-hIL-6 Tg mice, but not HSC-NOG non-Tg mice, suppressed human T cell proliferation in response to antigen stimulation in in vitro cultures. These results suggest that functional human TAMs can be developed in NOG-hIL-6 Tg mice. This mouse model will contribute to the development of novel cancer immune therapies targeting immunoregulatory

  10. A common polymorphism near the interleukin-6 gene modifies the association between dietary fat intake and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Cuda C

    2012-01-01

    Full Text Available Cristina Cuda1, Bibiana Garcia-Bailo1,2, Mohamed Karmali1,2, Ahmed El-Sohemy1, Alaa Badawi21Department of Nutritional Sciences, University of Toronto, 2Office of Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, Ontario, CanadaBackground: Increasing evidence suggests a role for inflammation in the development of type 2 diabetes. Elevated levels of inflammatory cytokines, including interleukin-6, have been associated with insulin resistance, and dietary lipids can increase cytokine production. The objective of this study was to determine whether a single nucleotide polymorphism near the IL6 gene (rs7801406 modifies the relationship between dietary fat and markers of insulin sensitivity.Methods: Subjects were healthy men and women aged 20–29 years from the Toronto Nutrigenomics and Health Study. Dietary intake was estimated using a one-month semiquantitative food frequency questionnaire. Fasting blood samples were taken for genotyping and biomarker measurement.Results: The single nucleotide polymorphism was not associated with any of the measures of insulin sensitivity. However, it modified the relationship between total dietary fat and the homeostasis model assessment of insulin resistance (P = 0.053 for interaction. Total fat intake was positively related to HOMA-IR in individuals homozygous for the G allele (ß = 0.005 ± 0.002, P = 0.03, but not among heterozygotes. There was an inverse relationship between total fat intake and HOMA-IR in individuals who were homozygous for the A allele (β= –0.012 ± 0.006, P = 0.047.Conclusion: These findings suggest that dietary fat influences insulin sensitivity differently depending on genotype.Keywords: interleukin-6, insulin sensitivity, nutrigenomics, dietary fat

  11. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by interleukin 6 and interleukin 8 concentrations.

    Science.gov (United States)

    Mozrzymas, Renata; Duś-Żuchowska, Monika; Kałużny, Łukasz; Wenska-Chyży, Ewa; Walkowiak, Jarosław

    2016-01-01

    High oxidative stress and a reduced potential for free radical scavenging in phenylketonuria (PKU) patients, a phenomenon confirmed in a few studies, may lead to systemic chronic inflammation. The aim of this study was to compare the inflammation status, as assessed by interleukin 6 and interleukin 8 concentrations, in patients with PKU and in healthy controls. Twenty patients with classical PKU, aged 18-34 years and under dietary control, were enrolled in the study. The control group comprised of 20 healthy subjects matched for age and sex. Interleukin 6 and 8 levels were measured by enzyme-linked immunosorbent assay (ELISA) kits in all study participants. IL-6 concentrations in the study group ranged from 0.74 pg/ml to 1.34 pg/ml. No significant differences were found between IL-6 concentration between the study group and the control group (p = 0.989). IL-8 concentrations ranged from 17.56 pg/ml to 20.87 pg/ml. The obtained results of IL-8 levels did not differ significantly between the study group and control group (p = 0.192). No significant correlation was observed between Phe blood levels and IL-6 or IL-8 concentrations in the study group (ρ respectively: -0.225, 0.177). In a multivariate analysis, neither IL-6 nor IL-8 concentrations were correlated with sex, age, BMI and Phe levels. Phenylketonuria is not a risk factor for changes of inflammation status as assessed by IL-6 and IL-8 concentrations.

  12. Soluble membrane receptors, interleukin 6, procalcitonin and C reactive protein as prognostic markers in patients with severe sepsis and septic shock.

    Directory of Open Access Journals (Sweden)

    Juan-Jesús Ríos-Toro

    Full Text Available The objective of this study was to explore the diagnostic and prognostic value of soluble triggering receptor expressed on myeloid cell 1 (sTREM-1, soluble cluster of differentiation 14 (sCD14, soluble cluster of differentiation 163 (sCD163, interleukin-6 (IL-6, procalcitonin (PCT, and C-reactive protein (CRP serum levels for patients with severe sepsis and septic shock in an intensive care unit (ICU.Fifty patients admitted at the ICU with the diagnosis of severe sepsis or septic shock were studied. SOFA and APACHE II scores as well as serum biomarkers were measured at days 0, 2 and 5. The influence of these variables on 28-day mortality was analyzed. Twenty healthy individuals served as controls.Baseline serum concentrations of sTREM-1, sCD163, IL-6 and PCT correlated with SOFA score. Only sTREM-1 levels correlated with APACHE II score. The 28-day mortality rate for all patients was 42%. The absence of risk factors for infection, presence of septic shock, baseline values of sCD14 and decrease of PCT and IL-6 from baseline to day 5 were variables associated to mortality in the univariate analysis. The unique independent factor associated to mortality in the multivariate analysis was a decrease of PCT higher than 50% from days 0 to 5.Serum levels of sTREM-1 are correlated with the severity of sepsis. A 50% decrease of PCT was the unique variable associated with survival in the multivariate analysis.

  13. Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway

    International Nuclear Information System (INIS)

    Lamy, Sylvie; Akla, Naoufal; Ouanouki, Amira; Lord-Dufour, Simon; Béliveau, Richard

    2012-01-01

    Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention.

  14. Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lamy, Sylvie; Akla, Naoufal; Ouanouki, Amira; Lord-Dufour, Simon; Beliveau, Richard, E-mail: oncomol@nobel.si.uqam.ca

    2012-08-01

    Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6R{alpha}) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention.

  15. Serum levels of interleukin-6 and interleukin-8 as diagnostic markers of acute pyelonephritis in children

    Directory of Open Access Journals (Sweden)

    Abolfazl Mahyar

    2013-05-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Early diagnosis and treatment of acute pyelonephritis in children is of special importance in order to prevent serious complications. This study was conducted to determine the diagnostic value of serum interleukin (IL-6 and IL-8 in children with acute pyelonephritis. &lt;b&gt;Methods:&lt;/b&gt; Eighty seven patients between 1 month to 12 years old with urinary tract infection (UTI were divided into 2 groups based on the result of 99m-technetium dimercapto-succinic acid (DMSA renal scan: acute pyelonephritis (n=37 and lower UTI (n=50 groups. White blood cell (WBC count, neutrophil (Neutl count, erythrocyte sedimentation rate (ESR, C-reactive protein (CRP concentration, platelet count, and serum IL-6 and IL-8 concentrations of both groups were measured and compared . &lt;b&gt;Results:&lt;/b&gt; There was a significant difference between two groups regarding WBC count, Neutl count, ESR, and CRP concentration (P&lt;0.05. In addition, the difference between the two groups regarding serum IL-6 and IL-8 concentrations was not significant (IL-6, 60 and 35.4 pg/mL and IL-8, 404 and 617 pg/mL, respectively. The sensitivity and specificity of serum IL-6 and IL-8 for diagnosis of acute pyelonephritis were 73%, 42% and 78%, 32%, respectively. Sensitivity, specificity, negative and positive predictive values of serum IL-6 and IL-8 were less than those of acute phase serum reactants such as CRP. &lt;b&gt;Conclusion:&lt;/b&gt; This study showed that there was no significant difference between acute pyelonephritis and lower UTI groups regarding serum IL-6 and IL-8 levels. Therefore, despite confirming results of previous studies, it seems that IL-6 and IL-8 are not suitable markers for differentiating between acute pyelonephritis and lower UTI.

  16. [Influence of zinc administered by total parenteral nutrition on plasmatic zinc levels, on reactive C protein, on serum interleukin-6 and on serum interleukin-6 soluble receptor, in critical patients].

    Science.gov (United States)

    Menéndez, A M; De Portela, M L; Weisstaub, A; Montemerlo, H; Guidoni, M E; Rusí, F; Zeni, S

    2009-01-01

    To study the interrelationship between serum Interleukin-6 (IL-6), serum Interleukin-6 soluble Receptor (IL-6 sR), C-Reactive Protein (C-RP), plasmatic Zinc levels (PlZn) and their response in relation to Zn administered by TPN, in critical patients. 17 patients, receiving TPN as a consequence of acute pancreatitis (n = 4) or after a major abdominal surgery due to intestinal cancer (n = 7), intestinal fístula (n = 3), intestinal obstruction (n = 2) or intestinal íleus (n = 1) were studied. At the beginning (To) and at the end of the TPN administration (6-21 days) serum IL-6 and IL-6 sR were determined by ELISA; C-RP ultrasensitive (C-RP us) by inmunoturbidimetric method; Zn was determined in TPN and in plasma by Atomic Absorption Spectrometry. Characteristics of the patients were (mean +/- SD and ranges): age: 60.6 +/- 11.7 (37-77) years; BMI (kg/m(2)): 26.0 +/- 3.4 (19.9-34.0). The results (mean +/- standard deviation and ranges) were: Zn provided by TPN (mg/d): 6.1 +/- 2.0 (range 2.8 to 10.8). Biochemical levels were, at To and Tf, respectively: (mean+/-SD and ranges) were at To y Tf, respectively: Zn Pl (microg/dl): 104 +/- 46 (35-177); 120 +/- 55 (52-229); IL-6 (pg/mL) 93 +/- 74 (10-262); 117 +/- 180 (7-761); IL6sR (pg/mL): 1,012 +/- 322 (589-1855); 1,269 +/- 451 (631-2195); C-RP us (mg/L): 71 +/- 63 (2-196); 65 +/- 43 (0-137). There was no correlation between variations of IL6, IL6sR, C-RP, PlZn levels and the daily amount of Zn administered in the TPN mixtures. Two patients presented a bad evolution; they received 4.2 and 5.2 md/d of Zn and showed an increase of IL6 levels, maintained high levels of IL6sR but C-RP levels decreased. the range of 2.8 to 10.8 mg/d of Zn administered in TPN mixtures did not exacerbate the inflammatory response.

  17. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis.

    Science.gov (United States)

    Swerdlow, Daniel I; Holmes, Michael V; Kuchenbaecker, Karoline B; Engmann, Jorgen E L; Shah, Tina; Sofat, Reecha; Guo, Yiran; Chung, Christina; Peasey, Anne; Pfister, Roman; Mooijaart, Simon P; Ireland, Helen A; Leusink, Maarten; Langenberg, Claudia; Li, Ka Wah; Palmen, Jutta; Howard, Philip; Cooper, Jackie A; Drenos, Fotios; Hardy, John; Nalls, Michael A; Li, Yun Rose; Lowe, Gordon; Stewart, Marlene; Bielinski, Suzette J; Peto, Julian; Timpson, Nicholas J; Gallacher, John; Dunlop, Malcolm; Houlston, Richard; Tomlinson, Ian; Tzoulaki, Ioanna; Luan, Jian'an; Boer, Jolanda M A; Forouhi, Nita G; Onland-Moret, N Charlotte; van der Schouw, Yvonne T; Schnabel, Renate B; Hubacek, Jaroslav A; Kubinova, Ruzena; Baceviciene, Migle; Tamosiunas, Abdonas; Pajak, Andrzej; Topor-Madry, Roman; Malyutina, Sofia; Baldassarre, Damiano; Sennblad, Bengt; Tremoli, Elena; de Faire, Ulf; Ferrucci, Luigi; Bandenelli, Stefania; Tanaka, Toshiko; Meschia, James F; Singleton, Andrew; Navis, Gerjan; Mateo Leach, Irene; Bakker, Stephan J L; Gansevoort, Ron T; Ford, Ian; Epstein, Stephen E; Burnett, Mary Susan; Devaney, Joe M; Jukema, J Wouter; Westendorp, Rudi G J; Jan de Borst, Gert; van der Graaf, Yolanda; de Jong, Pim A; Mailand-van der Zee, Anke-Hilse; Klungel, Olaf H; de Boer, Anthonius; Doevendans, Pieter A; Stephens, Jeffrey W; Eaton, Charles B; Robinson, Jennifer G; Manson, JoAnn E; Fowkes, F Gerry; Frayling, Timonthy M; Price, Jackie F; Whincup, Peter H; Morris, Richard W; Lawlor, Debbie A; Smith, George Davey; Ben-Shlomo, Yoav; Redline, Susan; Lange, Leslie A; Kumari, Meena; Wareham, Nick J; Verschuren, W M Monique; Benjamin, Emelia J; Whittaker, John C; Hamsten, Anders; Dudbridge, Frank; Delaney, J A Chris; Wong, Andrew; Kuh, Diana; Hardy, Rebecca; Castillo, Berta Almoguera; Connolly, John J; van der Harst, Pim; Brunner, Eric J; Marmot, Michael G; Wassel, Christina L; Humphries, Steve E; Talmud, Philippa J; Kivimaki, Mika; Asselbergs, Folkert W; Voevoda, Mikhail; Bobak, Martin; Pikhart, Hynek; Wilson, James G; Hakonarson, Hakon; Reiner, Alex P; Keating, Brendan J; Sattar, Naveed; Hingorani, Aroon D; Casas, Juan Pablo

    2012-03-31

    A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown. Applying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis. In 40 studies including up to 133,449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9·45%, 95% CI 8·34-10·57) as well as reduced C-reactive protein (decrease per allele 8·35%, 95% CI 7·31-9·38) and fibrinogen concentrations (decrease per allele 0·85%, 95% CI 0·60-1·10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4-8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25,458 coronary heart disease cases and 100,740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0·95, 95% CI 0·93-0·97, p=1·53×10(-5)). On the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing

  18. Promotion of Endoplasmic Reticulum-Associated Degradation of Procathepsin D by Human Herpesvirus 8-Encoded Viral Interleukin-6.

    Science.gov (United States)

    Chen, Daming; Nicholas, John

    2015-08-01

    The interleukin-6 homologue (viral interleukin-6 [vIL-6]) of human herpesvirus 8 is implicated in viral pathogenesis due to its proproliferative, inflammatory, and angiogenic properties, effected through gp130 receptor signaling. In primary effusion lymphoma (PEL) cells, vIL-6 is expressed latently and is essential for normal cell growth and viability. This is mediated partly via suppression of proapoptotic cathepsin D (CatD) via cocomplexing of the endoplasmic reticulum (ER)-localized CatD precursor, pro-CatD (pCatD), and vIL-6 with the previously uncharacterized ER membrane protein vitamin K epoxide reductase complex subunit 1 variant 2 (VKORC1v2). vIL-6 suppression of CatD occurs also during reactivated productive replication in PEL cells and is likely to contribute to proreplication functions of vIL-6. Here, we report that vIL-6 suppresses CatD through vIL-6, VKORC1v2, and pCatD association with components of the ER-associated degradation (ERAD) machinery. In transfected cells, expression of vIL-6 along with CatD led to proteasome-dependent (inhibitor-sensitive) decreases in CatD levels and the promotion of pCatD polyubiquitination. Depletion of particular ERAD-associated isomerases, lectins, and translocon components, including ERAD E3 ubiquitin ligase HRD1, diminished suppression of CatD by vIL-6. Coprecipitation assays identified direct or indirect interactions of VKORC1v2, vIL-6, and pCatD with translocon proteins (SEL1L and/or HRD1) and ERAD-associated lectins OS9 and XTP3-B. Endogenous CatD expression in PEL cells was increased by depletion of ERAD components, and suppression of CatD by vIL-6 overexpression in PEL cells was dependent on HRD1. Our data reveal a new mechanism of ER-localized vIL-6 activity and further characterize VKORC1v2 function. Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6), unlike cellular IL-6 proteins, is secreted inefficiently and sequestered mainly in the endoplasmic reticulum (ER), from where it can signal through the gp

  19. Prognostic and clinicopathological significance of serum interleukin-6 expression in colorectal cancer: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang Z

    2015-12-01

    Full Text Available Zhen Wang,1 Pin Wu,1,2 Dang Wu,1 Zhigang Zhang,3 Guoming Hu,1 Shuai Zhao,1 Yucheng Lai,1 Jian Huang1,41Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Key Laboratory of Molecular Biology in Medical Sciences, China National Ministry of Education, 2Department of Thoracic Surgery, 3Department of Gynecology, 4Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of ChinaPurpose: Interleukin-6 (IL-6 plays an important role in human colorectal cancer (CRC development. However, the exact clinical and prognostic significance of IL-6 in CRC is still unclear. Here, we conducted this meta-analysis to explore this issue in detail.Methods: A meta-analysis was performed to clarify the association between serum IL-6 expression and clinical outcomes in articles published up to June 2015. Weighted mean difference (WMD and its corresponding 95% confidence interval (CI were used to assess the association between serum IL-6 expression and the clinicopathological characteristics of CRC. Hazard ratio (HR with 95% CI was used to quantify the predictive value of IL-6 on CRC prognosis.Results: Fourteen studies comprising 1,245 patients were included. Analysis of these data showed that serum IL-6 expression was highly correlated with poor 5-year overall survival (OS rate (HR =0.43, 95% CI: 0.31–0.59, P=0.755. Simultaneously, we also found that serum IL-6 expression was associated with certain clinical parameters of CRC, such as tumor invasion (T category: T0–T2, T3–T4 (WMD =3.15, 95% CI: 1.92–4.39, P=0.816, distant metastasis (M category: M0, M1 (WMD =4.69, 95% CI: 3.33–6.06, P=0.377, and tumor stage (I–II, III–IV (WMD =2.65, 95% CI: 1.09–4.21, P=0.066.Conclusion: A high serum IL-6 expression is associated with adverse OS in CRC. The IL-6 expression can be an important supplement in establishing prognostic score

  20. The role of interleukin-6 in pulmonary and systemic manifestations in a murine model of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pauwels, Nele S; Bracke, Ken R; Maes, Tania; Pilette, Charles; Joos, Guy F; Brusselle, Guy G

    2010-10-01

    Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and extrapulmonary manifestations including systemic inflammation and weight loss. Increased levels of interleukin-6 (IL-6) have been demonstrated in sputum and serum of COPD patients. Therefore, the authors investigated the in vivo role of IL-6 in a murine model of COPD. Wild-type (WT) and IL-6 knockout (KO) mice were exposed subacutely (4 weeks) and chronically (24 weeks) to air or cigarette smoke (CS). Subacute and chronic CS exposure significantly increased pulmonary IL-6 mRNA expression in lung tissue and IL-6 protein levels in bronchoalveolar lavage fluid of WT mice. However, CS-induced accumulation of inflammatory cells at both time points and lymphoid aggregate formation upon chronic CS exposure were independent of IL-6. Chonic CS exposure was associated with a significant failure to gain weight in both WT mice and IL-6 KO mice. Remarkably, air-exposed IL-6 KO mice have lower body weight, serum leptin levels, and adipose tissue mass compared to air-exposed WT mice. In conclusion, IL-6 is of minor importance in CS-induced pulmonary and systemic manifestations in mice, but this study confirms the role for IL-6 as regulator of body weight and body composition.

  1. Antagonistic effect of disulfide-rich peptide aptamers selected by cDNA display on interleukin-6-dependent cell proliferation

    International Nuclear Information System (INIS)

    Nemoto, Naoto; Tsutsui, Chihiro; Yamaguchi, Junichi; Ueno, Shingo; Machida, Masayuki; Kobayashi, Toshikatsu; Sakai, Takafumi

    2012-01-01

    Highlights: ► Disulfide-rich peptide aptamer inhibits IL-6-dependent cell proliferation. ► Disulfide bond of peptide aptamer is essential for its affinity to IL-6R. ► Inhibitory effect of peptide depends on number and pattern of its disulfide bonds. -- Abstract: Several engineered protein scaffolds have been developed recently to circumvent particular disadvantages of antibodies such as their large size and complex composition, low stability, and high production costs. We previously identified peptide aptamers containing one or two disulfide-bonds as an alternative ligand to the interleukin-6 receptor (IL-6R). Peptide aptamers (32 amino acids in length) were screened from a random peptide library by in vitro peptide selection using the evolutionary molecular engineering method “cDNA display”. In this report, the antagonistic activity of the peptide aptamers were examined by an in vitro competition enzyme-linked immunosorbent assay (ELISA) and an IL-6-dependent cell proliferation assay. The results revealed that a disulfide-rich peptide aptamer inhibited IL-6-dependent cell proliferation with similar efficacy to an anti-IL-6R monoclonal antibody.

  2. Effect of nutritional status and dietary patterns on human serum C-reactive protein and interleukin-6 concentrations.

    Science.gov (United States)

    Smidowicz, Angelika; Regula, Julita

    2015-11-01

    The inflammatory process plays an important role in the pathogenesis of many chronic diseases, such as cardiovascular diseases, diabetes mellitus type 2, and metabolic syndrome. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) are widely tested inflammatory markers involved in the development of these diseases. Several studies indicate a relation between nutritional status and the concentrations of human high-sensitivity CRP and IL-6. Similarly, the role of diet in reducing inflammation and thereby modulating the risk of non-communicable diseases is supported by numerous studies. This review focuses on the effects of the selected nutrition models in humans on the concentrations of CRP and IL-6. It seems that the Mediterranean diet model is most effective in inhibiting inflammation. The Dietary Approaches to Stop Hypertension model and the plant nutrition model also have proven to be beneficial. The data on low-fat and low-carbohydrate diets are inconclusive. Comprehensive studies are necessary, taking into account the cumulative effect of dietary and other factors on the inflammatory process. © 2015 American Society for Nutrition.

  3. Effect of eccentric exercise with reduced muscle glycogen on plasma interleukin-6 and neuromuscular responses of musculus quadriceps femoris.

    Science.gov (United States)

    Gavin, James P; Myers, Stephen D; Willems, Mark E T

    2016-07-01

    Eccentric exercise can result in muscle damage and interleukin-6 (IL-6) secretion. Glycogen availability is a potent stimulator of IL-6 secretion. We examined effects of eccentric exercise in a low-glycogen state on neuromuscular function and plasma IL-6 secretion. Twelve active men (23 ± 4 yr, 179 ± 5 cm, 77 ± 10 kg, means ± SD) completed two downhill treadmill runs (gradient, -12%, 5 × 8 min; speed, 12.1 ± 1.1 km/h) with normal (NG) and reduced muscle glycogen (RG) in randomized order and at least 6 wk apart. Muscle glycogen was reduced using an established cycling protocol until exhaustion and dietary manipulation the evening before the morning run. Physiological responses were measured up to 48 h after the downhill runs. During recovery, force deficits of musculus quadriceps femoris by maximal isometric contractions were similar. Changes in low-frequency fatigue were larger with RG. Voluntary activation and plasma IL-6 levels were similar in recovery between conditions. It is concluded that unaccustomed, damaging eccentric exercise with low muscle glycogen of the m. quadriceps femoris 1) exacerbated low-frequency fatigue but 2) had no additional effect on IL-6 secretion. Neuromuscular impairment after eccentric exercise with low muscle glycogen appears to have a greater peripheral component in early recovery. Copyright © 2016 the American Physiological Society.

  4. Serum brain-derived neurotrophic factor and interleukin-6 response to high-volume mechanically demanding exercise.

    Science.gov (United States)

    Verbickas, Vaidas; Kamandulis, Sigitas; Snieckus, Audrius; Venckunas, Tomas; Baranauskiene, Neringa; Brazaitis, Marius; Satkunskiene, Danguole; Unikauskas, Alvydas; Skurvydas, Albertas

    2018-01-01

    The aim of this study was to follow circulating brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) levels in response to severe muscle-damaging exercise. Young healthy men (N = 10) performed a bout of mechanically demanding stretch-shortening cycle exercise consisting of 200 drop jumps. Voluntary and electrically induced knee extension torque, serum BDNF levels, and IL-6 levels were measured before and for up to 7 days after exercise. Muscle force decreased by up to 40% and did not recover by 24 hours after exercise. Serum BDNF was decreased 1 hour and 24 hours after exercise, whereas IL-6 increased immediately and 1 hour after but recovered to baseline by 24 hours after exercise. IL-6 and 100-Hz stimulation torque were correlated (r = -0.64, P exercise. In response to acute, severe muscle-damaging exercise, serum BDNF levels decrease, whereas IL-6 levels increase and are associated with peripheral fatigue. Muscle Nerve 57: E46-E51, 2018. © 2017 Wiley Periodicals, Inc.

  5. Exercise-induced liver chemokine CXCL-1 expression is linked to muscle-derived interleukin-6 expression

    DEFF Research Database (Denmark)

    Pedersen, Line; Pilegaard, Henriette; Hansen, Jakob

    2011-01-01

    . The aim of this study was to unravel the mechanisms whereby CXCL-1 is regulated by exercise inmice. After a single bout of exercise, CXCL-1 protein increased in serum(2.4-fold), and CXCL-1 mRNA in muscle (6.5-fold) and liver (41-fold). These increases in CXCL-1 were preceded by increases in serum...... interleukin-6 (IL-6) and muscle IL-6 mRNA. In contrast, exercise-induced regulation of liver CXCL-1 mRNA expression was completely blunted in IL-6 knockout mice. Based on these findings, we examined the possible existence of a muscle-to-liver axis by overexpressing IL-6 in muscles. This resulted in increases...... significantly augmented serum CXCL-1, and CXCL-1 expression in liver and muscle. Taken together, these data indicate that liver is the main source of serum CXCL-1 during exercise in mice, and that the CXCL-1 expression in the liver is regulated by muscle-derived IL-6....

  6. The Role of Serum Level of Interleukin-6 in Severity of Pulmonary Complications of Sulfur Mustard Injuries

    Directory of Open Access Journals (Sweden)

    Majid Shohrati

    2015-07-01

    Full Text Available Diverse studies suggest that interleukin-6 (IL6, as a member of cytokines family, has a major role in inflammatory processes of airways and lungs. In this study, an attempt was made to determine the serum level of IL6 in sulfur mustard (SM injured patients and its comparison with controls. The measured IL6 mean level in patients with chemical injuries (0.76±0.3 ng/ml was significantly higher than the control group’s mean level (0.34±0.12 ng/ml. Furthermore, patients with moderate to severe symptoms had a serum level of (0.95±0.92 ng/ml which was significantly higher than mild (0.47±0.54 and control (0.34±0.12 groups. The outcome of this research program demonstrates that an increase in serum level of IL6 can have a role in pulmonary complications of SM, similar to other well defined pulmonary diseases. However, further studies are required to clarify the role and mechanism of IL6 in such patients.

  7. Association of Plasma Heat Shock Protein 70, Interleukin 6, and Creatine Kinase Concentrations in a Healthy, Young Adult Population

    Directory of Open Access Journals (Sweden)

    Carmen Contreras-Sesvold

    2015-01-01

    Full Text Available Variations of baseline plasma concentrations of creatine kinase (CK, heat shock protein 70 (HSP70, and interleukin 6 (IL-6 have been reported. We report categorical associations which may influence these protein levels. Methods. Blood was harvested for DNA and plasma protein analysis from 567 adults. Mean protein levels of CK, HSP70, and IL-6 were compared by sex, ethnicity, genetic variants—CKMM Nco1 (rs1803285, HSPA1B +A1538G (rs1061581, and IL6 G-174C (rs1800795—self-reported history of exercise, oral contraceptive use, and dietary supplement use. Results. SNP major allele frequencies for CKMM, HSPA1B, and IL6 were 70% A, 57% A, and 60%. Mean CK statistically differed by sex, ethnicity, oral contraceptives, and caffeine. Plasma HSP70 differed by caffeine and protein. Mean IL-6 concentration differed by sex, ethnicity, and genotype. Plasma IL-6 was significantly lower (29% in males (1.92 ± 0.08 pg/mL and higher (29% among African Americans (2.85 ± 0.50 pg/mL relative to the others. IL6 G-174C GG genotype (2.23 ± 0.14 pg/mL was 19% greater than CG or CC genotypes. Conclusion. Differences in baseline CK and IL-6 plasma protein concentrations are associated with genetics, sex, ethnicity, and the use of oral contraceptives, caffeine, and protein supplements in this young and athletic population.

  8. Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Mitrugno Valentina

    2010-11-01

    Full Text Available Abstract Background Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6, a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells. Results Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions. Conclusion We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.

  9. Interleukin-6, intracellular adhesion molecule-1, and glycodelin A levels in serum and peritoneal fluid as biomarkers for endometriosis.

    Science.gov (United States)

    Mosbah, Alaa; Nabiel, Yasmin; Khashaba, Eman

    2016-09-01

    To compare levels of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1), and glycodelin A in serum and peritoneal fluid of patients with and without endometriosis, and to correlate levels with disease stage. An observational study was undertaken at Mansoura University Hospital, Egypt, between March 2014 and June 2015. Patients aged 21-48 years laparoscopically diagnosed with endometriosis and those without endometriosis who underwent laparoscopy for tubal ligation were included. Levels of IL-6, ICAM-1, and glycodelin A were measured in samples of serum and peritoneal fluid. Receiver operating characteristic curves were used to evaluate diagnostic accuracy. Forty-eight women with endometriosis and 20 without the disorder were included. IL-6 and glycodelin A levels in serum and peritoneal fluid were higher in the endometriosis group than in the control group (Pperitoneal fluid markers were 85.4% and 89.0%, 60.4% and 50.0%, and 89.6% and 90.0%, respectively. IL-6 and glycodelin A levels in serum and peritoneal fluid increased with disease stage (Pendometriosis and are positively correlated with the disease stage. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6

    DEFF Research Database (Denmark)

    Molinero, Amalia; Penkowa, Milena; Hernández, Joaquín

    2003-01-01

    Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP-IL6 mice) causes significant damage and alters the expression of many genes, including a dramatic upregulation of metallothionein-I (MT-I). The findings...... in this report support the idea that the upregulation of MT-I observed in GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, GFAP-IL6 mice that were crossed with TgMTI transgenic mice (GFAP-IL6xTgMTI) and overexpressed MT-I in the brain showed a decreased upregulation of cytokines...... such as IL-6 and a diminished recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. The GFAP-IL6 mice showed clear evidence of increased oxidative stress, which was significantly decreased by MT-I overexpression. Interestingly, MT-I overexpression increased...

  11. The study of vitamin D administration effect on CRP and Interleukin-6 as prognostic biomarkers of ventilator associated pneumonia.

    Science.gov (United States)

    Miroliaee, Amir Ebrahim; Salamzadeh, Jamshid; Shokouhi, Shervin; Sahraei, Zahra

    2018-04-01

    In regard with the effect of immune-stimulants in the treatment of infectious diseases, the effect of vitamin D administration on the outcome of patients with Ventilator-Associated Pneumonia (VAP) with a high rate of mortality, was studied. In this trial, 46 adult patients suffering from VAP and vitamin D deficiency were enrolled. The first group of patients received single intramuscular injection of vitamin D (300000Unit), while the other group were given the placebo. Administration of vitamin D significantly enhanced its levels (P<0.0001) in the treated patients (12.28±8.26) in comparison with placebo group (1.15±1.50). Serum Interleukin-6 levels were significantly reduced in the treated group compared to placebo (P=0.01). Although C-Reactive protein (CRP) levels showed an improving trend in the vitamin D group, no significant difference between groups (P=0.12) was found. Interestingly, the mortality rate of patients that treated with vitamin D (5/24) was significantly lower (p=0.04) than that of the placebo group (11/22). Our results indicate that vitamin D administration can significantly reduce the IL-6 as prognostic marker in VAP patients, and must be considered as adjunct option in the treatment of VAP patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Circulating microparticles in patients with coronary heart disease and its correlation with interleukin-6 and C-reactive protein.

    Science.gov (United States)

    Cui, Ying; Zheng, Lihui; Jiang, Ming; Jia, Ru; Zhang, Xiao; Quan, Qishan; Du, Guiqin; Shen, Dongjin; Zhao, Xiaodan; Sun, Wenying; Xu, Hongwei; Huang, Lijuan

    2013-11-01

    Microparticles (MPs) are vesicles released from activated or apoptotic cells. MP derive from various cells, most notably platelets, but also leucocytes, lymphocytes, erythrocytes, and endothelial cells. The aim of this study was to investigate endothelial MP (EMP), platelet MP (PMP), lymphocyte MP and monocyte MP and TF-positive MPs (TF+ MPs) in patients with coronary heart disease (CHD), and to evaluate the correlation of these MPs with Interleukin-6 (IL-6) and C-reactive protein (CRP). Different cell-derived MPs and TF+ MPs were analyzed by flow cytometry in 40 patients with myocardial infarction (MI), 30 unstable angina (UA), 20 stable angina (SA) and 20 healthy individuals, and IL-6 and CRP were determined by ELISA and special protein analyzer, respectively. Compared with SA and control, EMP and PMP was significantly elevated in MI and UA (P < 0.001), and TF+ MPs was significantly elevated in MI and UA (P < 0.001). EMP and PMP correlated with IL-6 (r = 0.822, P < 0.001 and r = 0.567, P < 0.001; respectively) or CRP level (r = 0.597, P < 0.001 and r = 0.66, P < 0.001; respectively). Different cell-derived MPs in CHD may indicate the different pathophysiological changes in vessels, and MPs may both participate in the development of thrombosis and enhance the vascular inflammation.

  13. Maternal serum interleukin-6 levels predict impending funisitis in preterm premature rupture of membranes after completion of antibiotics.

    Science.gov (United States)

    Canzoneri, Bernard J; Grotegut, Chad A; Swamy, Geeta K; Brancazio, Leo R; Sinclair, Tammy; Heine, Phillips R; Murtha, Amy P

    2012-08-01

    To determine if maternal serum interleukin-6 (IL-6) levels remain predictive of funisitis after completion of antibiotic administration in preterm premature rupture of membranes (PPROM). A secondary analysis of a prospective cohort study. Daily blood samples obtained from PPROM subjects were analyzed for IL-6 by enzyme-linked immunosorbent assay. Subjects (N = 39) delivered >7 days post admission and were divided into those with and without funisitis. Data were analyzed using Mann-Whitney U test. Maternal serum IL-6 levels obtained 24-48 hours and 48-72 hours before delivery are elevated in PPROM subjects with funisitis compared to those without funisitis (6.3 vs. 2.7 pg/ml, P Receiver operator characteristic curve revealed an IL-6 level of 1.98 pg/ml had sensitivity of 86.7%, specificity of 46.7%, positive predictive value of 61.9% and negative predictive value of 77.8%. This data suggests that maternal serum IL-6 levels continue to be predictive of PPROM subjects destined to develop funisitis after completion of antibiotics.

  14. Bee Venom Acupuncture Reduces Interleukin-6, Increases Interleukin-10, and Induces Locomotor Recovery in a Model of Spinal Cord Compression.

    Science.gov (United States)

    Nascimento de Souza, Raquel; Silva, Fernanda Kohn; Alves de Medeiros, Magda

    2017-06-01

    Spinal cord injuries (SCIs) initiate a series of molecular and cellular events in which inflammatory responses can lead to major neurological dysfunctions. The present study aims to investigate whether bee venom (BV) acupuncture applied at acupoints ST36 (Zusanli) and GV3 (Yaoyangquan) could minimize locomotor deficits and the magnitude of neural tissue losses, and change the balance between pro- and anti-inflammatory cytokines after an SCI by compression. Wistar rats were subjected to an SCI model by compression in which a 2-French Fogarty embolectomy catheter was inflated in the extradural space. The effects of BV acupuncture, in which 20 μL of BV diluted in saline (0.08 mg/kg) was injected at acupoints GV3 and ST36 [BV(ST36+GV3)-SCI] was compared with BV injected at nonacupoints [BV(NP)-SCI] and with no treatment [group subjected only to SCI (CTL-SCI)]. The BV(ST36+GV3)-SCI group showed a significant improvement in the locomotor performance and a decrease of lesion size compared with the controls. BV acupuncture at the ST36 + GV3 increased the expression of interleukin-10 (anti-inflammatory) at 6 hours and reduced the expression of interleukin-6 (proinflammatory) at 24 hours after SCI compared with the controls. Our results suggest that BV acupuncture can reduce neuroinflammation and induce recovery in the SCI compression model. Copyright © 2017. Published by Elsevier B.V.

  15. Interleukin-6 triggers human cerebral endothelial cells proliferation and migration: The role for KDR and MMP-9

    International Nuclear Information System (INIS)

    Yao, Jianhua S.; Zhai Wenwu; Young, William L.; Yang Guoyuan

    2006-01-01

    Interleukin-6 (IL-6) is involved in angiogenesis. However, the underlying mechanisms are unknown. Using human cerebral endothelial cell (HCEC), we report for First time that IL-6 triggers HCEC proliferation and migration in a dose-dependent manner, specifically associated with enhancement of VEGF expression, up-regulated and phosphorylated VEGF receptor-2 (KDR), and stimulated MMP-9 secretion. We investigated the signal pathway of IL-6/IL-6R responsible for KDR's regulation. Pharmacological inhibitor of PI3K failed to inhibit IL-6-mediated VEGF overexpression, while blocking ERK1/2 with PD98059 could abolish IL-6-induced KDR overexpression. Further, neutralizing endogenous VEGF attenuated KDR expression and phosphorylation, suggesting that IL-6-induced KDR activation is independent of VEGF stimulation. MMP-9 inhibitor GM6001 significantly decreases HCEC proliferation and migration (p < 0.05), indicating the crucial function of MMP-9 in promoting angiogenic changes in HCECs. We conclude that IL-6 triggers VEGF-induced angiogenic activity through increasing VEGF release, up-regulates KDR expression and phosphorylation through activating ERK1/2 signaling, and stimulates MMP-9 overexpression

  16. Soluble urokinase-type plasminogen activator receptor (suPAR) and interleukin-6 levels in hyperemesis gravidarum.

    Science.gov (United States)

    Desdicioglu, Raziye; Yildirim, Melahat; Kocaoglu, Gulcan; Demir Cendek, Busra; Avcioglu, Gamze; Tas, Emre Erdem; Sengul, Ozlem; Erel, Ozcan; Yavuz, Ayse Filiz

    2017-10-09

    The aim was to compare serum soluble urokinase-type plasminogen activator receptor (suPAR) levels as well as interleukin-6 levels (IL-6) in pregnant women with hyperemesis gravidarum (HG) and asymptomatic pregnant women. Our study population consists of voluntary first trimester-pregnant women who applied to the outpatient clinic of the department of obstetrics and gynecology of Ankara Ataturk Training and Research Hospital. Between February and May 2016, 60 pregnant women were included in our prospective study. Serum suPAR and IL-6 levels were evaluated with the ELISA method. Twenty-nine pregnant women with HG and 31 asymptomatic pregnant women were included in the study. Serum suPAR level in the HG group was measured as 0.36 ± 0.56 ng/ml, whereas this level in the healthy pregnant control group was measured as 0.15 ± 0.15 ng/ml (p hyperemesis gravidarum. Copyright © 2017. Published by Elsevier Taiwan LLC.

  17. Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and Regulated by Interleukin-6 Deficiency in Mouse Placenta

    Directory of Open Access Journals (Sweden)

    Patricia Pazos

    2014-01-01

    Full Text Available The placenta produces a number of signaling molecules including metabolic and reproductive hormones as well as several inflammatory mediators. Among them, Interleukin-6 (IL-6, a well-known immune and metabolic regulator, acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. IL-6 interacts with key hypothalamic neuropeptidergic systems controlling energy homeostasis such as those producing the orexigenic/anabolic: neuropeptide Y (NPY and agouti-related peptide (AgRP and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC and cocaine and amphetamine regulated transcript (CART. Human and rat placenta have been identified as source of these neuropeptides, but their expression and regulation in murine placental tissues remain unknown. Therefore, placental mRNA levels of IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days 13, 15, and 18 were analyzed by real time PCR, as were the effect of IL-6 deficiency (IL-6 knockout mice on their placental expression. Our results showed that placenta-derived neuropeptides were regulated by gestational age and IL-6 throughout the second half of mouse pregnancy. These data suggest that IL-6 may participate in the fine tune control of energy balance during pregnancy by extending its action as a metabolic signal to the main organ at the fetomaternal interface: the placenta.

  18. Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and Regulated by Interleukin-6 Deficiency in Mouse Placenta

    Science.gov (United States)

    Pazos, Patricia; Lima, Luis; Diéguez, Carlos; García, María C.

    2014-01-01

    The placenta produces a number of signaling molecules including metabolic and reproductive hormones as well as several inflammatory mediators. Among them, Interleukin-6 (IL-6), a well-known immune and metabolic regulator, acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. IL-6 interacts with key hypothalamic neuropeptidergic systems controlling energy homeostasis such as those producing the orexigenic/anabolic: neuropeptide Y (NPY) and agouti-related peptide (AgRP) and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART). Human and rat placenta have been identified as source of these neuropeptides, but their expression and regulation in murine placental tissues remain unknown. Therefore, placental mRNA levels of IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days 13, 15, and 18) were analyzed by real time PCR, as were the effect of IL-6 deficiency (IL-6 knockout mice) on their placental expression. Our results showed that placenta-derived neuropeptides were regulated by gestational age and IL-6 throughout the second half of mouse pregnancy. These data suggest that IL-6 may participate in the fine tune control of energy balance during pregnancy by extending its action as a metabolic signal to the main organ at the fetomaternal interface: the placenta. PMID:24744782

  19. Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and Regulated by Interleukin-6 Deficiency in Mouse Placenta.

    Science.gov (United States)

    Pazos, Patricia; Lima, Luis; Diéguez, Carlos; García, María C

    2014-01-01

    The placenta produces a number of signaling molecules including metabolic and reproductive hormones as well as several inflammatory mediators. Among them, Interleukin-6 (IL-6), a well-known immune and metabolic regulator, acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. IL-6 interacts with key hypothalamic neuropeptidergic systems controlling energy homeostasis such as those producing the orexigenic/anabolic: neuropeptide Y (NPY) and agouti-related peptide (AgRP) and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART). Human and rat placenta have been identified as source of these neuropeptides, but their expression and regulation in murine placental tissues remain unknown. Therefore, placental mRNA levels of IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days 13, 15, and 18) were analyzed by real time PCR, as were the effect of IL-6 deficiency (IL-6 knockout mice) on their placental expression. Our results showed that placenta-derived neuropeptides were regulated by gestational age and IL-6 throughout the second half of mouse pregnancy. These data suggest that IL-6 may participate in the fine tune control of energy balance during pregnancy by extending its action as a metabolic signal to the main organ at the fetomaternal interface: the placenta.

  20. Interleukin-6 and neopterin levels in the serum and saliva of patients with Lichen planus and oral Lichen planus.

    Science.gov (United States)

    Abdel-Haq, Ayman; Kusnierz-Cabala, Beata; Darczuk, Dagmara; Sobuta, Eliza; Dumnicka, Paulina; Wojas-Pelc, Anna; Chomyszyn-Gajewska, Maria

    2014-11-01

    Lichen planus together with its oral variant is a chronic, inflammatory disease of the skin and the mucosa of unclear aetiology and with an unpredictable course that still poses a major problem in terms of diagnosis and treatment. The objective of this study was to assess the concentrations of interleukin-6 (IL-6) and neopterin in saliva and serum of patients with lichen planus (including reticular and erosive form of oral lichen planus) and to compare them with the concentrations observed in healthy controls. The study material comprised serum and saliva samples from 56 patients diagnosed with lichen planus and 56 healthy volunteers. The ELISA test was used to measure concentrations of IL-6 and neopterin in the serum and saliva of the study participants. The concentrations of IL-6 in saliva and serum of patients with lichen planus were significantly higher than in controls (P = 0.0002; P lichen planus had significantly higher IL-6 concentrations in their saliva compared to patients with reticular form of disease (P = 0.01). The concentrations of neopterin were significantly higher in the serum but not in saliva of lichen planus patients vs. controls (P lichen planus as well as the salivary concentrations of IL-6. The differences observed in IL-6 levels in patients with erosive-atrophic forms of oral lichen planus may indicate a substantial role played by the cytokine in the disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. The moderating role of job resources in the relationship between job demands and interleukin-6 in an Italian healthcare organization.

    Science.gov (United States)

    Falco, Alessandra; Dal Corso, Laura; Girardi, Damiano; De Carlo, Alessandro; Comar, Manola

    2018-02-01

    In this study we examined the association between job demands (JD), job resources (JR), and serum levels of a possible biomarker of stress, the pro-inflammatory cytokine interleukin-6 (IL-6). According to the buffer hypothesis of the Job Demands-Resources (JD-R) model, we expected that job resources-defined as job autonomy and social support from supervisor-might buffer the relationship between job demands, defined as emotional demands and interpersonal conflict with colleagues, and IL-6. Data from 119 employees in an Italian public healthcare organization (acute care hospital) were analyzed using multiple regression. In predicting IL-6, the interactions between emotional demands and JR and between interpersonal conflict with colleagues and job autonomy (but not social support) were significant, after controlling for the effect of age and gender. The association between JD and IL-6 was stronger for individuals with low levels of JR, so that levels of IL-6 were highest when JD were high and JR were low. Overall, these results are consistent with the buffer hypothesis of the JD-R model and also extend previous research, showing that the exposure to stressful situations at work, measured as high JD and low JR, is associated with higher levels of IL-6 in hospital employees. © 2017 Wiley Periodicals, Inc.

  2. Serum and Urinary Interleukin-6 in Assessment of Renal Activity in Egyptian Patients with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Rawhya R. EL-Shereef

    2016-01-01

    Full Text Available Aim of the Work This study investigates whether serum and urinary interleukin-6 (IL-6 represent an early marker of kidney involvement and assesses the difference between them and renal biopsy in lupus nephritis (LN. Patients and Methods A total of 60 systemic lupus erythematosus (SLE patients were compared to 20 healthy controls. Urinary and serum IL-6 were measured in both patients and controls. In addition, renal biopsy was done prior or shortly after urine and blood sampling; the results were classified according to the International Society of Nephrology/Renal Pathology Society classification of LN by recording the activity score and chronicity score for each sample. Results There was a significant higher level of urinary IL-6 in the SLE patients with biopsy-proven LN than in those without LN and those of the control group. However, no significant difference was reported between the three groups as regards serum IL-6. A strong positive correlation was found between urinary IL-6 and renal disease activity based on the renal SLE disease activity index (SLEDAI score with no significant correlation regarding the extra renal SLEDAI. Urinary IL-6 was positively correlated with renal biopsy results and with its activity scores but weakly correlated with the chronicity scores. Conclusion Urinary IL-6 may provide a simple noninvasive potential marker of disease activity of renal involvement in adult patients with SLE.

  3. Soluble CD163 and interleukin-6 are increased in aqueous humour from patients with endothelial rejection of corneal grafts

    DEFF Research Database (Denmark)

    Funding, Mikkel; Vorum, Henrik; Nexø, Ebba

    2005-01-01

    PURPOSE: To evaluate soluble CD163 (sCD163) as a new marker of macrophage activity in aqueous humour from patients with corneal rejection and to investigate correlations between sCD163, the CD163 inducing interleukin-6 (IL-6), and albumin; to investigate whether increases in sCD163 and IL-6 levels...... with uncomplicated corneal grafts. The presence of sCD163 was investigated by immunoprecipitation and immunoblotting. The concentrations of sCD163, IL-6 and albumin were measured by ELISA. RESULTS: Soluble CD163 was detected in aqueous humour from patients with corneal rejection. Soluble CD163, IL-6 and albumin were......CD163 were related to the outcome of the corneal rejection. CONCLUSIONS: Both sCD163 and IL-6 are present in high levels in aqueous humour from patients with rejection of corneal grafts. Our data suggest that IL-6 is produced locally, whereas sCD163 is at least partly derived from influx from plasma....

  4. Influence of corticosteroid pulse therapy on the serum levels of soluble interleukin 2 receptor, interleukin 6 and interleukin 8 in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    van den Brink, H. R.; van Wijk, M. J.; Geertzen, R. G.; Bijlsma, J. W.

    1994-01-01

    To investigate the influence of corticosteroid pulse (CP) therapy on soluble interleukin 2 receptor (sIL-2R), interleukin 6 (IL-6) and IL-8 levels in patients with active rheumatoid arthritis (RA). Twenty-five patients with active RA were studied before and after treatment with intravenous CP

  5. Stearidonic and eicosapentaenoic acids inhibit interleukin-6 expression in ob/ob mouse adipose stem cells via toll-like receptor-2-mediated pathways

    Science.gov (United States)

    Increases in adipose tissue weight positively correlates with increased circulating inflammatory cytokines such as interleukin-6 (IL-6). We previously have shown that adipose stem cell produce significantly higher levels of IL-6 when compared to other cell types in the adipose tissue in genetically ...

  6. Late midlife C-reactive protein and interleukin-6 in middle aged danish men in relation to body size history within and across generations

    DEFF Research Database (Denmark)

    Pedersen, Jolene Lee Masters; Budtz-Jørgensen, Esben; Mortensen, Erik Lykke

    2016-01-01

    OBJECTIVE: The aim was to estimate the effects of ponderal index at birth and body mass index (BMI) in early adulthood on C-reactive protein (CRP) and interleukin-6 (IL-6) and to quantify the effects through subsequent measures of body size. In a subanalysis, the contributions of maternal BMI to ...

  7. Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus

    NARCIS (Netherlands)

    Gardenghi, Sara; Renaud, Tom M; Meloni, Alessandra; Casu, Carla; Crielaard, Bart J; Bystrom, Laura M; Greenberg-Kushnir, Noa; Sasu, Barbra J; Cooke, Keegan S; Rivella, Stefano

    2014-01-01

    Anemia of inflammation (AI) is commonly observed in chronic inflammatory states and may hinder patient recovery and survival. Induction of hepcidin, mediated by interleukin 6, leads to iron-restricted erythropoiesis and anemia. Several translational studies have been directed at neutralizing

  8. Interleukin-6 production by human liver (myo)fibroblasts in culture. Evidence for a regulatory role of LPS, IL-1 beta and TNF alpha

    NARCIS (Netherlands)

    Tiggelman, A. M.; Boers, W.; Linthorst, C.; Brand, H. S.; Sala, M.; Chamuleau, R. A.

    1995-01-01

    Interleukin-6 is a major trigger for the synthesis of acute phase proteins by liver parenchymal cells. Acute phase proteins may contribute to the regulation of liver fibrosis by inhibition of proteases (e.g. collagenase) and by binding of cytokines. Since liver (myo)fibroblasts play an important

  9. The decrease in nonsplenic interleukin-6 (IL-6) production after splenectomy indicates the existence of a positive feedback loop of IL-6 production during endotoxemia in dogs

    NARCIS (Netherlands)

    Moeniralam, H. S.; Bemelman, W. A.; Endert, E.; Koopmans, R.; Sauerwein, H. P.; Romijn, J. A.

    1997-01-01

    The spleen is involved in endotoxin-induced interleukin-6 (IL-6) production. To quantitate the relative contribution of the spleen to endotoxin-induced IL-6 production, we studied the effect of endotoxin (1.0 microg/kg of body weight) in control dogs (n = 7) and splenectomized dogs (n = 7). Blood

  10. Induction of interleukin-6 production by ultraviolet radiation in normal human epidermal keratinocytes and in a human keratinocyte cell line is mediated by DNA damage

    NARCIS (Netherlands)

    Petit-Frère, C.; Clingen, P.H.; Grewe, M.; Krutmann, J.; Roza, L.; Arlett, C.F.; Green, M.H.L.

    1998-01-01

    The sunburn reaction is the most common consequence of human exposure to ultraviolet radiation (UVR), and is mediated at least in part by interleukin- 6 (IL-6). The aim of this study was to determine if DNA is a major chromophore involved in the induction of IL-6 following UV irradiation of a human

  11. Association of interleukin-6-572C/G gene polymorphism and serum or cerebrospinal fluid interleukin-6 level with enterovirus 71 encephalitis in Chinese Han patients with hand, foot, and mouth disease.

    Science.gov (United States)

    Yuan, Aiyun; Li, Jian; Liu, Peipei; Chen, Zongbo; Hou, Mei; Wang, Jinju; Han, Zhenliang

    2015-04-01

    Interleukin-6 (IL-6), as one of pro-inflammatory cytokines, plays a key role in Enterovirus 71 (EV71) encephalitis. We investigated the association of IL-6-572C/G polymorphism and serum or cerebrospinal fluid (CSF) IL-6 level with EV71 encephalitis in patients with hand, foot, and mouth disease (HFMD). This study was carried out in 59 Chinese Han patients with EV71 encephalitis, 128 EV71-related HFMD without complications, and 232 controls. The IL-6-572C/G polymorphism was detected by polymerase chain reaction-restricted fragment length polymorphism gene analysis. Serum or CSF IL-6 levels were determined using a commercial enzyme-linked immunosorbent assay. The patients with EV71 encephalitis had a higher frequency of IL-6-572GG/GC genotype compared to the patients with EV71-related HFMD without encephalitis complications (40.7 vs. 15.6 %, odds ratio (OR)=3.70, 95 % confidence interval (CI)=1.83-7.50, p=0.001). Similarly, the frequency of IL-6-572 G allele among the patients with EV71 encephalitis was also higher than that of patients with EV71-related HFMD without encephalitis complications (23.7 vs. 8.6 %, OR=3.31, 95 % CI=1.80-6.08, pencephalitis. Furthermore, G carriers (GG + GC) (10.6 ±.29 mg/l) had significantly higher blood CRP levels compared to CC homozygotes (9.31 ± 1.93 mg/l) in patients with EV71 encephalitis (p=0.005). These findings suggested that IL-6-572 G allele was significantly associated with the susceptibility to EV71 encephalitis in Chinese Han patients, and IL-6-572 G allele might elevate the risk to EV71 encephalitis.

  12. The study of the effect of World Health Organization recommended physical activity program on C- reactive protein and interleukin-6 in middle-aged men

    Directory of Open Access Journals (Sweden)

    Ahmad Azad

    2013-04-01

    Full Text Available Background: Based on the World Health Organization (WHO proposition, 5 days a week and 30 minutes a day of aerobic physical activity has numerous healthy effects for middle-aged and adult population. However, to date the anti inflammatory effect of this program has not been studied. The purpose of this study was to investigate the effect of 16 weeks of the WHO purposed physical activity program on C-reactive protein and interleukin-6 in middle-aged men. Material and Methods: 30 middle-aged men with C-reactive protein and interleukin-6 levels higher than the predicted values participated in this study. The subjects randomized to three groups: control(n=10, one training session per day(n=10, 16 weeks, 5 days a week, 30 minutes a day tread mill running, with70-80% of HRmax , and two training sessions per day(n=10, 16 weeks, 5 days a week, 2×15 minutes a day tread mill running, with70-80% of HRmax. Pre and post exercise C-reactive protein (fasting, interleukin-6(fasting, BMI and VO2max were measured. Data were analyzed with paired and one sample t-test and variance analysis. Results: Both training methods caused significant (p<0.05 decrease in C-reactive protein, interleukin-6 and BMI, and significant (p<0.05 increase in VO2max in comparison with the control group. Conclusion: 16 weeks of the WHO proposed physical activity program, either one session per day or two sessions per day, can lead to C-reactive protein and interleukin-6 reduction in middle-age men.

  13. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study

    Science.gov (United States)

    Gimeno, David; Kivimäki, Mika; Brunner, Eric J.; Elovainio, Marko; De Vogli, Roberto; Steptoe, Andrew; Kumari, Meena; Lowe, Gordon D.O.; Rumley, Ann; Marmot, Michael G.; Ferrie, Jane E.

    2009-01-01

    Background A lack of longitudinal studies has made it difficult to establish the direction of associations between circulating concentrations of low-grade chronic inflammatory markers, such as C-reactive protein and interleukin-6, and cognitive symptoms of depression. The present study sought to assess whether C-reactive protein and interleukin-6 predict cognitive symptoms of depression or whether these symptoms predict inflammatory markers. Methods A prospective occupational cohort study of British white-collar civil servants: Whitehall II. Serum C-reactive protein, interleukin-6 and cognitive symptoms of depression were measured at baseline in 1991-3 and at follow-up in 2002-4, an average follow-up of 11.8 years. Symptoms of depression were measured with 4 items describing cognitive symptoms of depression from the General Health Questionnaire. The number of participants varied between 3339 and 3070 (mean age 50 years, 30% women) depending on the analysis. Results Baseline C-reactive protein (β=0.046, p=0.004) and interleukin-6 (β=0.046, p=0.005) predicted cognitive symptoms of depression at follow-up, while baseline symptoms of depression did not predict inflammatory markers at follow-up. After full adjustment for sociodemographic, behavioural and biological risk factors, health conditions and medication use, baseline C-reactive protein (β=0.038, p=0.036) and interleukin-6 (β=0.041, p=0.018) remained predictive of cognitive symptoms of depression at follow-up. Conclusions These findings suggest that inflammation precedes depression at least with regard to the cognitive symptoms of depression. PMID:18533059

  14. Age-Related Increased Prevalence of Asthma and Nasal Polyps in Chronic Rhinosinusitis and Its Association with Altered IL-6 Trans-Signaling

    Science.gov (United States)

    Kim, Dae Woo; Lee, Sun H.; Kolliputi, Narasaiah; Hong, Seung J.; Suh, Lydia; Norton, James; Hulse, Kathryn E.; Seshadri, Sudarshan; Conley, David B.; Kern, Robert C.; Tan, Bruce K.; Peters, Anju; Grammer, Leslie C.; Schleimer, Robert P.

    2015-01-01

    We report that S100 proteins were reduced in patients with chronic rhinosinusitis (CRS). S100A8/9, which is important in epithelial barrier function, was particularly decreased in elderly patients with CRS. Epithelial expression of S100A8/9 is partly regulated by the IL-6 trans-signaling pathway. The goal of this study was to investigate whether or not age-related reduction of S100A8/9 in CRS is associated with blunting of IL-6 trans-signaling. The levels of IL-6, soluble IL-6 receptor (sIL-6R), soluble gp130 (sgp130), and S100A8/9 from control subjects (n = 10), and patients with CRS without nasal polyps (n = 13) and those with CRS with nasal polyps (CRSwNP) (n = 14), were measured by ELISA. Age-related differences in the level of each protein were investigated. Normal human bronchial epithelial cells were cultured in air–liquid interface and stimulated with IL-6/sIL-6R and tumor necrosis factor (TNF)-α with or without the addition of sgp130, a natural inhibitor of IL-6 trans-signaling. There was a significant age-related decline in S100A8/9 and an increase in sgp130 in nasal tissue samples from patients with CRSwNP, although there was no age-related difference in IL-6/sIL-6R production. Additionally, expression of the S100A8/9 gene and protein was increased significantly by IL-6/sIL-6R plus TNF-α in normal human bronchial epithelial cells. This increase was blocked by sgp130. These results suggest that increased sgp130 in older patients may inhibit IL-6 trans-signaling, impair barrier function, and decrease S1008/9 production in elderly patients with CRSwNP. Restoration of barrier function by targeting sgp130 may be a novel treatment strategy. PMID:26266960

  15. An insight into the relationships between prohepcidin, iron deficiency anemia, and interleukin-6 values in pediatric Helicobacter pylori gastritis.

    Science.gov (United States)

    Emiralioglu, Nagehan; Yenicesu, Idil; Sari, Sinan; Egritas, Odul; Poyraz, Aylar; Pasaoglu, Ozge Tugce; Celik, Bulent; Dalgic, Buket

    2015-07-01

    The link between Helicobacter pylori and iron deficiency (ID) or iron deficiency anemia (IDA) has been investigated recently. We suggested that IDA/ID associated with H. pylori infection might be mediated by inflammation-driven hepcidin production. Patients with complaints of recurrent abdominal pain and dyspepsia aged between 7-16 years were included in this study. Patients were divided into two groups according to H. pylori status in upper gastrointestinal endoscopy. Group I who had H. pylori gastritis (n=50) received triple antibiotic therapy. Group II (n=50) who had H. pylori-negative gastritis only received proton pump inhibitor. Thirty healthy children with the similar age and gender were included in the study as a control group. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, prohepcidin and interleukin-6 (IL-6) values were evaluated in all children at the first visit. Initial tests were repeated after H. pylori eradication. Initial levels of ferritin (p=0.002), prohepcidin (p=0.003), and IL-6 (p=0.004) were found significantly lower in group I compared to group II and the control group. The mean prohepcidin level was lower in the anemic H. pylori-positive group than in non-anemic H. pylori-positive group; however, the difference was not statistically significant. While significant increases in hematocrit and mean corpuscular volume were observed, no significant difference was found in serum ferritin, prohepcidin, or IL-6 level after eradication treatment in H. pylori-positive group. H. pylori-induced gastritis appears to cause an increase in prohepcidin levels and a decrease in ferritin levels, supporting our hypothesis; but this relationship has not been proven.

  16. Association of Interleukin 6 gene polymorphisms with genetic susceptibilities to spastic tetraplegia in males: a case-control study.

    Science.gov (United States)

    Chen, Mingjie; Li, Tongchuan; Lin, Sheyu; Bi, Dan; Zhu, Dengna; Shang, Qing; Ma, Caiyun; Wang, Honglian; Wang, Lei; Zhang, Yiting; He, Lin; Zhu, Changlian; Xing, Qinghe

    2013-03-01

    Cerebral palsy (CP) is a group of non-progressive motor impairment and permanent disorders causing limitation of activity and abnormal posture. It may be caused by infection (such as chorioamnionitis), asphyxia or multiple genetic factors. The Interleukin 6 gene (IL6) was suggested to be involved in the susceptibilities to CP risk as a kind of proinflammatory cytokine. To explore the genetic association between the polymorphisms of the IL6 gene and CP in the Chinese population. A total of 542 CP patients and 483 healthy control children were recruited in this study to detect five single nucleotide polymorphisms (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL6 locus. Genotyping of SNPs was performed by the MassArray platform-based genotyping approach. The SHEsis program was applied to analyze the genotyping data. Of the five selected SNPs, no significant allelic and genotypic association was found between CP patients and controls. However, subgroup analysis found significant differences in allele frequencies between spastic tetraplegia in males compared with controls at rs1800796 (OR=1.39, P=0.033, P=0.099 after SNPSpD correction) and rs2069837 (OR=1.58, P=0.012, P=0.035 after SNPSpD correction). The frequencies of the C allele of rs1800796 and the A allele of rs2069837 were greater in males with spastic tetraplegia than in the controls. The two SNPs haplotype rs1800796 (G) - rs2069837 (G) were also associated with a decreased risk of spastic tetraplegia in males (OR=0.619, P=0.009, P=0.027 after Bonferroni correction). Genetic variation of the IL6 gene may influence susceptibility to spastic tetraplegia in males and its role in cerebral palsy deserves further evaluation in a large-scale and well-designed study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Effects of Minocycline on Urine Albumin, Interleukin-6, and Osteoprotegerin in Patients with Diabetic Nephropathy: A Randomized Controlled Pilot Trial.

    Directory of Open Access Journals (Sweden)

    Anuja P Shah

    Full Text Available We tested minocycline as an anti-proteinuric adjunct to renin-angiotensin-aldosterone system inhibitors (RAASi in diabetic nephropathy (DN and measured urinary biomarkers to evaluate minocycline's biological effects.Prospective, single center, randomized, placebo-controlled, intention-to-treat pilot trial. Inclusion. Type 2 diabetes/DN; Baseline creatinine clearance >30 mL/min; proteinuria ≥1.0 g/day; Age ≥30 years; BP <150/95 mm Hg; intolerant of/at maximum RAASi dose. Protocol. 3-wk screening; Baseline randomization; Urine and blood measures at months 1, 2, 4, and Month 6 study completion. Urine interleukin-6 (IL-6 and osteoprotegerin were measured in a subset. Primary outcome. Natural log of urine protein/creatinine (ln U P:Cr ratio at Month 6 vs Baseline.30 patients completed the study. The 15% decline in U P: Cr in minocycline patients (6 month P:Cr ÷ Baseline P:Cr, 0.85 vs. 0.92 was not significant (p = 0.27. Creatinine clearance did not differ in the 2 groups. Urine IL-6:Cr (p = 0.03 and osteoprotegerin/Cr (p = 0.046 decrements were significant. Minocycline modified the relationship between urine IL-6 and proteinuria, suggesting a protective biological effect.Although the decline in U P:Cr in minocycline patients was not statistically significant, the significant differences in urine IL-6 and osteoprotegerin suggest that minocycline may confer cytoprotection in patients with DN, providing a rationale for further study.Clinicaltrials.gov NCT01779089.

  18. Manipulation of flaxseed inhibits tumor necrosis factor-alpha and interleukin-6 production in ovarian-induced osteoporosis.

    Science.gov (United States)

    Abdelkarem, Hala M; Abd El-Kader, Madeha M; Kasem, Seham A

    2011-04-01

    To evaluate the potential effects of whole flaxseed (FS), and/or flax oil (FO) incorporation into the diet on the level of pro-inflammatory cytokines in ovariectomized (OVX) rats model of osteoporosis. This study was performed in the Food Science & Agriculture Collage, King Saud University, Kingdom of Saudi Arabia from October to December 2009. Forty-eight, 3-month-old female Sprague-Dawley rats were randomly divided into 6 groups: Group 1 - sham + control diet; Group 2 - OVX rats + basal diet; Group 3 - OVX + 20% whole FS; Group 4 - OVX rats + 40% FS; Group 5 - OVX rats + 5% FO; Group 6 - OVX rats + 10% FO. All OVX rats underwent bilateral ovariectomy. The experiment was continued for 2 months. Serum bone alkaline phosphatase (B-ALP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), calcium (Ca), phosphorous (P), and magnesium (Mg) were measured. A significant increase of serum IL-6 and TNF-alpha concentrations were observed between OVX rats when compared with Group 1, while there was no significant difference in the activity of B-ALP, serum Ca, P, and Mg among all groups. A remarkable significant decrease of serum levels of IL-6 and TNF-alpha was observed in the group of rats that were fed with FS (Groups 3 and 4) and FO (Groups 5 and 6). This study suggests that FS and FO might be useful in the prevention of estrogen-deficiency induced osteoporosis via decreasing osteoclastogenesis. Further studies are needed to demonstrate their efficacy in humans by using bioactive components of FS, and to clarify their mechanism of action.

  19. Alantolactone Improves Prolonged Exposure of Interleukin-6-Induced Skeletal Muscle Inflammation Associated Glucose Intolerance and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Minjee Kim

    2017-06-01

    Full Text Available The pro-inflammatory cytokine, Interleukin-6 (IL-6, has been proposed to be one of the mediators that link chronic inflammation to glucose intolerance and insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin action in the skeletal muscle. However, few studies have investigated the effect of long-term treatment of IL-6, leading to glucose intolerance and insulin resistance. In the present study, we observed protective effects of alantolactone, a sesquiterpene lactone isolated from Inula helenium against glucose intolerance and insulin resistance induced by prolonged exposure of IL-6. Alantolactone has been reported to have anti-inflammatory and anti-cancer effects through IL-6-induced signal transducer and activator of transcription 3 (STAT3 signaling pathway. The relationship between IL-6 exposure and expression of toll-like receptor 4 (TLR4, involved in inflammation in the skeletal muscle, and the underlying mechanisms were investigated. We observed maximum dysregulation of glucose uptake after 40 ng/ml IL-6 induction for 24 h in L6 myotubes. Prolonged IL-6 exposure suppressed glucose uptake regulating alpha serine/threonine-protein kinase (AKT phosphorylation; however, pretreatment with alantolactone activated AKT phosphorylation and improved glucose uptake. Alantolactone also attenuated IL-6-stimulated STAT3 phosphorylation, followed by an increase in expression of negative regulator suppressor of cytokine signaling 3 (SOCS3. Furthermore, IL-6-induced expression of pathogen recognition receptor, TLR4, was also suppressed by alantolactone pretreatment. Post-silencing of STAT3 using siRNA approach, IL-6-stimulated siRNA-STAT3 improved glucose uptake and suppressed TLR4 gene expression. Taken together, we propose that, as a STAT3 inhibitor, alantolactone, improves glucose regulation in the skeletal muscle by inhibiting IL-6-induced STAT3-SOCS3 signaling followed by inhibition of the TLR4 gene expression. Therefore

  20. Mimosine suppresses the PGF2α-induced synthesis of osteoprotegerin but not interleukin-6 in osteoblasts.

    Science.gov (United States)

    Kuroyanagi, Gen; Otsuka, Takanobu; Yamamoto, Naohiro; Kainuma, Shingo; Ohguchi, Reou; Fujita, Kazuhiko; Matsushima-Nishiwaki, Rie; Kozawa, Osamu; Tokuda, Haruhiko

    2016-02-01

    Mimosine, a plant amino acid, is known to act as a normoxic inducer of hypoxia-inducible factor (HIF). Previous research has suggested that HIF plays important roles in angiogenesis-osteogenesis coupling and bone metabolism. We previously reported that prostaglandin F2α (PGF2α) induced osteoprotegerin synthesis through p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. We have also demonstrated that PGF2α induced the synthesis of interleukin-6 (IL-6) via p38 MAP kinase and p44/p42 MAP kinase but not SAPK/JNK in these cells. In the present study, we investigated the effects of mimosine on the PGF2α-induced synthesis of osteoprotegerin or IL-6 in MC3T3-E1 cells. We found that deferoxamine, another inducer of HIF, as well as mimosine, upregulated the protein levels of HIF-1α. Both mimosine and deferoxamine significantly suppressed the PGF2α-induced release of osteoprotegerin, and the mRNA expression level, without markedly affecting PGF2α-induced IL-6 release. Both mimosine and deferoxamine, by themselves, induced the release of vascular endothelial growth factor. The phosphorylation of p38 MAP kinase, p44/p42 MAP kinase or SAPK/JNK induced by PGF2α was not markedly affected by either mimosine or deferoxamine. Thus, the results of the present study strongly suggest that mimosine, a normoxic inducer of HIF, inhibits the PGF2α‑induced osteoprotegerin synthesis without affecting the IL-6 synthesis in osteoblasts.

  1. Synergistic augmentation of ATP-induced interleukin-6 production by arsenite in HaCaT cells.

    Science.gov (United States)

    Sumi, Daigo; Asao, Masashi; Okada, Hideta; Yogi, Kuniko; Miyataka, Hideki; Himeno, Seiichiro

    2016-06-01

    Chronic arsenic exposure causes cutaneous diseases such as hyperkeratosis and skin cancer. However, little information has been available regarding the molecular mechanisms underlying these symptoms. Because extracellular ATP and interleukin-6 (IL-6) are involved in pathological aspects of cutaneous diseases, we examined whether sodium arsenite (As(III)) affects ATP-induced IL-6 production in human epidermal keratinocyte HaCaT cells. The results showed that the addition of As(III) into the medium of HaCaT cells dose dependently increased the production of IL-6 induced by extracellular ATP, although As(III) alone had no effect on IL-6 production. To elucidate the mechanism of the synergistic effect of As(III) on IL-6 production by extracellular ATP, we next examined the phosphorylation of p38, ERK and epidermal growth factor receptor (EGFR), since we found that these signaling molecules were stimulated by exposure to extracellular ATP. The results indicated that ATP-induced phosphorylation of p38, ERK and EGFR was synergistically enhanced by co-exposure to As(III). To clarify the mechanisms underlying the enhanced phosphorylation of p38, ERK and EGFR by As(III), we explored two possible mechanisms: the inhibition of extracellular ATP degradation and the inhibition of protein tyrosine phosphatases (PTPs) activity by As(III). The degradation of extracellular ATP was not changed by As(III), whereas the activity of PTPs was significantly inhibited by As(III). Our results suggest that As(III) augments ATP-induced IL-6 production in HaCaT cells through enhanced phosphorylation of the EGFR and p38/ERK pathways, which is associated with the inhibition of PTPs activity.

  2. Influence of low frequency magnetic field used in magnetotherapy on interleukin 6 (IL-6 contents in rat heart and brain

    Directory of Open Access Journals (Sweden)

    Elżbieta Ciejka

    2017-08-01

    Full Text Available Background: The human population is exposed ever more frequently to magnetic fields (MF. This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF used in magnetotherapy on the concentration of interleukin 6 (IL-6 in rat heart and brain. Material and Methods: The male rats were randomly divided into 3 experimental groups: group I – control, without contact with magnetic field; group II − exposed to bipolar, rectangular magnetic field 40 Hz, induction “peak-to-peak” 7 mT 30 min/day for 2 weeks; and group III − exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. Results: Exposure to ELFMF: 40 Hz, induction “peak-to-peak” 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05 and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05. Conclusions: The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4:517–523

  3. In vivo screening for secreted proteins that modulate glucose handling identifies interleukin-6 family members as potent hypoglycemic agents.

    Directory of Open Access Journals (Sweden)

    Chen Amy Chen

    Full Text Available Diabetes is a disease of abnormal glucose homeostasis characterized by chronic hyperglycemia and a broad array of consequent organ damage. Because normal glucose homeostasis is maintained by a complex interaction between behavior (feeding and physical activity and metabolic activity that is modulated by inter-organ signaling through secreted factors, disease modeling in vitro is necessarily limited. In contrast, in vivo studies allow complex metabolic phenotypes to be studied but present a barrier to high throughput studies. Here we present the development of a novel in vivo screening platform that addresses this primary limitation of in vivo experimentation. Our platform leverages the large secretory capacity of the liver and the hepatocyte transfection technique of hydrodynamic tail vein injection to achieve supraphysiologic blood levels of secreted proteins. To date, the utility of hydrodynamic transfection has been limited by the deleterious impact of the variable transfection efficiency inherent to this technique. We overcome this constraint by co-transfection of a secreted luciferase cDNA whose product can be easily monitored in the blood of a living animal and used as a surrogate marker for transfection efficiency and gene expression levels. To demonstrate the utility of our strategy, we screened 248 secreted proteins for the ability to enhance glucose tolerance. Surprisingly, interleukin-6 and several of its family members but not other well-recognized insulin sensitizing agents were identified as potent hypoglycemic factors. We propose this experimental system as a powerful and flexible in vivo screening platform for identifying genes that modulate complex behavioral and metabolic phenotypes.

  4. Comparison of umbilical cord interleukin-6 in preterm infants with premature rupture of membranes and intact membranes

    International Nuclear Information System (INIS)

    Gharebaghi, Manizheh M.; Peirovifar, A.; Gharebaghi, Parvin M.

    2008-01-01

    Objective was to compare inflammatory mediators in the cord blood of premature newborn infants with premature rupture of membranes (PROM) and intact membranes. Eighty-nine premature neonates with gestational age of 27-34 weeks that delivered in Ghaem Hospital in Mashhad, Iran from June 2005 to March 2006 were enrolled in a prospective observational study and their umbilical cord plasma was collected at birth. They were allocated into 2 groups (45 patients with PROM and 44 neonates with intact membranes). Interleukin-6 (IL-6) and C-reactive protein (CRP) levels were measured in cord plasma by the enzyme linked immunoassay (ELISA) method. Mean cord plasma IL-6 levels in preterm neonates with PROM was 205.71 pg/ml and in neonates with intact membranes was 33.3 pg/ml for IL-6 (p=0.000). The mean cord blood CRP level in newborns was 10.2 ug/ml, and in those with intact membranes was 1.6 ug/ml and in those with intact membranes was 1.6 ug/ml (p=0.41). Early onset sepsis was more frequent in infants with PROM than premature infants with intact membrane (38% versus 10%, p=0.001). In neonates with PROM, the mean cord blood IL-6 level was significantly higher in septic newborns (414.28 versus 40.44 pg/ml, p=0.000). The premature newborn infants with PROM had increased IL-6 levels in cord blood, which was significantly higher in neonates that developed early onset sepsis. (author)

  5. Synergistic Effect of Radiation and Interleukin-6 on Hepatitis B Virus Reactivation in Liver Through STAT3 Signaling Pathway

    International Nuclear Information System (INIS)

    Chou, C.H.; Chen, P.-J.; Jeng, Y.-M.; Cheng, A.-L.; Huang, L.-R.; Cheng, J.C.-H.

    2009-01-01

    Purpose: Hepatitis B virus (HBV) reactivation can occur after radiotherapy (RT) for hepatobiliary malignancies. Our previous in vitro culture study identified interleukin-6 (IL-6) as the main bystander mediator of RT-induced HBV replication. We attempted to examine the molecular mechanism in HBV-transgenic mice. Methods and materials: HBV transgenic mice were treated with whole liver RT (4 Gy daily for 5 days) with or without administration of IL-6 (400 ng twice daily for 15 days). The serum level of HBV DNA was measured using real-time polymerase chain reaction, and the IL-6 concentration was measured using enzyme-linked immunosorbent assay. The intensity of immunostaining with antibodies to HBV core protein and phosphorylated signal transducer and activator of transcription (STAT)3 in the mouse liver was qualitatively analyzed. HepG2.2.15 cells (a human hepatoblastoma cell line that persistently produces HBV DNA) were used to investigate the molecular role of IL-6 plus RT in HBV reactivation. Results: HBV reactivation was induced in vivo with IL-6 plus RT (5.58-fold) compared with RT alone (1.31-fold, p = .005), IL-6 alone (1.31-fold, p = .005), or sham treatment (1.22-fold, p = .004). HBV core protein staining confirmed augmentation of intrahepatic HBV replication. IL-6 plus RT-induced HBV DNA replication in HepG2.2.15 cells was suppressed by the STAT3 inhibitor AG490 and by transfection with dominant-negative STAT3 plasmid. Phosphorylated STAT3 staining was strongest in liver tissue from mice treated with IL-6 plus RT. The mobility shift assay demonstrated that reactivation was mediated through the interaction of phosphorylated STAT3/hepatocyte nuclear factor-3 complex with HBV enhancer 1. Conclusion: RT to the liver and longer sustained IL-6 induced HBV reactivation through the STAT3 signal transduction pathway.

  6. Secretion of an immunoreactive single-chain variable fragment antibody against mouse interleukin 6 by Lactococcus lactis.

    Science.gov (United States)

    Shigemori, Suguru; Ihara, Masaki; Sato, Takashi; Yamamoto, Yoshinari; Nigar, Shireen; Ogita, Tasuku; Shimosato, Takeshi

    2017-01-01

    Interleukin 6 (IL-6) is an important pathogenic factor in development of various inflammatory and autoimmune diseases and cancer. Blocking antibodies against molecules associated with IL-6/IL-6 receptor signaling are an attractive candidate for the prevention or therapy of these diseases. In this study, we developed a genetically modified strain of Lactococcus lactis secreting a single-chain variable fragment antibody against mouse IL-6 (IL6scFv). An IL6scFv-secretion vector was constructed by cloning an IL6scFv gene fragment into a lactococcal secretion plasmid and was electroporated into L. lactis NZ9000 (NZ-IL6scFv). Secretion of recombinant IL6scFv (rIL6scFv) by nisin-induced NZ-IL6scFv was confirmed by western blotting and was optimized by tuning culture conditions. We found that rIL6scFv could bind to commercial recombinant mouse IL-6. This result clearly demonstrated the immunoreactivity of rIL6scFv. This is the first study to engineer a genetically modified strain of lactic acid bacteria (gmLAB) that produces a functional anti-cytokine scFv. Numerous previous studies suggested that mucosal delivery of biomedical proteins using gmLAB is an effective and low-cost way to treat various disorders. Therefore, NZ-IL6scFv may be an attractive tool for the research and development of new IL-6 targeting agents for various inflammatory and autoimmune diseases as well as for cancer.

  7. Clinical response to non-surgical periodontal treatment in patients with interleukin-6 and interleukin-10 polymorphisms

    Science.gov (United States)

    Doufexi, Aikaterini-Ellisavet; Kouvatsi, Anastasia

    2017-01-01

    Background Genetic polymorphisms are commonly associated with altered transcriptional activity and possibly make individuals more susceptible to periodontal disease development, increased disease severity and poor treatment outcome. The study aimed to determine the effect of Interleukin-6 (IL-6) -572 G/C (rs1800796) and IL-10 -592 C/A (rs1800872) polymorphisms on the outcomes of non-surgical periodontal therapy in a Caucasian population. Material and Methods Sixty-eight patients with chronic periodontal disease were grouped according to their genotype: IL-6, IL-10, IL-6 and IL-10 susceptible (SCP) and non-susceptible (NSCP). All individuals were clinically evaluated at the first visit, and blood sample were collected from patients after checking the inclusion and exclusion criteria of the study. All patients received non-surgical periodontal therapy from a single-blinded periodontist. Clinical periodontal measurements were repeated 45 days after therapy. Results This population mean aged 47.63 years included 52.2% females and 58.2% non-smokers. Following DNA separation and genotyping, 65.7% of patients were homozygous carriers of the IL-6 - 572G; 49.3% were carriers of the IL-10 -592A- allele (AA and CA genotypes); and 35.8% carried SCP genotypes for both polymorphisms. The clinical parameters after therapy were not associated with the genotype status. The multiple logistic regression analysis did not show any statistically significant association between the genotypes and the variables tested. Conclusions Within the limitations of this longitudinal study, it can be suggested that IL-6 -572 G/C and IL-10 -592 C/A polymorphisms as well as their combination do not influence the outcome of nonsurgical periodontal therapy in Caucasian patients diagnosed with chronic periodontal disease. Key words:Gene polymorphism, genetics, interleukins, periodontal disease, treatment outcome. PMID:28624837

  8. Effect of Grape Seed Extract on Lipid Profile and Expression of Interleukin-6 in Polycystic Ovarian Syndrome Wistar Rat Model

    Directory of Open Access Journals (Sweden)

    Zohreh Salmabadi

    2017-09-01

    Full Text Available Background Polycystic ovary syndrome (PCOS is a common but complex endocrine disorder and is the major cause of anovulation and consequent subfertility. In this study the effect of grape seed extract (GSE on triglyceride (TG, total cholesterol (TC, highdensity lipoprotein-cholestrol (HDL-C, low-density lipoprotein-cholestrol (LDL-C and interleukin-6 (IL-6 in PCOS Wistar rats were assessed. Materials and Methods In this experimental study, 84 adult female Wistar rats were divided into 7 groups (n=12 including control (intact, Sham (estradiol valerate solvent injection, control PCOS and 4 experimental PCOS groups. To induce the syndrome, a single subcutaneous injection of 2 mg estradiol valerate was applied. In experimental groups, PCOS rats were treated with different doses of 50, 75, 100 and 200 mg/kg body weight (BW GSE by intraperitoneal injection for 10 consecutive days. After harvesting blood serum, TG was measured by Glycerol-3-phosphate Oxidase-Peoxidase (GPO- PAP, TC by Cholesterol Oxidase-Peroxidase (CHOD-PAP, and HDL-C by sedimentation method, LDL-C by Friedwald calculation and IL-6 by ELISA method. The serum values of each parameter were analyzed using one-way ANOVA at P≤0.05. Results In all experimental groups significant decrease of visceral fat was obvious as compared with control PCOS group. LDL-C, TC and IL-6 levels in experimental groups, particularly at dose of 50 mg/kg of GSE, were significantly decreased as compared with PCOS group. However, HDL-C levels were not significantly changed. Conclusion : According to the findings of this study, it can be concluded that GSE with its effects on serum TC, LDL-C and IL-6 could reduce the effects of dyslipidemia and inflammation in PCOS rats and improve systemic symptoms of PCOS.

  9. Effect of Grape Seed Extract on Lipid Profile and Expression of Interleukin-6 in Polycystic Ovarian Syndrome Wistar Rat Model.

    Science.gov (United States)

    Salmabadi, Zohreh; Mohseni Kouchesfahani, Homa; Parivar, Kazem; Karimzadeh, Latifeh

    2017-10-01

    Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is the major cause of anovulation and consequent subfertility. In this study the effect of grape seed extract (GSE) on triglyceride (TG), total cholesterol (TC), highdensity lipoprotein-cholestrol (HDL-C), low-density lipoprotein-cholestrol (LDL-C) and interleukin-6 (IL-6) in PCOS Wistar rats were assessed. In this experimental study, 84 adult female Wistar rats were divided into 7 groups (n=12) including control (intact), Sham (estradiol valerate solvent injection), control PCOS and 4 experimental PCOS groups. To induce the syndrome, a single subcutaneous injection of 2 mg estradiol valerate was applied. In experimental groups, PCOS rats were treated with different doses of 50, 75, 100 and 200 mg/kg body weight (BW) GSE by intraperitoneal injection for 10 consecutive days. After harvesting blood serum, TG was measured by Glycerol-3-phosphate Oxidase-Peoxidase (GPOPAP), TC by Cholesterol Oxidase-Peroxidase (CHOD-PAP), and HDL-C by sedimentation method, LDL-C by Friedwald calculation and IL-6 by ELISA method. The serum values of each parameter were analyzed using one-way ANOVA at P≤0.05. In all experimental groups significant decrease of visceral fat was obvious as compared with control PCOS group. LDL-C, TC and IL-6 levels in experimental groups, particularly at dose of 50 mg/kg of GSE, were significantly decreased as compared with PCOS group. However, HDL-C levels were not significantly changed. According to the findings of this study, it can be concluded that GSE with its effects on serum TC, LDL-C and IL-6 could reduce the effects of dyslipidemia and inflammation in PCOS rats and improve systemic symptoms of PCOS. Copyright© by Royan Institute. All rights reserved.

  10. Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion.

    Science.gov (United States)

    Turner, K; Pflugfelder, S C; Ji, Z; Feuer, W J; Stern, M; Reis, B L

    2000-07-01

    To evaluate interleukin-6 (IL-6) levels in the conjunctival epithelium of patients with moderate to severe dry eye disease before and after treatment with cyclosporin A ophthalmic emulsion (CsA) or its vehicle. Conjunctival cytology specimens were obtained from a subset of patients enrolled in a 6-month randomized, double-masked clinical trial of the efficacy and safety of topical CsA at baseline and after 3 and 6 months of B.I.D. treatment with 0.05% cyclosporine emulsion (n = 13), 0.1% cyclosporine emulsion (n = 8), or vehicle (n = 10). RNA was extracted and a competitive reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the levels of mRNA encoding the inflammatory cytokine IL-6 and a housekeeping gene, G3PDH. Levels of IL-6 and G3PDH were measured and compared. There was no change from baseline in the level of G3PDH after 3 or 6 months in any group. IL-6 normalized for G3PDH (IL-6/G3PDH ratio) was not different from baseline at 3 months but showed a significant decrease from baseline in the group treated with 0.05% CsA (p = 0.048) at 6 months. No significant between-group differences were noted and no correlation was observed between the change in IL-6/G3PDH and corneal fluorescein staining. This preliminary, small-cohort study showed a decrease in IL-6 in the conjunctival epithelium of moderate to severe dry eye patients treated with 0.05% CsA for 6 months. The observed decrease suggests that dry eye disease involves immune-mediated inflammatory processes that may be decreased by treatment with topical ophthalmic cyclosporine.

  11. Lapachol suppresses cell proliferation and secretion of interleukin-6 and plasminogen activator inhibitor-1 of fibroblasts derived from hypertrophic scars.

    Science.gov (United States)

    Matsui, Takuya; Ito, Chihiro; Oda, Makiko; Itoigawa, Masataka; Yokoo, Kazuhisa; Okada, Tadashi; Furukawa, Hiroshi

    2011-07-01

    The pathogenesis and therapy of hypertrophic scar have not yet been established. Our aim was to investigate the antiproliferative and antisecretory effects of lapachol, isolated from the stem bark of Avicennia rumphiana Hall. f., on hypertrophic scar fibroblasts. The effects of lapachol on hypertrophic scar fibroblast proliferation were measured using the MTT assay, cell-cycle analyses and lactate dehydrogenase assays. The type I collagen α-chain (COL1A1), interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) mRNA and/or protein levels of hypertrophic scar-fibroblasts were quantitated by real-time PCR and ELISA. Lapachol at 25 and 50 µm significantly inhibited the in vitro proliferation of hypertrophic scar fibroblasts, but not fibroblasts from non-lesional skin sites. In addition, lapachol had no apparent effect on cell cycle and lactate dehydrogenase activity in conditioned medium from lapachol-treated hypertrophic scar fibroblasts was nearly equal to that in medium from vehicle-treated cells. Lapachol treatment also inhibited COL1A1 and PAI-1 mRNA levels in hypertrophic scar fibroblasts, but did not affect IL-6 mRNA levels. The protein levels of IL-6 and PAI-1 in conditioned medium from hypertrophic scar fibroblasts treated with 50 µm lapachol were lower than those from vehicle-treated hypertrophic scar fibroblasts. Lapachol decreased the proliferation rate of hypertrophic scar fibroblasts. As IL-6 and PAI-1 secretion was also lowered in lapachol-treated hypertrophic scar fibroblasts, our findings suggested that lapachol may have suppressed extracellular matrix hyperplasia in wound healing and possibly alleviated the formation of hypertrophic scar. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  12. Oral L-arginine modulates blood lactate and interleukin-6 after exercise in HIV-infected men.

    Science.gov (United States)

    Alves, G N; Tavares, A M V; Vieira, P J C; Sprinz, E; Ribeiro, J P

    2014-04-01

    The acute administration of L-arginine (L-arg), a nitric oxide (NO) precursor, reduces lactate (LAC) concentration after exercise in healthy individuals. Lower concentration of L-arg may enhance the action of some inflammatory cytokines in HIV-1 infected patients. We tested the hypothesis that acute L-arg administration may reduce post-exercise blood LAC and inflammatory cytokines levels in HIV-infected patients. 10 HIV-infected men performed 2 maximal incremental cardiopulmonary exercise tests, separated by one week. 30 min before each test, patients received oral placebo or 20 g of L-arg, in random order. Blood LAC, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured before and up to 60 min after exercise. L-arg administration had no significant effect on exercise performance. Compared to placebo, L-arg administration reduced maximal post-exercise blood LAC from 8.7±0.6 to 6.9±0.4 mmol.L-1 (p<0.05). L-arg administration had no significant effect on TNF-alpha or IL-10 concentrations, but increased post-exercise IL-6 (placebo=19±3pg.mL-1; L-arg=63±8 pg.mL-1; p<0.05). In HIV-1 infected men, acute administration of L-arg reduces post-exercise blood LAC and increases IL-6 levels, suggesting the activation of the L-arg-NO pathway, with possible anti-inflammatory consequences. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Curcumin suppresses the production of interleukin-6 in Prevotella intermedia lipopolysaccharide-activated RAW 264.7 cells.

    Science.gov (United States)

    Kim, Sung-Jo

    2011-06-01

    Curcumin is known to exert numerous biological effects including anti-inflammatory activity. In this study, we investigated the effects of curcumin on the production of interleukin-6 (IL-6) by murine macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory periodontal disease, and sought to determine the underlying mechanisms of action. LPS was prepared from lyophilized P. intermedia ATCC 25611 cells by the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time polymerase chain reaction to detect IL-6 mRNA expression. IκB-α degradation, nuclear translocation of NF-κB subunits, and STAT1 phosphorylation were characterized via immunoblotting. DNA-binding of NF-κB was also analyzed. Curcumin strongly suppressed the production of IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW 264.7 cells. Curcumin did not inhibit the degradation of IκB-α induced by P. intermedia LPS. Curcumin blocked NF-κB signaling through the inhibition of nuclear translocation of NF-κB p50 subunit. Curcumin also attenuated DNA binding activity of p50 and p65 subunits and suppressed STAT1 phosphorylation. Although further study is required to explore the detailed mechanism of action, curcumin may contribute to blockade of the host-destructive processes mediated by IL-6 and appears to have potential therapeutic values in the treatment of inflammatory periodontal disease.

  14. Calorie restriction dose-dependently abates lipopolysaccharide-induced fever, sickness behavior, and circulating interleukin-6 while increasing corticosterone.

    Science.gov (United States)

    MacDonald, Leah; Hazi, Agnes; Paolini, Antonio G; Kent, Stephen

    2014-08-01

    In mice a 50% calorie restriction (CR) for 28days attenuates sickness behavior after lipopolysaccharide (LPS) and these mice demonstrate a central anti-inflammatory bias. This study examined the dose-dependent effect of CR on sickness behavior (fever, anorexia, cachexia) and peripheral immune markers post-LPS. Male Sprague-Dawley rats fed ad libitum or CR by 50% for 14, 21, or 28days were injected on day 15, 22, or 29 with 50μg/kg of LPS or saline (1mL/500g). Changes in body temperature (Tb), locomotor activity, body weight, and food intake were determined. A separate cohort of rats was fed ad libitum or CR by 50% for 28days and serum levels of corticosterone (CORT), interleukin 6 (IL-6), and IL-10 were determined at 0, 2, and 4h post-LPS. The rats CR for 28days demonstrated the largest attenuation of sickness behavior: no fever, limited reduction in locomotor activity, no anorexia, and reduced cachexia following LPS. Rats CR for 14 and 21days demonstrated a partial attenuation of sickness behavior. Rats CR for 14days demonstrated a larger increase in Tb, larger reduction in locomotor activity, and larger weight loss compared to rats CR for 21days. Serum CORT was increased at 2h post-LPS in ad libitum and CR groups; however it was two times larger in the CR animals. Levels of IL-6 were significantly attenuated at 2h post-LPS in the CR animals. IL-10 levels were similar post-LPS. CR results in an enhanced anti-inflammatory response in the form of increased CORT and diminished pro-inflammatory signals. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. An intradialytic increase in serum interleukin-6 levels is associated with an increased mortality in hemodialysis patients.

    Science.gov (United States)

    Lichtenberg, Shelly; Korzets, Asher; Zingerman, Boris; Green, Hefziba; Erman, Arie; Gafter, Uzi; Rozen-Zvi, Benaya

    2015-05-01

    The inflammatory marker interleukin-6 (IL-6) increases early in the inflammatory cascade. The aim of this study was to evaluate whether an increase in serum IL-6 levels during a hemodialysis (HD) session is associated with mortality. 57 adult patients treated with HD for more than 1 month were prospectively studied over a 3-year follow-up period. Demographic and clinical data were collected and blood samples were drawn before and after a midweek HD session. Events of death and censoring were recorded. During the 3-year follow-up, 50.8% of the patients died. In univariate Cox regression analysis, an increase in IL-6 levels during HD was associated with an increased mortality (HR 1.41 per pg/ml; 95% CI 1.06 to 1.88; P = .017). In multivariate Cox models, the only independent predictors of all-cause mortality were: an increase in IL-6 levels during dialysis (HR 1.46 per pg/ml; 95% CI 1.08 to 1.98; P = .014), higher baseline C-reactive protein (CRP) levels and older age. When predictors of an increase in serum IL-6 levels during HD were introduced into the model, mortality was still significantly associated with IL-6 elevation during dialysis (HR 1.47 per pg/ml, 95% CI 1.01 to 2.14; P = .045). A rise in serum IL-6 levels during a single HD session is associated with a higher mortality among HD patients, independent of predialysis CRP or IL-6 levels. The results may imply the presence of an intradialytic inflammatory response that affects survival in HD patients.

  16. Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3 activation in experimental ulcerative colitis.

    Directory of Open Access Journals (Sweden)

    Min Jeoung Lee

    Full Text Available BACKGROUND: Intestinal epithelium is essential for maintaining normal intestinal homeostasis; its breakdown leads to chronic inflammatory pathologies, such as inflammatory bowel diseases (IBDs. Although high concentrations of S100A9 protein and interleukin-6 (IL-6 are found in patients with IBD, the expression mechanism of S100A9 in colonic epithelial cells (CECs remains elusive. We investigated the role of IL-6 in S100A9 expression in CECs using a colitis model. METHODS: IL-6 and S100A9 expression, signal transducer and activator of transcription 3 (STAT3 phosphorylation, and infiltration of immune cells were analyzed in mice with dextran sulfate sodium (DSS-induced colitis. The effects of soluble gp130-Fc protein (sgp130Fc and S100A9 small interfering (si RNA (si-S100A9 on DSS-induced colitis were evaluated. The molecular mechanism of S100A9 expression was investigated in an IL-6-treated Caco-2 cell line using chromatin immunoprecipitation assays. RESULTS: IL-6 concentrations increased significantly in the colon tissues of DSS-treated mice. sgp130Fc or si-S100A9 administration to DSS-treated mice reduced granulocyte infiltration in CECs and induced the down-regulation of S100A9 and colitis disease activity. Treatment with STAT3 inhibitors upon IL-6 stimulation in the Caco-2 cell line demonstrated that IL-6 mediated S100A9 expression through STAT3 activation. Moreover, we found that phospho-STAT3 binds directly to the S100A9 promoter. S100A9 may recruit immune cells into inflamed colon tissues. CONCLUSIONS: Elevated S100A9 expression in CECs mediated by an IL-6/STAT3 signaling cascade may play an important role in the development of colitis.

  17. Anti-fibrotic Activity and Enhanced Interleukin-6 Production by Hepatic Stellate cells in Response to Imatinib Mesylate

    Science.gov (United States)

    Kim, Youngchul; Fiel, Maria Isabel; Albanis, Efsevia; Chou, Hsin I; Zhang, Weijia; Khitrov, Gregory; Friedman, Scott L.

    2012-01-01

    Objective To examine imatinib mesylate’s effects on stellate cell responses in vivo and in vitro. The hepatic stellate cell (HSC) is a key target of anti-fibrotic therapies. Imatinib mesylate is a small molecule receptor tyrosine kinase (RTK) inhibitors indicated for treatment of chronic myelogenous leukemia and GI stromal tumors. Design Because imatinib inhibits β-PDGFR signaling, which stimulates HSC proliferation, we assessed its activity in culture and in vivo, and examined downstream targets of its activity in a human stellate cell line (LX-2) using cDNA microarray. Methods and Results Imatinib inhibited proliferation of LX-2 cells (0.5 mM – 10 mM) but not primary human stellate cells, with no effect on viability, associated with attenuated β-PDGFR phosphorylation. Mitochondrial activity and superoxide anion production were decreased in response to imatinib. cDNA microarray uncovered up-regulation of 29 genes in response to imatinib, including interleukin-6 (IL-6) mRNA, which was correlated with progressive IL-6 secretion. Imatinib also decreased gene expression of collagen α1(I), alpha SMA, β-PDGFR, TGF β1 receptor type 1, matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2). In vivo, imatinib administered to rats beginning 4 weeks after starting thioacetamide led to reduced collagen content, with significant reductions in portal pressure and down-regulation of fibrogenic genes in whole liver. Importantly, hepatic IL-6 mRNA levels were significantly increased in TAA-treated animals receiving imatinib. Conclusions: These findings reinforce the anti-fibrotic activity of imatinib and uncover an unexpected link between inhibition of HSC activation by imatinib and enhanced secretion of IL-6, a regenerative cytokine. PMID:22507133

  18. Staphylococcus aureus regulates secretion of interleukin-6 and monocyte chemoattractant protein-1 through activation of nuclear factor kappaB signaling pathway in human osteoblasts

    Directory of Open Access Journals (Sweden)

    Rende Ning

    Full Text Available OBJECTIVE: Activation of nuclear factor kappaB by diverse bacteria regulates the secretion of chemokines and cytokines. Staphylococcus aureus (S. aureus-infected osteoblasts can significantly increase the secretion of interleukin-6 and monocyte chemoattractant protein-1. The aim of this study was to investigate whether S. aureus can activate nuclear factor kappaB in human osteoblasts, and whether the activation of nuclear factor kappaB by S. aureus regulates the secretion of interleukin-6 and monocyte chemoattractant protein-1. METHODS: Immunoblot and electrophoretic mobility shift assay were used to detect the degradation of IκBa and activation of nuclear factor kappaB in human osteoblasts in response to S. aureus, respectively. Enzyme-linked immunosorbent assay was used to measure the secretion of interleukin-6 and monocyte chemoattractant protein-1 in the supernatants. Lastly, carbobenzoxyl-l-leucinyl-l-leucinyl-l-leucinal, an inhibitor of the nuclear factor kappaB, was used to determine if activation of nuclear factor kappaB by S. aureus in human osteoblasts regulates the secretions of interleukin-6 and monocyte chemoattractant protein-1. RESULTS: Our results for the first time demonstrated that S. aureus can induce the degradation of IκBa and activation of nuclear factor kappaB in human osteoblasts in a time and dose-dependent manner. In addition, inhibition of nuclear factor kappaB by carbobenzoxyl-l-leucinyl-l-leucinyl-l-leucinal suppressed the secretion of interleukin-6 and monocyte chemoattractant protein-1 in the supernatants of S. aureus-infected human osteoblasts in a dose-dependent manner. CONCLUSION: These findings suggest that S. aureus can activate nuclear factor kappaB in human osteoblasts, and subsequently regulate the secretion of interleukin-6 and monocyte chemoattractant protein-1. The nuclear factor kappaB transcription factor regulates a number of genes involved in a wide variety of biological processes. Further study of

  19. Interleukin-6 expression on inflamed rat dental pulp tissue after capped with Trigona sp. propolis from south Sulawesi, Indonesia

    Directory of Open Access Journals (Sweden)

    Ardo Sabir

    2017-07-01

    Full Text Available Background: Propolis is a natural product of plant resins collected by honeybees from various plant sources. It is used as a remedy in folk medicine since ancient times because of its several biological and pharmacological properties. Recently, propolis has been used by dentist to treat various oral diseases. It was always mentioned as an anti-inflammatory agent. Cytokines are proteins that provide communication between cells and play a critical role in a wide variety of processes. It released from cells in an inflammatory process that active, mediate or potential actions of other cells or tissues. When dental pulp has inflammation, several pro-inflammatory cytokines including Interleukin-6 (IL-6 was released by innate immune cells. Objective: To analyse the expression of IL-6 on inflamed rat dental pulp tissue following application of propolis. Material and methods: Trigona sp. propolis was obtained from Luwu Regency, south Sulawesi Province, Indonesia. Flavonoid and non-flavonoid extracts were purified from propolis using thin layer chromatography. The study was applied on 80 male Sprague Dawley rats, 10–12 weeks of age, divided randomly and equally into 5 groups. Group I, as negative control group was not conducted any treatment. At group II, III, IV and V. A Class I cavity (Black Classification were made on the occlusal surface of right maxillary first molar. The dental pulp was perforated using dental explorer and allowed in the oral environment for 1 h, after that, Ethanolic Extract Propolis (EEP (Group II, Extract Flavonoid-Propolis (EFP (Group III, Extract Non-Flavonoid Propolis (ENFP (Group IV, or Calcium Hydroxide (Ca(OH2 (Group V were applied on dental pulp. All cavities were then filled with Glass Ionomer Cement as permanent filling. The rats being sacrificed in 6 h, 2 days, 4 days and 7 days. Sample biopsy were obtained, IL-6 expression was detected by using immunohistochemistry method. Data was analyzed statistically using

  20. Interleukin-6 expression on inflamed rat dental pulp tissue after capped withTrigonasp. propolis from south Sulawesi, Indonesia.

    Science.gov (United States)

    Sabir, Ardo; Sumidarti, Andi

    2017-07-01

    Background: Propolis is a natural product of plant resins collected by honeybees from various plant sources. It is used as a remedy in folk medicine since ancient times because of its several biological and pharmacological properties. Recently, propolis has been used by dentist to treat various oral diseases. It was always mentioned as an anti-inflammatory agent. Cytokines are proteins that provide communication between cells and play a critical role in a wide variety of processes. It released from cells in an inflammatory process that active, mediate or potential actions of other cells or tissues. When dental pulp has inflammation, several pro-inflammatory cytokines including Interleukin-6 (IL-6) was released by innate immune cells. Objective: To analyse the expression of IL-6 on inflamed rat dental pulp tissue following application of propolis. Material and methods: Trigona sp. propolis was obtained from Luwu Regency, south Sulawesi Province, Indonesia. Flavonoid and non-flavonoid extracts were purified from propolis using thin layer chromatography. The study was applied on 80 male Sprague Dawley rats, 10-12 weeks of age, divided randomly and equally into 5 groups. Group I, as negative control group was not conducted any treatment. At group II, III, IV and V. A Class I cavity (Black Classification) were made on the occlusal surface of right maxillary first molar. The dental pulp was perforated using dental explorer and allowed in the oral environment for 1 h, after that, Ethanolic Extract Propolis (EEP) (Group II), Extract Flavonoid-Propolis (EFP) (Group III), Extract Non-Flavonoid Propolis (ENFP) (Group IV), or Calcium Hydroxide (Ca(OH) 2 ) (Group V) were applied on dental pulp. All cavities were then filled with Glass Ionomer Cement as permanent filling. The rats being sacrificed in 6 h, 2 days, 4 days and 7 days. Sample biopsy were obtained, IL-6 expression was detected by using immunohistochemistry method. Data was analyzed statistically using Freidman

  1. The interaction between coagulation factor 2 receptor and interleukin 6 haplotypes increases the risk of myocardial infarction in men.

    Directory of Open Access Journals (Sweden)

    Bruna Gigante

    Full Text Available The aim of the study was to investigate if the interaction between the coagulation factor 2 receptor (F2R and the interleukin 6 (IL6 haplotypes modulates the risk of myocardial infarction (MI in the Stockholm Heart Epidemiology Program (SHEEP. Seven SNPs at the F2R locus and three SNPs at the IL6 locus were genotyped. Haplotypes and haplotype pairs (IL6*F2R were generated. A logistic regression analysis was performed to analyze the association of the haplotypes and haplotype pairs with the MI risk. Presence of an interaction between the two haplotypes in each haplotype pair was calculated using two different methods: the statistical, on a multiplicative scale, which includes the cross product of the two factors into the logistic regression model; the biological, on an additive scale, which evaluates the relative risk associated with the joint presence of both factors. The ratio between the observed and the predicted effect of the joint exposure, the synergy index (S, indicates the presence of a synergy (S>1 or of an antagonism (S<1. None of the haplotypes within the two loci was associated with the risk of MI. Out of 22 different haplotype pairs, the haplotype pair 17 GGG*ADGTCCT was associated with an increased risk of MI with an OR (95%CI of 1.58 (1.05-2.41 (p = 0.02 in the crude and an OR of 1.72 (1.11-2.67 (p = 0.01 in the adjusted analysis. We observed the presence of an interaction on a multiplicative scale with an OR (95%CI of 2.24 (1.27-3.95 (p = 0.005 and a slight interactive effect between the two haplotypes on an additive scale with an OR (95%CI of 1.56 (1.02-2.37 (p = 0.03 and S of 1.66 (0.89-31. In conclusion, our results support the hypothesis that the interaction between these two functionally related genes may influence the risk of MI and suggest new mechanisms involved in the genetic susceptibility to MI.

  2. Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α

    Directory of Open Access Journals (Sweden)

    Toledo JO

    2015-01-01

    Full Text Available Juliana O Toledo,1 Clayton F Moraes,2,3 Vinícius C Souza,2 Audrey C Tonet-Furioso,2 Luís CC Afonso,4 Cláudio Córdova,3 Otávio T Nóbrega1,2 1Graduate Program in Health Sciences, 2Graduate Program in Medical Sciences, University of Brasília, Brasília, 3Graduate Program in Gerontology, Catholic University of Brasília, Brasília, 4Research Center in Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil Objective: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ] in response to multivariate drug directions for blood pressure (BP control.Methods: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention.Results: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P<0.01 at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin–angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group.Conclusion: Our data demonstrates that a clinically guided antihypertensive treatment is effective in

  3. Muscle strength but not functional capacity is associated with plasma interleukin-6 levels of community-dwelling elderly women

    Directory of Open Access Journals (Sweden)

    D.M.G. Oliveira

    2008-12-01

    Full Text Available The association of plasma interleukin-6 (IL-6 levels, muscle strength and functional capacity was investigated in a cross-sectional study of community-dwelling elderly women from Belo Horizonte, Brazil. Elderly people who present controlled chronic diseases with no negative impact on physical, psychosocial and mental functionality are considered to be community-dwelling. Psychological and social stress due to unsuccessfully aging can represent a risk for immune system disfunctions. IL-6 levels, isokinetic muscle strength of knee flexion/extension, and functional tests to determine time required to rise from a chair and gait velocity were measured in 57 participants (71.21 ± 7.38 years. Serum levels of IL-6 were measured in duplicate and were performed within one single assay (mouse monoclonal antibody against IL-6; High-Sensitivity, Quantikine®, R & D Systems, USA; intra-assay coefficient of variance = 6.9-7.4%; interassay coefficient of variance = 9.6-6.5%; sensitivity = 0.016-0.110 pg/mL; mean = 0.039 pg/mL. Muscle strength was assessed with the isokinetic dynamometer Biodex System 3 Pro®. After the Shapiro-Wilk normality test was applied, correlations were investigated using Spearman and Kruskal-Wallis tests. Post hoc analysis was performed using the Dunn test. A significant negative correlation was observed between plasma IL-6 levels (1.95 ± 1.77 pg/mL and muscle strength for knee flexion (70.70 ± 21.14%; r = -0.265; P = 0.047 and extension (271.84 ± 67.85%; r = -0.315; P = 0.017. No significant correlation was observed between IL-6 levels and the functional tests (time to rise from a chair = 14.65 ± 2.82 s and gait velocity = 0.95 ± 0.14 m/s. These results suggest that IL-6 is associated with reduced muscle strength.

  4. Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Li-Wen [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hsieh, Bau-Shan; Cheng, Hsiao-Ling [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hu, Yu-Chen [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Chang, Wen-Tsan [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Division of Hepatobiliarypancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan (China); Chang, Kee-Lung, E-mail: Chang.KeeLung@msa.hinet.net [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2012-01-15

    Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100 μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24 h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Highlights: ► Arecoline has potential to prevent against basal cell carcinoma tumorigenesis. ► It has more effectiveness on BCC as compared with a human keratinocyte cell line. ► Mechanisms involved including reducing tumor cells’ survival factor IL-6, ► Decreasing Cdc25C phosphatase, enhancing tumor suppressor factor p53, ► Eliciting G2/M

  5. Association of interleukin-6 signalling with the muscle stem cell response following muscle-lengthening contractions in humans.

    Directory of Open Access Journals (Sweden)

    Bryon R McKay

    Full Text Available BACKGROUND: The regulation of muscle stem cells in humans in response to muscle injury remains largely undefined. Recently, interleukin-6 (IL-6 has been implicated in muscle stem cell (satellite cell-mediated muscle hypertrophy in animals; however, the role of IL-6 in the satellite cell (SC response following muscle-lengthening contractions in humans has not been studied. METHODOLOGY/PRINCIPAL FINDINGS: Eight subjects (age 22+/-1 y; 79+/-8 kg performed 300 maximal unilateral lengthening contractions (3.14 rad.s(-1 of the knee extensors. Blood and muscle samples were collected before and at 4, 24, 72, and 120 hours post intervention. IL-6, IL-6 receptor, IL-6R(alpha, cyclin D1, suppressor of cytokine signling-3 (SOCS3 mRNA were measured using quantitative RT-PCR and serum IL-6 protein was measured using an ELISA kit. JAK2 and STAT3 phosphorylated and total protein was measured using western blotting techniques. Immunohistochemical analysis of muscle cross-sections was performed for the quantification of SCs (Pax7(+ cells as well as the expression of phosphorylated STAT3, IL-6, IL-6R(alpha, and PCNA across all time-points. The SC response, as defined by an amplification of Pax7(+ cells, was rapid, increasing by 24 h and peaking 72 h following the intervention. Muscle IL-6 mRNA increased following the intervention, which correlated strongly (R(2 = 0.89, p<0.002 with an increase in serum IL-6 concentration. SC IL-6R(alpha protein was expressed on the fiber, but was also localized to the SC, and IL-6(+ SC increased rapidly following muscle-lengthening contractions and returned to basal levels by 72 h post-intervention, demonstrating an acute temporal expression of IL-6 with SC. Phosphorylated STAT3 was evident in SCs 4 h after lengthening contraction, and the downstream genes, cyclin D1 and SOCS3 were significantly elevated 24 hours after the intervention. CONCLUSIONS/SIGNIFICANCE: The increased expression of STAT3 responsive genes and expression of

  6. Preexercise energy drink consumption does not improve endurance cycling performance but increases lactate, monocyte, and interleukin-6 response.

    Science.gov (United States)

    Phillips, Melody D; Rola, Kelyn S; Christensen, Kenneth V; Ross, Jacob W; Mitchell, Joel B

    2014-05-01

    The purpose of this study was to investigate the influence of an energy drink (ED) on cycling performance and immune-related variables. Eleven trained male cyclists (33.4 ± 8.9 years; 81 ± 7.6 kg; maximal VO2, 52 ± 3.4 ml·kg(-1)·min(-1)) consumed 500 ml of (a) ED (2.0 g taurine, 1.2 g glucuronolactone, 160 mg caffeine, 56 g carbohydrate [CHO], and B vitamins), (b) cola matched for caffeine and CHO (CC), or (c) flavored placebo (PL: sparking water and flavoring) 50 minutes before racing in a randomized, crossover design. Performance was measured as time to complete (TTC) a 25-mile simulated road race. Blood was collected at baseline, 30 minutes after drink consumption, during exercise at miles 5 (M5), 15 (M15), and immediately (POEX) and 30 minutes (30minPO) after exercise. TTC was not different (p > 0.05) among trials (ED, 68.6 ± 2.7; CC, 68.9 ± 3.8; PL, 69.6 ± 3.8 minutes). Consumption of CC and ED elicited a mild hypoglycemia elicited a mild hypoglycemia during cycling. POEX interleukin-6 (IL-6) was greatest after ED, whereas CC IL-6 was greater than PL (10.2 ± 1.6, 6.7 ± 0.6, and 4.8 ± 0.7 pg·ml(-1), respectively; p Cycling increased leukocyte number in all conditions with ED leukocyte number greater than that of PL at M15 (9.8 ± 0.6, 8.5 ± 0.3 × 10(6) cells·mL(-1)). Energy drink induced an earlier recruitment of monocytes to the blood stream than CC. Mean fat oxidation was greater in PL compared with CC (0.43 ± 0.06 and 0.28 ± 0.04 g·min(-1); p = 0.033) but did not differ between ED (0.32 ± 0.06) and PL. Lactate was higher in ED compared with CC and PL at M5 and M15 (p = 0.003), but there was no significant influence of either ED or CC on performance. Carbohydrate and caffeine consumption before endurance cycling significantly increased the IL-6 release and leukocytosis, and the additional ingredients in ED seem to have further augmented these responses.

  7. Effects of the interleukin-6 (IL-6) polymorphism on toxic metal and trace element levels in placental tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kayaalti, Zeliha, E-mail: kayaalti@medicine.ankara.edu.tr [Ankara University, Institute of Forensic Sciences, Dikimevi, 06590, Ankara (Turkey); Tekin, Deniz; Aliyev, Vugar [Ankara University, Institute of Forensic Sciences, Dikimevi, 06590, Ankara (Turkey); Yalcin, Serap [Ahi Evran University, Kirsehir (Turkey); Kurtay, Guelay [Ankara University, Faculty of Medicine, Department of Obstetrics and Gynecology, Dikimevi, 06590, Ankara (Turkey); Soeylemezoglu, Tuelin [Ankara University, Institute of Forensic Sciences, Dikimevi, 06590, Ankara (Turkey)

    2011-11-01

    The placenta is a crucial organ of fetal origin that functions in providing nutrients to the fetus from the mother. During pregnancy, the need for essential micronutrients, such as Fe and Zn, increases due to the requirements of the growing fetus. Maternal Fe deficiency induces an increase in Cu levels and can also affect cytokine levels in the placenta. On the other hand, Cu deficiency, although not as common, can also have destructive effects on the fetus. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities, including such as immune responses, acute-phase reactions, and inflammation. The placenta produces a significant amount of IL-6 during pregnancy. The effects of the IL-6 -174 G/C single nucleotide polymorphism (SNP) on IL-6 gene transcription and on plasma cytokine levels were assessed in the present study. We investigated the association between the IL-6 -174 G/C polymorphism and trace element/toxic metal levels in placental tissues. For the purposes of this study, 95 healthy volunteers were evaluated. Presence of the IL-6 polymorphism was determined using the standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique, and metal levels were analyzed by atomic absorption spectrometry (AAS). Based on our data, there were no significant associations between the IL-6 -174 G/C polymorphism and Pb, Cd, Fe, or Zn levels in the placental tissues (p > 0.05), but a statistically significant association was detected between the polymorphism and Cu levels (p = 0.016). We determined that the mean Cu levels in the placental tissues from individuals with GG, GC and CC genotypes were 5.62 {+-} 1.98, 6.22 {+-} 3.22 and 8.00 {+-} 1.32 ppm, respectively, whereas the overall mean Cu level from the placental tissues was 5.98 {+-} 2.51 ppm. - Highlights: {yields} We studied between the association of IL-6 polymorphism and metal levels in the placenta tissues. {yields} It was the first report evaluating

  8. The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

    DEFF Research Database (Denmark)

    Kolsum, Umme; Roy, Kay; Starkey, Cerys

    2009-01-01

    BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...

  9. The repeatability of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein in COPD patients over one year

    DEFF Research Database (Denmark)

    Kolsum, Umme; Roy, Kay; Starkey, Cerys

    2009-01-01

    BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...

  10. The short-term effects of non-surgical periodontal therapy on the circulating levels of interleukin-6 and C-reactive protein in patients with chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Annie Kitty George

    2013-01-01

    Full Text Available Background: Recent epidemiological studies have shown that periodontal infection is a risk factor for a number of systemic diseases and conditions. In addition to the conventional risk factors, chronic infection and the subsequent generation of a systemic inflammatory response may be associated with this increased risk. Aims: This study was conducted to determine whether the presence of chronic periodontitis and subsequent non-surgical periodontal therapy could influence the serum levels of interleukin-6 and C-reactive protein (CRP in patients with severe chronic generalized periodontitis. Settings and Design: Participants were selected from subjects who attended the Department of Periodontics and Oral Implantololgy, Government Dental College, Thiruvananthapuram. Materials and Methods: Sera were obtained from 25 patients with periodontitis for baseline examination and reassessment after completion of treatment. As a control, sera were also obtained from 20 subjects without periodontitis. Interleukin-6 was determined by sensitive enzyme-linked immunosorbent assay, and high-sensitivity CRP (hsCRP was measured using latex turbidometric immunoassay. Statistical Analysis: Data were analyzed using computer software, Statistical Package for Social Sciences (SPSS version 10. Results: The level of interleukin-6 and hsCRP in the sera of periodontitis patients was seen to be higher than those of healthy controls. Interleukin-6 level tended to decrease with improvement of the periodontal condition following treatment and approached that of control subjects, and this decline was statistically significant. The hsCRP levels also showed a decreasing trend following periodontal treatment. Conclusions: In this study, we were able to show that periodontal disease significantly affects the serum levels of systemic inflammatory markers and that non-surgical periodontal therapy could bring about a decrease in the levels of these inflammatory markers.

  11. Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer

    International Nuclear Information System (INIS)

    Kwon, Kyung A; Roh, Mee Sook; Kim, Hyo-Jin; Kwon, Hyuk-Chan; Lee, Jong Hoon; Kim, Sung Hyun; Oh, Sung Yong; Lee, Suee; Han, Jin-Yeong; Kim, Kyeong Hee; Goh, Ri Young; Choi, Hong Jo; Park, Ki Jae

    2010-01-01

    Angiogenesis is a multistep process in which many growth factors and cytokines have an essential role. Vascular endothelial growth factor (VEGF) is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells through specific cell surface receptors. The interleukin-6 (IL-6) pathway is another mechanism linking angiogenesis to malignancy. C-reactive protein (CRP), a representative marker for inflammation, is known for its association with disease progression in many cancer types. The aim of this study was to determine preoperative serum levels of VEGF, IL-6, and CRP in colorectal carcinoma, and to correlate them with disease status and prognosis. A 132 of 143 patients who underwent curative resection for colorectal cancer were enrolled in this study. 11 patients with resection margin positive were excluded. Factors considered in analysis of the relationship between VEGF, IL-6, and CRP and histological findings. Patient prognosis was investigated. Serum levels of VEGF and IL-6 were assessed using Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured using immunoturbidimetry. Median follow-up duration was 18.53 months (range 0.73-43.17 months) and median age of the patients was 62 years (range, 26-83 years). Mean and median levels of VEGF and CRP in colorectal cancer were significantly higher than in the normal control group; 608 vs. 334 pg/mL and 528 (range 122-3242) vs. 312 (range 16-1121) (p < 0.001); 1.05 mg/dL vs. 0.43 mg/dL and 0.22 (range 0.00-18.40) vs. 0.07 (range 0.02-6.94) (p = 0.002), respectively. However mean and median level of IL-6 in patients were not significantly higher than in control; 14.33 pg/mL vs. 5.65 pg/mL and 6.00 (range 1.02-139.17) vs. 5.30 (4.50-13.78) (p = 0.327). Although IL-6 and CRP levels were not correlated with other pathological findings, VEGF level was significantly correlated with tumor size (p = 0.012) and CEA (p = 0.038). When we established the cutoff value for VEGF (825 pg/mL), IL-6 (8

  12. Young women post-MI have higher plasma concentrations of interleukin-6 before and after stress testing.

    Science.gov (United States)

    Rooks, Cherie R; Ibeanu, Ijeoma; Shah, Amit; Pimple, Pratik; Murrah, Nancy; Shallenberger, Lucy; Pace, Thaddeus; Douglas Bremner, J; Raggi, Paolo; Vaccarino, Viola

    2016-01-01

    Young women have poorer prognosis after myocardial infarction (MI) and a higher rate of mental stress-induced ischemia compared with similarly aged men. A higher inflammatory status may help explain these sex differences. We examined 98 patients (49 women and 49 men) age 18-59years with recent MI (past 6months). Women and men were matched for age, type of MI, and time since MI. Interleukin 6 (IL-6) concentrations were measured at baseline, after mental stress using a speech task, and after exercise/pharmacologic stress (60 and 90min). Depressive symptoms were measured with the Beck Depression Inventory (BDI-II) and angiographic coronary artery disease (CAD) severity was quantified with the Gensini score. Single-photon emission computed tomography (SPECT) was used to obtain a computerized measurement of stress-induced ischemia (summed difference score, or SDS) and determine whether severity of stress-induced ischemia affects the inflammatory response to stress. Analysis was stratified by the median age of 50. Geometric mean concentrations of IL-6 were obtained from general linear regression models. In both age groups, women had less angiographic CAD and a similar level of conventional risk factors compared with men. Despite this, baseline IL-6 geometric means before both mental and physical stress were twice as high in women ⩽50years of age compared to age-matched men (3.8 vs. 1.8pg/mL, p=0.001, across both conditions), while they were similar in women and men age >50years (2.3 vs. 2.2pg/mL, p=0.83). After mental stress, IL-6 concentrations increased in both women and men in a similar fashion and remained twice as high in women ⩽50years than men at both 60min (5.4 vs. 2.6pg/mL, p=0.002) and 90min (5.9 vs. 3.4pg/mL, p=0.01). No significant difference was found between women and men >50years of age at any time point after mental stress. Results were similar for physical stress. After accounting for SDS, IL-6 concentrations in young women remained higher after both

  13. Single intradiscal injection of the interleukin-6 receptor antibody tocilizumab provides short-term relief of discogenic low back pain; prospective comparative cohort study.

    Science.gov (United States)

    Sainoh, Takeshi; Orita, Sumihisa; Miyagi, Masayuki; Inoue, Gen; Yamauchi, Kazuyo; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Inage, Kazuhide; Sato, Jun; Nakata, Yukio; Aoki, Yasuchika; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-01-01

    Inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, are gaining attention as important etiologic factors associated with discogenic low back pain. We conducted a prospective cohort study to evaluate the efficacy and safety of intradiscal injection of the interleukin-6 receptor antibody tocilizumab in patients with discogenic low back pain. Thirty-two consecutive patients were intradiscally injected with 2 mL of 0.5% bupivacaine (control group). Another 31 consecutive patients were intradiscally injected with 40 mg tocilizumab and 1-2 mL of 0.5% bupivacaine (tocilizumab group) at the same time. Prior to treatment, the vertebral origin of low back pain was confirmed in all patients based on pain provocation during discography and pain relief with 1 mL of 1% xylocaine. Numeric rating scale and Oswestry disability index scores were used to evaluate pain level before and after treatment between the 2 groups. The association between pain relief with tocilizumab and intervertebral disc degeneration grade was also determined. At the end of the study (8 weeks after treatment), 30 patients in each group were evaluable. In the tocilizumab group, numeric rating scale and Oswestry disability index scores improved significantly at 2 and 4 weeks after treatment, respectively. Intervertebral disc degeneration was not associated with improvement of numeric rating scale score in the tocilizumab group. Local infection (i.e., discitis) was observed in 1 patient in the tocilizumab group. The results demonstrate the clinical relevance of interleukin-6 in discogenic low back pain. Intradiscal tocilizumab injection was shown to exert a short-term analgesic effect in patients with discogenic low back pain. Further research is required to determine the long-term effects of intradiscal tocilizumab therapy in patients with discogenic low back pain. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  14. Interleukin-6 and granulocyte macrophage-csf in the cerebrospinal fluid from hiv infected subjects with involvement of the central nervous system

    Directory of Open Access Journals (Sweden)

    O. Perrella

    1992-06-01

    Full Text Available We detected the cytokines interleukin-6 (IL-6 and granulocyte macrophage-CSF (GM-CSF by ELISA in the CSF and serum of 30 HIV-infected patients classified as AIDS dementia complex (ADC, and 20 subjects with other neurological diseases (OND. We have found a high incidence of detectable IL-6 and GM-CSF in the CSF of ADC patients compared with OND patients. No statistical differences were observed between both groups for serum IL-6 and GM-CSF levels. These results suggest an intrathecal synthesis of these cytokines and a possible involvement in the pathogenesis of ADC.

  15. Low plasma selenium concentrations, high plasma human immunodeficiency virus load and high interleukin-6 concentrations are risk factors associated with anemia in adults presenting with pulmonary tuberculosis in Zomba district, Malawi

    NARCIS (Netherlands)

    Lettow, van M.; West, C.E.; Meer, van der J.W.M.; Wieringa, F.T.; Semba, R.D.

    2005-01-01

    Although anemia is common among adults with pulmonary tuberculosis and human immunodeficiency virus (HIV) infection in sub-Saharan Africa, the factors contributing to its pathogenesis have not been well characterized. Objective: To characterize the antioxidant micronutrient status, interleukin-6

  16. Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat

    DEFF Research Database (Denmark)

    Hidalgo, Juan; Florit, Sergi; Giralt, Mercedes

    2010-01-01

    Interleukin-6 (IL-6) is a major cytokine involved in both normal physiological brain functions and underlying significant neuropathology. IL-6 has been suggested to play a role in the control of body weight but the results are somewhat controversial. In this study we have challenged transgenic mice...... of increased sympathetic tone. The high-fat diet-induced impaired responses to an insulin tolerance test (ITT), and to an oral glucose tolerance test (OGTT) in both genotypes. The GFAP-IL6 mice did not differ from littermate wild-type (WT) mice in ITT, but they were more glucose intolerant following the high......-fat diet feeding. In summary, the present results demonstrate that brain-specific IL-6 controls body weight which may be a significant factor in physiological conditions and/or in diseases causing neuroinflammation....

  17. Analysis of Ambient Influences Affecting Interleukin-6 Secretion in the Context of Clinical Trials of Stem Cell Therapy for Myocardial Infarction.

    Science.gov (United States)

    Edlinger, Christoph; Wernly, Bernhard; Leisch, Michael; Kammler, Jürgen; Kypta, Alexander; Eder, Sarah; Jung, Christian; Hoppe, Uta C; Lichtenauer, Michael

    2016-01-01

    Contradictory results of large clinical trials of stem cell therapy in acute myocardial infarction (AMI) have impeded a wider clinical use. As signalling via paracrine factors in AMI has received more and more attention recently, we sought to compare processing protocols with special emphasis on interleukin-6 (IL-6), a factor of major relevance for triggering cardioprotective signals via STAT3 and PI3K. Bone marrow and peripheral blood mononuclear cells were processed according to protocols used in the REPAIR-AMI and ASTAMI study. Keeping cells at higher temperatures significantly boosted secretion of IL-6. Moreover, the use of autologous serum and X-Vivo medium was superior over reagents used in the protocol of the ASTAMI study. External influencing factors (higher temperature, use of a modern cell culture medium supplemented with serum) led to higher concentrations of IL-6. These results could provide an explanation for the superior results found in the REPAIR-AMI study.

  18. Rapid communication: acute exposure to mercury from dental amalgam does not affect the levels of C-reactive protein or interleukin-6 in peripheral blood.

    Science.gov (United States)

    Sandborgh-Englund, Gunilla; af Geijersstam, Eric; Loftenius, Annika

    2003-03-28

    In a previous study, a significant increase in serum interleukin-6 (IL-6) was apparent after an acute low-level mercury (Hg) exposure, achieved by removal of amalgam fillings (Loftenius et al., 1998). In the present study, 11 healthy volunteers were exposed to an oral dose of 1 g of pulverized amalgam powder. Hg, IL-6, and C-reactive protein (CRP) levels in plasma were followed before and up to 72 h after exposure. The Hg levels were low and stable prior to exposure and increased rapidly after exposure. The median Hg increase was 12.9 nmol/L, which is considerably higher than in the previous study. No significant change over time was observed for IL-6 and CRP levels. Therefore, it cannot be ruled out that our previous finding of increasing IL-6 levels detected after acute low-level Hg exposure through removal of amalgam fillings was due to the dental treatment per se.

  19. Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; O'Connor, Jemma L; Phillips, Andrew N

    2016-01-01

    BACKGROUND: Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels are linked to adverse outcomes in human immunodeficiency virus (HIV) infection, but the strength of their associations with different clinical end points warrants investigation. METHODS: Participants...... receiving standard of care in 2 HIV trials with measured biomarker levels were followed to ascertain all-cause death, non-AIDS-related death, AIDS, cardiovascular disease (CVD), and non-AIDS-defining malignancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) of each end point for quartiles and log......-dimer (P = .20) as a predictor for different end points. CONCLUSIONS: IL-6 is a stronger predictor of fatal events than of CVD and non-AIDS-defining malignancies. Adjuvant antiinflammatory and antithrombotic therapies should be tested in HIV-infected individuals....

  20. The Interaction of Obstructive Sleep Apnea and Obesity on the Inflammatory Markers C-Reactive Protein and Interleukin-6: The Icelandic Sleep Apnea Cohort

    Science.gov (United States)

    Arnardottir, Erna S.; Maislin, Greg; Schwab, Richard J.; Staley, Bethany; Benediktsdottir, Bryndis; Olafsson, Isleifur; Juliusson, Sigurdur; Romer, Micah; Gislason, Thorarinn; Pack, Allan I.

    2012-01-01

    Study Objectives: To assess the relative roles and interaction of obstructive sleep apnea (OSA) severity and obesity on interleukin-6 (IL-6) and C-reactive protein (CRP) levels. Design: Cross-sectional cohort. Setting: The Icelandic Sleep Apnea Cohort. Participants: 454 untreated OSA patients (380 males and 74 females), mean ± standard deviation age 54.4 ± 10.6 yr. Interventions: N/A. Measurements and Results: Participants underwent a sleep study, abdominal magnetic resonance imaging to measure total abdominal and visceral fat volume, and had fasting morning IL-6 and CRP levels measured in serum. A significantly higher correlation was found for BMI than visceral fat volume with CRP and IL-6 levels. Oxygen desaturation index, hypoxia time, and minimum oxygen saturation (SaO2) significantly correlated with IL-6 and CRP levels, but apnea-hypopnea index did not. When stratified by body mass index (BMI) category, OSA severity was associated with IL-6 levels in obese participants only (BMI > 30 kg/m2). A multiple linear regression model with interaction terms showed an independent association of OSA severity with IL-6 levels and an interaction between OSA severity and BMI, i.e., degree of obesity altered the relationship between OSA and IL-6 levels. An independent association of OSA severity with CRP levels was found for minimum SaO2 only. A similar interaction of OSA severity and BMI on CRP levels was found for males and postmenopausal women. Conclusions: OSA severity is an independent predictor of levels of IL-6 and CRP but interacts with obesity such that this association is found only in obese patients. Citation: Arnardottir ES; Maislin G; Schwab RJ; Staley B; Benediktsdottir B; Olafsson I; Juliusson S; Romer M; Gislason T; Pack AI. The interaction of obstructive sleep apnea and obesity on the inflammatory markers c-reactive protein and interleukin-6: the Icelandic Sleep Apnea Cohort. SLEEP 2012;35(7):921-932. PMID:22754038

  1. Effects of concurrent training on interleukin-6, tumour necrosis factor-alpha and C-reactive protein in middle-aged men.

    Science.gov (United States)

    Libardi, Cleiton Augusto; Souza, Giovana Verginia; Gáspari, Arthur Fernandes; Dos Santos, Claudinei Ferreira; Leite, Sabrina Toffoli; Dias, Rodrigo; Frollini, Anelena B; Brunelli, Diego Trevisan; Cavaglieri, Claudia Regina; Madruga, Vera Aparecida; Chacon-Mikahil, Mara P T

    2011-11-01

    The purpose of this study was to evaluate the effects of moderate- to high-intensity resistance and concurrent training on inflammatory biomarkers and functional capacity in sedentary middle-aged healthy men. Participants were selected on a random basis for resistance training (n = 12), concurrent training (n = 11) and a control group (n = 13). They performed three weekly sessions for 16 weeks (resistance training: 10 exercises with 3 × 8-10 repetition maximum; concurrent training: 6 exercises with 3 × 8-10 repetition maximum, followed by 30 minutes of walking or running at 55-85% [Vdot]O(2peak)). Maximal strength was tested in bench press and leg press. The peak oxygen uptake ([Vdot]O(2peak)) was measured by an incremental exercise test. Tumour necrosis factor-α, interleukin-6 and C-reactive protein were determined. The upper- and lower-body maximal strength increase for both resistance (+42.52%; +20.9%, respectively) and concurrent training (+28.35%; +21.5%, respectively) groups (P = 0.0001).[Vdot]O(2peak) increased in concurrent training when comparing pre- and post-training (P = 0.0001; +15.6%). No differences were found in tumour necrosis factor-α and interleukin-6 for both groups after the exercise. C-reactive protein increased in resistance training (P = 0.004). These findings demonstrated that 16 weeks of moderate- to high-intensity training could improve functional capacity, but did not decrease inflammatory biomarkers in middle-aged men.

  2. The repeatability of interleukin-6, tumor necrosis factor-α, and C-reactive protein in COPD patients over one year

    Directory of Open Access Journals (Sweden)

    Umme Kolsum

    2009-04-01

    Full Text Available Umme Kolsum, Kay Roy, Cerys Starkey, Zoë Borrill, Nick Truman, Jørgen Vestbo, Dave SinghNorth West Lung Research Centre, University of Manchester, South Manchester University Hospitals Trust, Wythenshawe, Manchester, UKBackground: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and C-reactive protein (CRP over one year and examined the relationships between these systemic markers in COPD.Methods: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-α were measured. Repeatability was expressed by intraclass correlation coefficient (Ri and the Bland–Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits.Results: There was moderate repeatability with a very high degree of statistical significance (p ≤ 0.001 between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-α. CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively. There were no other significant associations between the systemic markers at either of the visits.Conclusions: Systemic inflammatory biomarkers IL-6, CRP, and TNF-α were moderately repeatable over a twelve month period in COPD patients. We have also shown that a robust and repeatable association between IL-6 and CRP exists.Keywords: interleukin-6, tumor necrosis factor-α, C-reactive protein, repeatability, COPD   

  3. The relationship of Interleukin-6 -174 G>C gene polymorphism in type 2 diabetic patients with and without diabetic foot ulcers in Turkish population.

    Science.gov (United States)

    Erdogan, Mehmet; Kulaksizoglu, Mustafa; Solmaz, Soner; Berdeli, Afig

    2017-03-01

    We aims investigate Turkish type 2 diabetic patients with/without diabetic foot ulcers and healthy group and examined the contribution of Interleukin (IL)-6 -174 G>C gene polymorphism to the development of diabetic foot ulcers. The Interleukin (IL)-6 -174 G>C genotypes were determined prospectively in 50 patients with diabetic foot ulcers and 35 without diabetic foot ulcers and a control group of 119 healthy individuals. Genotyping of the Interleukin (IL)-6 -174 G>C gene polymorphisms for all individuals was performed by PCR-RFLP method. The genotype IL6 distribution did differ between the control group (CC 13.3%, GC 66.7%, GG 20%) and type 2 diabetic patients (CC 2.4%, GC 47.1%, GG 50.6%) (Pdiabetic patients group (CC 0%, GC 45.7%, GG 54.3%) and diabetic foot ulcers (CC 4%, GC 48%, 48%) (P>0.05). The frequency of the polymorphic G allele in between the control group and type 2 diabetic patients was no similar for the groups (58.4% and 74.1%, respectively) (pdiabetic patients and diabetic foot ulcers was similar for the groups (77.1% and 72%, respectively) (p>0.05). The gene polymorphism of Interleukin-6 -174 G>C and G allele are an risk factor for diabetes, but gene polymorphism of Interleukin-6 -174 G>C is not an independent risk factor for diabetic foot. Genetic factors in the pathogenesis of diabetic foot may also show any changes in different populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Serum biomarker profiles of interleukin-6, tumor necrosis factor alpha, matrix-metalloproteinase-2, and vascular endothelial growth factor in endometriosis staging

    Directory of Open Access Journals (Sweden)

    Wachyu Hadisaputra

    2013-05-01

    Full Text Available Background: The focus of this study was to compare serum biomarkers: interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, matrix-metalloproteinase-2 (MMP-2 and vascular endothelial growth factor (VEGF in endometriosis stage I-II and stage III-IV. Methods: This is a cross-sectional study. Forty endometriosis patients were diagnosed using laparoscopy procedure. Serum sample was taken before the surgery. The serum biomarkers (IL-6, TNF-α, MMP-2, and VEGF were analyzed with ELISA method at the end of research. Mean of serum biomarkers in endometrosis stage I-II and stage III-IV were compared using unpaired t-test. Variables that show significant mean difference were tested using ROC measurement and the optimal cut-off point was determined. Results: There was no significant difference in mean serum biomarkers level of IL-6, TNF-α, and MMP-2 between endometriosis stage I-II and stage III-IV (1.58 ± 0.78 vs 1.55 ± 0.98 pg/mL, 1.5 ± 0.47 vs 1.49 ± 0.29 pg/mL, and 152.04 ± 27.32 vs 140.98 ± 28.08 ng/mL, respectively. On the other hand, the comparison of VEGF level in endometriosis stage I-II and stage III-IV demonstrated significant difference (289.76 ± 188.13 vs 581.29 ± 512.85 pg/mL (p < 0.05. Mean difference of VEGF had AUC of 74.5%. Optimal cut-off point for VEGF was ≥ 314.75 pg/mL with sensitivity 78.6% and specificity 69.2%. Conclusion: This study showed that serum biomarkers of VEGF level (but not IL-6, TNF-α, and MMP-2 can be used to measure the degree of severity in endometriosis. VEGF level of 314.75 pg/mL represents the cut-off point between lower and higher stage of severity. (Med J Indones. 2013;22:76-82Keywords: Endometriosis, interleukin-6, matrix-metalloproteinase-2, TNF-α, vascular endhothelial growth factor

  5. Tumor necrosis factor-alpha and interleukin -6 as diagnostic markers of diabetic complications in children with type I diabetes mellitus

    International Nuclear Information System (INIS)

    El-Nashar, N.A.; Moawad, A.T.; Nassar, E.M.

    2010-01-01

    This study aimed to determine the role of cellular auto immunity and its humoral mediators in pathogenesis and following up of type I diabetes mellitus (TIDM). Therefore, serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), glycemic control, body mass index, duration of the disease and microalbuminuria in children with TIDM were evaluated. This study was conducted on 30 patients suffered from type I diabetes mellitus (TIDM), 14 males and 16 females with mean age of 11.40 ±3.67 years and 20 apparently healthy children served as control (10 male and 10 female). Children with TIDM were classified according to duration: diabetic children for 5 years or less duration (n= 15, duration means: 2.74 ± 1.34 years) and diabetic children > 5 years (n=15, duration means: 7.35 ± 1.49 years); according to glycemic control: children with good glycemic control (n=16, HbAIc: 7.82 ± 2.70) and diabetic children with poor glycemic control (n=14, HbAIc: 10.49 ± 2.72) and according to complication: diabetic children without complications (n= 20) and diabetic children with microvascular or neurological complications (n= 10, nephritic, retinal or neurological complications). Patients and controls were subjected to careful history, clinical examination and laboratory investigations. The following investigations were done for all children; random blood glucose, Glycated hemoglobin (HbAIc %), microalbuminuria and kidney function tests. Serum tumour necrosis factor-alpha (TNF-alpha) and serum interleukin-6 (IL-6) were measured using immuno-enzymometric assay (ELISA). Patients with TIDM with duration more than 5 years, with poor glycemic control and with complications had higher serum glucose levels, higher HbAIc%, higher level of blood urea nitrogen (BUN), serum creatinine, microalbuminuria and elevated serum TNF-alpha (p<0.0001) and IL-6 (p<0.0001) in comparison to the same diabetic patients with 5 years duration or less, with good glycemic control

  6. Serum interleukin-6 levels are increased in HIV-infected patients that develop autoimmune disease during long-term follow-up.

    Science.gov (United States)

    Trovato, M; Ruggeri, R M; Sciacchitano, S; Vicchio, T M; Picerno, I; Pellicanò, G; Valenti, A; Visalli, G

    2018-03-01

    Elevated IL-6 levels have been associated with both autoimmune diseases and treated HIV-seropositive (HIV + ) subjects. However, few data on classic and trans-signaling IL-6 in autoimmune thyroid diseases and HIV + subjects developing autoimmune disorders are currently available. A total of 102 patients were included in the study. They were subdivided into two groups. Group A consisted in 51 HIV + patients, who were followed-up for a period of five years in search of possible occurrence of autoimmune diseases. Ten of them, treated with antiretroviral therapy (ART), developed an autoimmune disorder, namely Hashimoto's thyroiditis, and psoriasis. Group B consisted in 51 patients affected by Hashimoto's thyroiditis (HT). Serum levels of the free form of IL-6 were analyzed by ELISA in all patients and for HIV + patients at the beginning of the follow-up, before initiation of ART. Mean serum levels of IL-6 were similar in Group A and in Group B. In Group B, IL-6 levels showed a 5.8% increase compared with assay minimum detectable dose corresponding to 1% of full serum IL-6 level. However, serum levels of free IL-6 were increased in those HIV + patients who developed autoimmune disorders (5.8±2.8pg/ml) and in these patients, the highest levels of free IL-6 correlated with age and CD4 cellular counts. The present study indicates a correlation between serum free IL-6 levels and the occurrence of autoimmune disease in HIV + population, treated with ART during a long-term follow-up. The increased levels of serum free IL-6 were observed before ART treatment was initiated, indicating that IL-6 measurement in such patients may represent an early predictor of development of autoimmune disease. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. The effects of inspiratory muscle training on plasma interleukin-6 concentration during cycling exercise and a volitional mimic of the exercise hyperpnea.

    Science.gov (United States)

    Mills, Dean E; Johnson, Michael A; McPhilimey, Martin J; Williams, Neil C; Gonzalez, Javier T; Barnett, Yvonne A; Sharpe, Graham R

    2013-10-15

    It is unknown whether the respiratory muscles contribute to exercise-induced increases in plasma interleukin-6 (IL-6) concentration, if this is related to diaphragm fatigue, and whether inspiratory muscle training (IMT) attenuates the plasma IL-6 response to whole body exercise and/or a volitional mimic of the exercise hyperpnea. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1 h of 1) passive rest, 2) cycling exercise at estimated maximal lactate steady state power (EX), and 3) volitional hyperpnea at rest, which mimicked the breathing and respiratory muscle recruitment patterns achieved during EX (HYPEX). Plasma IL-6 concentration remained unchanged during passive rest. The plasma IL-6 response to EX was reduced following IMT (main effect of intervention, P = 0.039) but not PLA (P = 0.272). Plasma IL-6 concentration increased during HYPEX (main effect of time, P muscles contribute to exercise-induced increases in plasma IL-6 concentration in the absence of diaphragm fatigue and that IMT can reduce the magnitude of the response to exercise but not a volitional mimic of the exercise hyperpnea.

  8. Genetic predisposition to higher production of interleukin-6 through -174 G > C polymorphism predicts global cognitive decline in oldest-old with cognitive impairment no dementia

    Directory of Open Access Journals (Sweden)

    Vanessa G. Fraga

    2015-11-01

    Full Text Available Interleukin 6 (IL-6 is a pro-inflammatory cytokine upregulated in neurodegenerative contexts. The polymorphism IL-6 -174 G > C influences release levels of this cytokine. We aimed to evaluate the influence of IL-6 -174 G > C on global cognitive score of a group with cognitive impairment no dementia in one year of follow-up.Methods The subjects were categorized in two groups: short-term decline in global cognitive score and those with short-term stability or improvement. IL-6 174 G > C information were compared among these groups.Results We observed that individuals with cognitive impairment no dementia with GGlowergenotype were more frequent among global cognitive score non-decliners while carriers of at least one Chigherallele were more frequent in the group with global cognitive score decliners (p = 0.012; RR = 3.095 IC95%= 1.087-8.812.Conclusion These results suggest that the higher expression of IL-6 gene may be an independent risk factor for cognitive decline among individuals with cognitive impairment no dementia.

  9. Increased interleukin 6 and tumour necrosis factor α expression in the infrapatellar fat pad of the knee joint with the anterior knee pain syndrome: a preliminary report.

    Science.gov (United States)

    Witoński, Dariusz; Wągrowska-Danilewicz, Małgorzata; Kęska, Rafał; Raczyńska-Witońska, Grażyna; Stasikowska-Kanicka, Olga

    2010-01-01

    The pathway of pain in the anterior knee pain syndrome remains unclear. It has been hypothesized that some biochemical mediators of inflammation, such as cytokines contribute to the process. The objective of this work was to evaluate the synovial membrane and the infrapatellar fat pad expression of the inflammatory mediators and potentially chondrodestructive cytokines interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α) in the anterior knee pain syndrome, and to determine whether the cytokine expression counterpart with/corresponds to the amount of chondral damage in this syndrome. Ten consecutive patients with the anterior knee pain syndrome (group I) participated in the study. Patients with a history of trauma were excluded from this group. For comparison we used 10 patients with anterior cruciate ligament rupture or meniscal lesion with no history of pain in the anterior compartment (group II). Immunohistochemical techniques using a polyclonal rabbit anti-human antibody to IL-6 and a monoclonal mouse anti-human antibody to TNF-α were employed. The results show a statistically significant higher expression of IL-6 in infrapatellar fat pad (p anterior knee pain syndrome could be characterized by infrapatellar fat pad and synovial inflammation variations without the articular cartilage loss.

  10. Tumor Necrosis Factor-α and Interleukin-6: Potential Interorgan Inflammatory Mediators Contributing to Destructive Periodontal Disease in Obesity or Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Roozbeh Khosravi

    2013-01-01

    Full Text Available Obesity has become a worldwide health burden in the last two decades. Obesity has been associated with increased comorbidities, such as coronary artery disease, diabetes, and destructive periodontal disease. Obesity is also part of a group of risk factors occurring together in an individual, which is referred to as metabolic syndrome. Clinical studies have shown higher risk for destructive periodontal disease in obesity and metabolic syndrome. However, the role of obesity and metabolic syndrome in the onset and development of destructive periodontal disease has not yet been fully understood. In this review, we discuss a working model, which focuses on interorgan inflammation as a common etiological factor for destructive periodontal disease associated with obesity and metabolic syndrome. Specifically, we suggest that elevated levels of tumor necrosis factor-α (TNF-α or interleukin 6 (IL-6—both adipokines and known risk factors for destructive periodontal disease—in obesity and metabolic syndrome contribute to the onset and development of destructive periodontal disease. The connections between destructive periodontal disease and systemic conditions, such as obesity or metabolic syndrome, are complex and potentially multidirectional. This review largely focuses on TNF-α and IL-6, inflammatory mediators, as potential common risk factors and does not exclude other biological mechanisms.

  11. A competitive electrochemical immunosensor for the detection of human interleukin-6 based on the electrically heated carbon electrode and silver nanoparticles functionalized labels.

    Science.gov (United States)

    Lou, Yongbing; He, Tingting; Jiang, Fang; Shi, Jian-Jun; Zhu, Jun-Jie

    2014-05-01

    A facile one-step electrochemical reduction method was developed to prepare electrochemically reduced graphene oxide (ERGO) and gold-palladium bimetallic nanoparticles (AuPdNPs) as the platform of immunosensor. A novel competitive electrochemical immunosensor was then proposed by combining the ERGO-AuPdNPs platform with silver nanoparticles (AgNPs) functionalized polystyrene bionanolabel for the sensitive detection of human interleukin-6 (IL-6). An electrically heated carbon electrode (HCPE) was introduced in the detection procedure of the immunosensor, and further improved the sensitivity. The immunosensor exhibited a wide linear response to IL-6 ranging from 0.1 to 100000 pg mL(-1) with a detection limit of 0.059 pg mL(-1). The proposed method showed good precision, broad linear range, acceptable stability and high reproducibility, and could be used for the detection of IL-6 in real samples, which possessed promising application in clinical research. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Interleukin 6 (IL-6) and IL-10 Promoter Region Polymorphisms Are Associated with Risk of Lumbar Disc Herniation in a Northern Chinese Han Population.

    Science.gov (United States)

    Huang, Xiangye; Chen, Feng; Zhao, Jing; Wang, Dezhang; Jing, Shenfeng; Li, Hongmei; Meng, Chunyang

    2017-01-01

    This study assessed the association of single-nucleotide polymorphisms (SNPs) in the proinflammatory cytokines interleukin 6 (IL-6) and IL-10 with the risk of lumbar disc herniation in a Chinese Han population. We collected blood samples from 267 patients with lumbar disc herniation (case group) and 300 normals (control group) and performed analyses of the IL-6 572C/G and 174G/C SNPs as well as the IL-10 592A/C and 1082G/A SNPs using TaqMan technology. The frequencies of the IL-6-572 GG, GC, and CC genotypes were 5.99%, 42.3%, and 51.6%, respectively, in the case group, and 1.6%, 24%, and 64.3%, respectively, in the control group. Thus, the relative risk of the IL-6-572 G genotype (GG plus GC) was 1.69-fold higher for developing lumbar disc herniation compared to the CC genotype (95% confidence interval: 1.16-2.39, p disc herniation (p disc herniation risk in this Northern Chinese Han population.

  13. ASTAXANTHIN MENURUNKAN KADAR VASCULAR ENDOTHELIAL GROWTH FACTOR, TUMOR NECROSIS FACTOR ALPHA, INTERLEUKIN-6, DAN NITRIC OXIDE PADA NONPROLIFERATIVE DIABETIC RETINOPATHY RINGAN: UJI KLINIS TERKENDALI

    Directory of Open Access Journals (Sweden)

    Ni Made Laksmi Utari

    2015-01-01

    Full Text Available Diabetic Retinopathy (DR merupakan komplikasi mikrovaskular pada Diabetes Mellitus (DM dan penyebab kebutaan paling sering pada usia produktif. Hiperglikemia menyebabkan terjadinya reaksiinflamasi dan stres oksidatif  dalam patogenesis DR dipaparkan oleh beberapa peneliti, namun peran antioksidan dalam mengurangi progresifitas DR masih menjadi perdebatan. Penelitian ini bertujuanuntuk mengetahui pemberian astaxanthin 8 mg dapat menurunkan kadar Vascular Endothelial Growth Factor (VEGF, Tumor Necrosis Factor-alpha (TNF-á, Interleukin-6 (IL-6 dan Nitric Oxide (NO padapenderita Non Proliferative Diabetic Retinopathy (NPDR ringan. Penelitian clinical trial dengan perluasan Randomized, Double Blinded, Placebo-Control, Pre and Posttest Group Design ini dilaksanakanpada bulan Juli 2013 - Desember 2013 di Poliklinik Mata RSUP Sanglah Denpasar Bali. Jumlah sampel yang memenuhi kriteria eligibilitas sebanyak 40 pasien NPDR ringan terbagi menjadi 20 pasien  sebagai kelompok perlakuan yang diberikan astaxanthin 8 mg dan 20 pasien NPDR ringan yang diberikan plasebo sebagai kelompok kontrol. Pengambilan sampel darah vena untuk pemeriksaan dilakukan sebelum dan setelah pemberian astaxanthin 8 mg serta plasebo selama 4 minggu. Perbedaan kadar rerata VEGF, TNF-á, IL-6 dan NO dianalisis dengan uji-t jika distribusi data normal dan uji Mann-whitney jika distribusi data tidak  normal. Hasil penelitian ini diharapkan dapat memberikaninformasi mengenai hubungan VEGF, TNF-á, IL-6, dan NO dalam perkembangan NPDR ringan serta manfaat pemberian astaxanthin dalam perkembangan NPDR ringan. [MEDICINA 2014;45:31-37

  14. Evaluation of pretreatment serum interleukin-6 and tumour necrosis factor alpha as a potential biomarker for recurrence in patients with oral squamous cell carcinoma.

    Science.gov (United States)

    Skrinjar, Ivana; Brailo, Vlaho; Vidovic-Juras, Danica; Vucicevic-Boras, Vanja; Milenovic, Aleksandar

    2015-07-01

    Oral squamous cell carcinoma (OSCC) constitutes 3 percent of all cancers with predominant occurrence in middle aged and elderly males. Tumour recurrence worsens disease prognosis and decreases quality of life in patients with OSCC. Proinflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) have been suggested to play a certain role in variety of tumours. The aim of this study was to investigate the relationship of pretreatment serum IL-6 and TNF-α levels on tumour recurrence in patients with OSCC in order to identify potential biomarkers for the early detection of disease recurrence. The patients with newly diagnosed OSCC were treated and followed from the first visit from November 2006 until January 2008. Serum IL-6 and TNF-α concentrations were measured. The records of the patients were re-examined in July 2012 and data were recorded about cancer characteristics and tumour recurrence. Disease free survival was analyzed by Kaplan-Meier survival curves, log rank test and Cox proportional hazards regression. Serum IL-6 was shown as an independent risk factor for tumour recurrence. Pretreatment serum IL-6 concentration may be a useful biomarker for identification of OSCC patients with increased risk of the disease recurrence.

  15. Maternal plasma levels of interleukin-6, C-reactive protein, vitamins C, E and A, 8-isoprostane and oxidative status in women with preterm premature rupture of membranes.

    Science.gov (United States)

    Ilhan, Nevin; Celik, Ebru; Kumbak, Banu

    2015-02-01

    Preterm premature rupture of membranes (PPROM) is associated with significant maternal and perinatal morbidity. This study examined maternal oxidative stress in PPROM. This was a prospective cross-sectional study conducted in a university hospital. A total of 72 pregnant women were recruited into two groups, those with PPROM (38 cases) and those without PPROM (34 controls) matched for gestational age. Plasma interleukin-6, C-reactive protein, vitamins C, E and A, 8-isoprostane, total oxidant status (TOS) and antioxidant status (TAS) were determined for all study participants and the data were compared between the PPROM and control groups. Both case and control groups were comparably matched in age, parity, gestational age and smoking status. There was a significant association between low 8-isoprostane, low vitamin C and high total oxidant status and the occurrence of PPROM (p vitamin C and 8-isoprostane levels were lower and TOS higher in women with PPROM. Further research is needed to identify robust biological markers for the prevention and also prognosis of PPROM.

  16. Interleukin 6-174 G/C promoter and variable number of tandem repeats (VNTR) gene polymorphisms in sporadic Alzheimer's disease.

    Science.gov (United States)

    Capurso, Cristiano; Solfrizzi, Vincenzo; Colacicco, Anna Maria; D'Introno, Alessia; Frisardi, Vincenza; Imbimbo, Bruno P; Lorusso, Maria; Vendemiale, Gianluigi; Denitto, Marta; Santamato, Andrea; Seripa, Davide; Pilotto, Alberto; Fiore, Pietro; Capurso, Antonio; Panza, Francesco

    2010-02-01

    Previous studies examining the association between the interleukin 6 (IL-6)-174 C/G polymorphism and Alzheimer's disease (AD) have yielded conflicting results. Furthermore, the C allele of the IL-6 variable number of tandem repeats (VNTR) polymorphism was associated with a delayed onset and a decreased risk of AD. A total sample of 149 AD patients, and 298 age- and sex-matched unrelated caregivers from Apulia, southern Italy, were genotyped for the apolipoprotein E (APOE) polymorphism, the VNTR polymorphism in the 3' flanking region, and the -174G/C single-nucleotide polymorphism (SNP) in the promoter region of IL-6 gene on chromosome 7. Furthermore, we performed a haplotype analysis on these two polymorphisms on IL-6 locus. IL-6 VNTR and -174G/C allele and genotype frequencies were similar between AD patients and controls, also after stratification for late-onset (> or =65 years) and early-onset (VNTR and -174G/C polymorphisms, not supporting a previous reported additive effect of both IL-6 polymorphisms on AD risk. Our findings did not support a role of IL-6-174 G/C and IL-6 VNTR polymorphisms in the risk of sporadic AD in southern Italy, suggesting that these polymorphisms of IL-6 gene were at most weak genetic determinants of AD. Copyright 2009 Elsevier Inc. All rights reserved.

  17. Sesamin Modulates Tyrosine Hydroxylase, Superoxide Dismutase, Catalase, Inducible No Synthase and Interleukin-6 Expression in Dopaminergic Cells Under Mpp+-Induced Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Vicky Lahaie-Collins

    2008-01-01

    Full Text Available Oxidative stress is regarded as a mediator of nerve cell death in several neurodegenerative disorders, such as Parkinson's disease. Sesamin, a lignan mainly found in sesame oil, is currently under study for its anti-oxidative and possible neuroprotective properties. We used 1-methyl-4-phenyl-pyridine (MPP+ ion, the active metabolite of the potent parkinsonism-causing toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, to produce oxidative stress and neurodegeneration in neuronal PC12 cells, which express dopamine, as well as neurofilaments. Our results show that picomolar doses of sesamin protected neuronal PC12 cells from MPP+-induced cellular death, as revealed by colorimetric measurements and production of reactive oxygen species. We also demonstrated that sesamin acted by rescuing tyrosine hydroxylase levels from MPP+-induced depletion. Sesamin, however, did not modulate dopamine transporter levels, and estrogen receptor-alpha and -beta protein expression. By examining several parameters of cell distress, we found that sesamin also elicited a strong increase in superoxide dismutase activity as well as protein expression and decreased catalase activity and the MPP+ stimulated inducible nitric oxide synthase protein expression, in neuronal PC12 cells. Finally, sesamin possessed significant anti-inflammatory properties, as disclosed by its potential to reduce MPP+-induced interleukin-6 mRNA levels in microglia. From these studies, we determined the importance of the lignan sesamin as a neuroprotective molecule and its possible role in complementary and/or preventive therapies of neurodegenerative diseases.

  18. S-phase induction by interleukin-6 followed by chemotherapy in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Brown, P D; Diamant, Marcus; Jensen, P O

    1999-01-01

    Interleukin-6 (IL-6) has in vitro demonstrated growth regulatory effects on tumor cells from patients with chronic lymphocytic leukemia (CLL) and lymphoma. The proliferation rate of these cells is usually very low and this is thought to be one of the reasons for the lack of a curative potential....../kg and 10 micrograms/kg s.c. daily for 5 days followed by CHOP chemotherapy on the last day of rhIL-6 injection. Six patients had two treatment cycles. The proportion of cells in S-phase was determined by the bromodeoxyuridine labeling index (LI). Three patients achieved a partial remission, one patient had....../kg and 5 micrograms/kg respectively. Immunophenotypic assessment demonstrated that rhIL-6 increased the expression of CD20 in all CLL patients with a reversal after cessation of rhIL-6. We conclude that rhIL-6, in the dosage and schedule used in this study, did not increase the proportion of the cells in S...

  19. Human Mast Cells (HMC-1 5C6 Enhance Interleukin-6 Production by Quiescent and Lipopolysaccharide-Stimulated Human Coronary Artery Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Damandeep S. Walia

    2012-01-01

    Full Text Available We examined the effect of intact human mast cells (HMC-1 5C6 and their selected mediators on interleukin-6 (IL-6 production and bone morphogenetic protein-2 (BMP-2 expression in human coronary artery endothelial cells (HCAEC in the presence and absence of lipopolysaccharide (LPS. Scanning electron microscopy showed that HMC-1 5C6 cells adhere to HCAEC in cocultures. Addition of HMC-1 5C6 cells markedly enhanced the IL-6 production by quiescent and LPS-activated HCAEC even at the maximal concentration of LPS. Furthermore, mast cell-derived histamine and proteases accounted for the direct and synergistic effect of mast cells on IL-6 production that was completely blocked by the combination of histamine receptor-1 antagonist and protease inhibitors. Another novel finding is that histamine was able to induce BMP-2 expression in HCAEC. Collectively, our results suggest that endotoxin and mast cell products synergistically amplify vascular inflammation and that histamine participates in the early events of vascular calcification.

  20. Effects of Different Concentrations of Opium on the Secretion of Interleukin-6, Interferon-γ and Transforming Growth Factor Beta Cytokines from Jurkat Cells.

    Science.gov (United States)

    Asadikaram, Gholamreza; Igder, Somayeh; Jamali, Zahra; Shahrokhi, Nader; Najafipour, Hamid; Shokoohi, Mostafa; Jafarzadeh, Abdollah; Kazemi-Arababadi, Mohammad

    2015-01-01

    The risk of infectious, autoimmune and immunodeficiency diseases and cancers rise in opioid addicts due to changes in innate and acquired immune responses. Three types of opioid receptors (К-δ-μ) are expressed on the surface of lymphocytes and mononuclear phagocytes. The present study was designed to examine the effects of different concentrations of opium on the secretion of some cytokines produced by lymphocyte cells. Jurkat cells were exposed to different concentrations of opium for periods of 6, 24 and 72 h in cell culture medium. The amount of interleukin-6 (IL-6), interferon-γ (IFN-γ) and transforming growth factor-b (TGF-β) were then measured using enzyme-linked immunosorbent assay (ELISA) method. The results showed that opium increases the secretion of IL-6 in different concentration of opium in 6 h. The amount of IFN-γ decreased in 6 h and increased in 24 h significantly compared with control. On the other hand, opium had an inhibitory effect on the TGF-β secretion in 6, 24 and 72 h. Overall, the study showed that opium stimulates pro-inflammatory and suppressed anti-inflammatory cytokine secretion in Jurkat cells. This may account for the negative effect of opium on the immune system leading to chronic inflammation and a base for many disorders in opium addicts.

  1. Maternal serum interleukin-6 and its association with clinicopathological infectious morbidity in preterm premature rupture of membranes: a prospective cohort study.

    Science.gov (United States)

    Gulati, Shilpa; Agrawal, Swati; Raghunandan, Chitra; Bhattacharya, Jayashree; Saili, Arvind; Agarwal, Shilpi; Sharma, Deepika

    2012-08-01

    To analyze the association of maternal serum interleukin-6 (IL-6) with fetomaternal outcome in preterm premature rupture of membranes (PPROM). Serial serum IL-6 levels were measured in 45 women with PPROM at gestation 24-34 weeks. The women were followed till pueperium and fetomaternal outcome as well as the histopathology of the placenta and the umbilical cord was studied. The data were analyzed using t test and χ(2) test. IL-6 levels ≥ 8 pg/ml were significantly associated with puerperal sepsis and neonatal sepsis. Histological chorioamnionitis and funisitis were demonstrated in 48.8% and 13.3% women respectively and significantly correlated with elevated serum IL-6 levels and fetomaternal infection. A cut-off value of IL-6 of 8 pg/ml was found to correctly diagnose 19 out of 23 patients with infectious morbidity and showed the best sensitivity (82.6%) and specificity (86.3%) as compared to the total leucocycte count (TLC) and C-reactive protein (CRP) in diagnosing infection in PPROM. Maternal serum IL-6 can be used as a biomarker to predict preclinical asymptomatic infection in PPROM with good sensitivity and specificity.

  2. [Association between interleukin-6 polymorphism in the -174 G/C region and hearing loss in the elderly with a history of occupational noise exposure].

    Science.gov (United States)

    Braga, Miula Portelinha; Maciel, Sandra Mara; Marchiori, Luciana Lozza de Moraes; Poli-Frederico, Regina Célia

    2014-01-01

    The biological processes involved in noise-induced hearing loss (NIHL) are still unclear. The involvement of inflammation in this condition has been suggested. To investigate the association between interleukin - 6 (IL-6) polymorphism and susceptibility to NIHL. This was a cross-sectional study with a sample of 191 independent elderly individuals aged >60 years of age. Information on exposure to occupational noise was obtained by interviews. Audiological evaluation was performed using pure tone audiometry and genotyped through PCR by restriction fragment length polymorphism - PCR-RFLP. Data were analyzed using the chi-square test and the odds ratio (OR), with the significance level set at 5%. Among elderly with hearing loss (78.0%), 18.8% had a history of exposure to occupational noise. There was a statistically significant association between the genotype frequencies of the IL-6 -174 and NIHL. The elderly with the CC genotype were less likely to have hearing loss due to occupational noise exposure when compared to those carrying the GG genotype (OR=0.0124; 95% CI 0.0023-0.0671; phearing loss. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  3. Integrated gene and miRNA expression analysis of prostate cancer associated fibroblasts supports a prominent role for interleukin-6 in fibroblast activation.

    Science.gov (United States)

    Doldi, Valentina; Callari, Maurizio; Giannoni, Elisa; D'Aiuto, Francesca; Maffezzini, Massimo; Valdagni, Riccardo; Chiarugi, Paola; Gandellini, Paolo; Zaffaroni, Nadia

    2015-10-13

    Tumor microenvironment coevolves with and simultaneously sustains cancer progression. In prostate carcinoma (PCa), cancer associated fibroblasts (CAF) have been shown to fuel tumor development and metastasis by mutually interacting with tumor cells. Molecular mechanisms leading to activation of CAFs from tissue-resident fibroblasts, circulating bone marrow-derived fibroblast progenitors or mesenchymal stem cells are largely unknown. Through integrated gene and microRNA expression profiling, we showed that PCa-derived CAF transcriptome strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus proving evidence, for the first time, that the cytokine is able per se to induce most of the transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGFβ-related signatures, indicating that either signal, depending on the context, may concur to fibroblast activation. Our analyses also highlighted novel pathways potentially relevant for induction of a reactive stroma. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression.Overall, we provided insights into the molecular mechanisms driving fibroblast activation in PCa, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment.

  4. Human mast cells (HMC-1 5C6) enhance interleukin-6 production by quiescent and lipopolysaccharide-stimulated human coronary artery endothelial cells.

    Science.gov (United States)

    Walia, Damandeep S; Sharma, Mukut; Raveendran, Vineesh V; Zhou, Jianping; Sharma, Ram; Stechschulte, Daniel J; Dileepan, Kottarappat N

    2012-01-01

    We examined the effect of intact human mast cells (HMC-1 5C6) and their selected mediators on interleukin-6 (IL-6) production and bone morphogenetic protein-2 (BMP-2) expression in human coronary artery endothelial cells (HCAEC) in the presence and absence of lipopolysaccharide (LPS). Scanning electron microscopy showed that HMC-1 5C6 cells adhere to HCAEC in cocultures. Addition of HMC-1 5C6 cells markedly enhanced the IL-6 production by quiescent and LPS-activated HCAEC even at the maximal concentration of LPS. Furthermore, mast cell-derived histamine and proteases accounted for the direct and synergistic effect of mast cells on IL-6 production that was completely blocked by the combination of histamine receptor-1 antagonist and protease inhibitors. Another novel finding is that histamine was able to induce BMP-2 expression in HCAEC. Collectively, our results suggest that endotoxin and mast cell products synergistically amplify vascular inflammation and that histamine participates in the early events of vascular calcification.

  5. Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis.

    Science.gov (United States)

    Albrecht, Lea-Jessica; Tauber, Simone C; Merres, Julika; Kress, Eugenia; Stope, Matthias B; Jansen, Sandra; Pufe, Thomas; Brandenburg, Lars-Ove

    2016-01-01

    The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-α and the innate immune response in vivo in a model of Streptococcus pneumoniae-induced meningitis. For the experiments IL-6(-/-), TNFR1(-/-), and TNFR1-IL-6(-/-) KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1(-/-), IL-6(-/-), and TNFR1-IL-6(-/-) mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1(-/-) and TNFR1-IL-6(-/-) mice in contrast to IL-6(-/-) and wild type mice. Furthermore, the increased mortality of TNFR1(-/-) and TNFR1-IL-6(-/-) mice correlated with decreased glial cell activation compared to IL-6(-/-) or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone.

  6. Clinical significance of changes of plasma concentration of endothelium and serum levels of interleukin-6 and tumor necrosis factor in patients with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Xie Jianping; Zhang Guoyuan; Li Suping; Wu Chenxiu; Sun Yuejun; Yan Zongxun

    2003-01-01

    Objective: To determine the changes of plasma endothelium (ET) and serum interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) concentrations in patients with type 2 diabetes mellitus. Methods: Plasma ET and serum IL-6 and TNF-α levels were measured by radioimmunoassay in 61 cases of type 2 diabetes mellitus (DM) 36 without complication and 25 cases with complications and 33 controls. Results: (1) The plasma levels of ET and serum levels of IL-6 and TNF-α in patients with type 2 diabetes mellitus were significantly higher than those in the controls (p<0.01); (2) The blood levels of ET, TNF-α in patients with complications were significantly higher than those in patients without complications (p<0.02); (3) The blood levels of ET, IL-6 and TNF-α were mutually positively correlated. Conclusion: Monitoring of ET, IL-6 and TNF-α levels in diabetic patients can provide additional valuable information for assessing the course of disease and efficacy of management

  7. Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: association with asymptomatic inflammatory prostatitis NIH category IV.

    Science.gov (United States)

    Engelhardt, Paul Friedrich; Seklehner, Stephan; Brustmann, Hermann; Lusuardi, Lukas; Riedl, Claus R

    2015-04-01

    This study prospectively investigated the immunohistochemical expression of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) in patients with prostate cancer and benign prostatic hyperplasia (BPH), and a possible association of these conditions with asymptomatic inflammatory prostatitis National Institutes of Health (NIH) category IV. The study included 139 consecutive patients who underwent transurethral resection of the prostate and transvesical enucleation of the prostate (n = 82) or radical prostatectomy (n = 57). To characterize inflammatory changes the criteria proposed by Irani et al. [J Urol 1997;157:1301-3] were used. IL-2R and IL-6 expression was studied by a standard immunohistochemical method. Results were correlated with tumour, node, metastasis stage, Gleason scores, total prostate-specific antigen, International Prostate Symptom Score and body mass index. IL-2R and IL-6 expression was significantly higher in neoplastic prostate cancer tissue than in normal tissue of prostate cancer patients (p Prostate cancer patients with prostatitis showed significantly higher IL-2R expression than those without inflammation (p prostatitis than in those without (p prostate cancer tissue than in normal tissue. Patients with asymptomatic inflammatory prostatitis NIH category IV showed significantly greater activity.

  8. Melatonin inhibits Prevotella intermedia lipopolysaccharide-induced production of nitric oxide and interleukin-6 in murine macrophages by suppressing NF-κB and STAT1 activity.

    Science.gov (United States)

    Choi, Eun-Young; Jin, Ji-Young; Lee, Ju-Youn; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2011-03-01

    Although a range of biological and pharmacological activities of melatonin have been reported, little is known about its potential anti-inflammatory efficacy in periodontal disease. In this study, we investigated the effects of melatonin on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory reactions in the periodontium, and sought to determine the underlying mechanisms of action. Melatonin suppressed the production of nitric oxide (NO) and interleukin-6 (IL-6) at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. P. intermedia LPS-induced NF-κB-dependent luciferase activity was significantly inhibited by melatonin. Melatonin did not reduce NF-κB transcriptional activity at the level of IκB-α degradation. Melatonin blocked NF-κB signaling through the inhibition of nuclear translocation and DNA-binding activity of NF-κB p50 subunit and suppressed STAT1 signaling. Although further research is required to clarify the detailed mechanism of action, we conclude that melatonin may contribute to blockade of the host-destructive processes mediated by these two proinflammatory mediators and could be a highly efficient modulator of host response in the treatment of inflammatory periodontal disease. © 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S.

  9. Alkaline phosphatase expression in cultured endothelial cells of aorta and brain microvessels: induction by interleukin-6-type cytokines and suppression by transforming growth factor betas.

    Science.gov (United States)

    Nakazato, H; Deguchi, M; Fujimoto, M; Fukushima, H

    1997-01-01

    Alkaline phosphatase (ALP) activity is markedly high in endothelial cells of the blood-brain barrier (BBB) type but absent from or low in those of the non-BBB type. Interleukin 6 (IL-6) has been identified as a glial cell line-derived factor that induces high ALP activity in cultured aortic endothelial cells. In the present study, we examined the effect of IL-6-type cytokines and transforming growth factor betas (TGF-betas) on ALP expression in cultures of calf pulmonary aortic endothelial (CPAE) cells and porcine brain microvascular endothelial (PBME) cells. Leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M, which are known as IL-6-type cytokines, induced high ALP expression in the CPAE cells but not in the PBME cells. ALP levels in these cells were markedly suppressed by culture with TGF-betas. However, in cultured PBME cells, IL-6 and a derivative of cyclic adenosine monophosphate significantly increased ALP activity. Our findings raise the posibility that local concentrations of IL-6, IL-6-type cytokines, and TGF-betas affect the ALP levels in the endothelial cells of aorta and brain microvessels under normal development and also under inflammatory conditions.

  10. Accuracy of a combined insulin-like growth factor-binding protein-1/interleukin-6 test (Premaquick) in predicting delivery in women with threatened preterm labor.

    Science.gov (United States)

    Eleje, George Uchenna; Ezugwu, Euzebus Chinonye; Eke, Ahizechukwu Chigoziem; Eleje, Lydia Ijeoma; Ikechebelu, Joseph Ifeanyichukwu; Ezebialu, Ifeanyichukwu Uzoma; Obiora, Chukwudi Celestine; Nwosu, Betrand Obi; Ezeama, Chukwuemeka Okwudili; Udigwe, Gerald Okanandu; Okafor, Charles Ikechukwu; Ezugwu, Frank Okechukwu

    2017-11-27

    To determine values of combinations of interleukin-6 (IL-6)/cervical native insulin-like growth factor-binding protein-1 (IGFBP-1)/total IGFBP-1 (Premaquick©) in predicting spontaneous deliveries and spontaneous exclusive preterm deliveries in women with threatened preterm labor. Women with singleton pregnancies between gestation age (GA) of 24 weeks and 36 weeks and 6 days with preterm labor were recruited during a prospective multicenter study. Premaquick© was positive when at least two of three biomarkers were positive. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were estimated for both prediction of spontaneous deliveries and spontaneous exclusive preterm deliveries. Ninety-seven (99.0%) out of 98 women enrolled were analyzed. Based on delivery status 7/14 days post-enrollment of general study population, Premaquick© had a sensitivity of 87.1/85.7%, a specificity of 92.4/96.8%, a PPV of 84.4/93.8% and a NPV of 93.9/92.3% for prediction of spontaneous delivery. Predictive accuracy of Premaquick© test in relation to days of enrollment were: 90.7% (≤7 days) and 92.8% (≤14 days). For women enrolled at GA preterm delivery within 7/14 days of enrollment, respectively. PPV was most significantly different in both groups when outcomes were compared between 2 days and 14 days post-enrollment (Ppreterm deliveries in threatened preterm labor in singleton pregnancies.

  11. Effect of maternal and neonatal interleukin-6 - 174 G/C polymorphism on preterm birth and neonatal morbidity.

    Science.gov (United States)

    Karakaş, N Mutlu; Ecevit, Ayse N; Yalçın, Yaprak; Özdemir, Beril; Verdi, Hasibe; Tekindal, M Ağah; Özbek, Namık Y; Tarcan, Aylin; Ataç, Fatma B; Haberal, Ali

    2018-04-01

    The aim of this study was to analyze maternal and neonatal interleukin 6 (IL-6) (-174 G/C) polymorphism and to determine effect on preterm birth and neonatal morbidity. One hundred and sixty-four mothers (100 term births, 64 preterm births) and 183 newborn infants who were 100 healthy term and 83 preterm babies followed in newborn intensive care units were evaluated. PCR-RFLP was performed for IL-6 (-174 G/C) genotyping. The rate of GG genotype in mothers of term and preterm infants were 54% (n = 54/100), 75% (n = 48/64), respectively (p > .05) and the rate of GC + CC genotype was 46% (n = 46/100) and 25% (n = 16/64) in mothers giving term and preterm birth (PTB), respectively (p preterm infants, respectively. GC + CC genotype was 35% (n = 35/100) in term infants and 18.1% (n = 15/83) in preterm infants (p preterm birth. The presence of polymorphism is protective against preterm birth and was not associated with neonatal outcome.

  12. Effects of confinement on physiological and psychological responses and expression of interleukin 6 and brain derived neurotrophic factor mRNA in primiparous and multiparous weaning sows.

    Science.gov (United States)

    Zhang, Mingyue; Li, Xiang; Li, Jianhong; Sun, Hanqing; Zhang, Xiaohui; Bao, Jun

    2017-09-01

    The present study aimed to investigate whether the long-lasting, recurrent restricting of sows leads to the physiological and psychological reaction of discomfort. Sows (Large White) that had experienced restricting for about 0.5 or 3 years and age-matched sows kept in a group housing system (loose sows) were compared. Pupillary light reflex parameters were measured at the weaning stage. Immediately after slaughter, blood samples were taken to measure serum cortisol levels, and the brain was dissected, gene expression in the hippocampus, frontal cortex and hypothalamus was analyzed. The serum cortisol levels were higher in the confined sows than in the loose sows. The full maturity, but not the young adolescent, confined sows had longer latency time in the onset of pupil constriction than their loose counterparts. Real-time polymerase chain reaction analyses revealed an increased expression of interleukin 6 mRNA in the hippocampus and decreased expression of brain derived neurotrophic factor mRNA in hippocampus and hypothalamus and to a lesser extent in the frontal cortex of the full maturity confined sows, compared with the full maturity loose sows. Taken together, these data indicated that recurrent restricting stress in full maturity sows leads to the physiological and psychological reaction of discomfort.

  13. Effects of confinement on physiological and psychological responses and expression of interleukin 6 and brain derived neurotrophic factor mRNA in primiparous and multiparous weaning sows

    Directory of Open Access Journals (Sweden)

    Mingyue Zhang

    2017-09-01

    Full Text Available Objective The present study aimed to investigate whether the long-lasting, recurrent restricting of sows leads to the physiological and psychological reaction of discomfort. Methods Sows (Large White that had experienced restricting for about 0.5 or 3 years and age-matched sows kept in a group housing system (loose sows were compared. Pupillary light reflex parameters were measured at the weaning stage. Immediately after slaughter, blood samples were taken to measure serum cortisol levels, and the brain was dissected, gene expression in the hippocampus, frontal cortex and hypothalamus was analyzed. Results The serum cortisol levels were higher in the confined sows than in the loose sows. The full maturity, but not the young adolescent, confined sows had longer latency time in the onset of pupil constriction than their loose counterparts. Real-time polymerase chain reaction analyses revealed an increased expression of interleukin 6 mRNA in the hippocampus and decreased expression of brain derived neurotrophic factor mRNA in hippocampus and hypothalamus and to a lesser extent in the frontal cortex of the full maturity confined sows, compared with the full maturity loose sows. Conclusion Taken together, these data indicated that recurrent restricting stress in full maturity sows leads to the physiological and psychological reaction of discomfort.

  14. Circulating and broncho-alveolar interleukin-6 in relation to body temperature in an experimental model of bovine Chlamydia psittaci infection.

    Directory of Open Access Journals (Sweden)

    Annette Prohl

    Full Text Available In rodent models of experimentally induced fever, the important role of interleukin-6 (IL-6 as a circulating endogenous pyrogen is well established. Studies employing larger animal species and real infections are scarce. Therefore, we assessed bioactive IL-6 in peripheral blood and in broncho-alveolar lavage fluid (BALF of calves after intra-bronchial inoculation with vital Chlamydia psittaci (Cp, with inactivated Cp, or with BGM cells. Only calves inoculated with vital Cp developed fever (peak at 2-3 days after challenge and significantly increased IL-6 activity. Controls inoculated with either inactivated Cp or BGM cells also expressed increased bioactive IL-6, but no fever developed. Activity of IL-6 in BALF was significantly higher compared to blood serum. This experimental model of Cp infection revealed no apparent relation between IL-6 in blood and body temperature, but did reveal a relation between IL-6 and other markers of inflammation in BALF. We conclude that a local inflammatory response in the lungs of infected calves caused fever, which developed by mechanisms including other mediators besides IL-6.

  15. Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum

    NARCIS (Netherlands)

    Prins, J. M.; Kuijper, E. J.; Mevissen, M. L.; Speelman, P.; van Deventer, S. J.

    1995-01-01

    The concentration and accessibility of endotoxin can increase following antibiotic killing of gram-negative bacteria. There are indications that antibiotics may differ in this respect. We measured endotoxin levels in RPMI 1640 and tumor necrosis factor alpha (TNF-alpha) and interleukin-6 production

  16. Induced illness in interleukin-6 (IL-6) knock-out mice: a causal role of IL-6 in the development of the low 3,5,3'-triiodothyronine syndrome

    NARCIS (Netherlands)

    Boelen, A.; Maas, M. A.; Lowik, C. W.; Platvoet, M. C.; Wiersinga, W. M.

    1996-01-01

    Interleukin-6 (IL-6) administration to human subjects or experimental animals induces changes in thyroid hormone metabolism resembling those in the sick euthyroid syndrome. Furthermore, the decrease in serum T3 during illness is significantly related to serum IL-6 concentrations. These findings

  17. Beneficial Effects of Anti-Interleukin-6 Antibodies on Impaired Gastrointestinal Motility, Inflammation and Increased Colonic Permeability in a Murine Model of Sepsis Are Most Pronounced When Administered in a Preventive Setup.

    Directory of Open Access Journals (Sweden)

    Sara Nullens

    Full Text Available During sepsis, gastrointestinal ileus, mucosal barrier dysfunction and bacterial translocation are accepted to be important triggers that can maintain or exacerbate the septic state. In the caecal ligation and puncture animal model of sepsis, we demonstrated that systemic and colonic interleukin-6 levels are significantly increased coinciding with an impaired colonic barrier function. We therefore aimed to study the effect of therapeutic or curative administration of anti-IL6 antibodies on overall GI motility, colonic permeability and translocation of intestinal bacteria in blood and mesenteric lymph nodes in the mouse caecal ligation and puncture model.OF-1 mice were randomized to either the preventive or curative protocol, in which they received 1 mg/kg of antibodies to interleukin-6, or its IgG isotype control solution. They subsequently underwent either the caecal ligation and puncture procedure, or sham-surgery. GI motility was assessed 48 h following the procedure, as well as colonic permeability, serum and colon cytokines, colonic tight junction proteins at the mRNA level; cultures of blood and mesenteric lymph nodes were performed.Preventive administration of anti-interleukin-6 antibodies successfully counteracted the gastrointestinal motility disturbances and impaired colonic barrier function that could be observed in vehicle-treated septic animals. Serum and colonic levels of proinflammatory cytokines were significantly lower when animals were preventively treated with anti-interleukin-6 antibodies. A repetitive injection 24 h later resulted in the most pronounced effects. Curative treatment significantly lowered systemic and colonic inflammation markers while the effects on transit and permeability were unfortunately no longer significant.Caecal ligation and puncture resulted in septic ileus with an increased colonic permeability. Antibodies to interleukin-6 were able to ameliorate gastro-intestinal motility, suppress inflammation and

  18. Combination therapy efficacy of catgut embedding acupuncture and diet intervention on interleukin-6 levels and body mass index in obese patients

    Science.gov (United States)

    Tjan, P. M.; Srilestari, A.; Abdurrohim, K.; Kresnawan, T.

    2017-08-01

    Obesity is a major health problem worldwide, affecting more than 500 million adults with an additional 1.5 billion adults classified as overweight. Acupuncture has been recognized as an adjunctive therapy for obesity, and recent evidence suggests its potential to reduce the inflammatory response in adipose tissue, a condition believed to be responsible for obesity-related health problems. Interleukin-6 (IL-6) has been proposed as an important mediator of the inflammatory response in adipose tissue, but the number of studies addressing the issue is still limited. A double-blind, randomized, placebo-controlled trial was conducted with36 obese patients currently receiving dietary intervention. The patients were randomly allocated into the catgut embedding acupuncture group with diet intervention or the sham (placebo) embedding acupuncture group with diet intervention. Catgut embedding therapy was given twice at CV12 Zhongwan, ST25 Tianshu, CV6 Qihai, and SP6 Sanyinjiao acupoints with two week intervals between procedures. The study endpoints were the IL-6 levels in the blood plasma and body mass index (BMI), measured before and after the intervention. We observed a reduction in the IL-6 levels (mean reduction 0.13 pg/mL, 95% CI: 0.03-0.23) and BMI (mean reduction 0.66, 95% CI 0.43-0.88) in the accupuncture group. The average difference in mean reduction of BMI between the accupuncture and sham groups was 0.34 (95% CI: 0.17-0.52). No difference was found in mean IL-6 reduction between the two groups (95% CI: -0.17 to 0.06). The results suggest that acupoint catgut embedding therapy may help reduce IL-6 levels and BMI in obese patients receiving dietary intervention.

  19. Impact of fasting followed by short-term exposure to interleukin-6 on cytochrome P450 mRNA in mice.

    Science.gov (United States)

    Rasmussen, Martin Krøyer; Bertholdt, Lærke; Gudiksen, Anders; Pilegaard, Henriette; Knudsen, Jakob G

    2018-01-05

    The gene expression of the cytochrome P450 (CYP) enzyme family is regulated by numerous factors. Fasting has been shown to induce increased hepatic CYP mRNA in both humans and animals. However, the coordinated regulation of CYP, CYP-regulating transcription factors, and transcriptional co-factors in the liver linking energy metabolism to detoxification has never been investigated. Interleukin-6 (IL-6) has been suggested to be released during fasting and has been shown to regulate CYP expression. The present study investigated the hepatic mRNA content of selected CYP, AhR, CAR, PXR and PPARα in mice fasted for 18h and subsequently exposed to IL-6. Furthermore, the impact of fasting on PGC-1α, HNF-4α, SIRT1 and SIRT3 mRNA was examined. Fasting induced a marked increase in Cyp2b10, Cyp2e1 and Cyp4a10 mRNA, while CYP1a1, Cyp1a2, Cyp2a4 and Cyp3a11 mRNA levels remained unchanged. In accordance, the mRNA levels of CAR and PPARα were also increased with fasting. The PGC-1α, SIRT1 and SIRT3 mRNA levels were also increased after fasting, while the HNF-4α mRNA levels remained unchanged. In mice subjected to IL-6 injection, the fasting-induced PXR, PPARα and PGC-1α mRNA responses were lower than after saline injection. In conclusion, fasting was demonstrated to be a strong inducer of hepatic CYP mRNA as well as selected transcription factors controlling the expression of the investigated CYP. Moreover, the mRNA levels of transcriptional co-factors acting as energy sensors and co-factors for CYP regulation was also increased in the liver, suggesting crosstalk at the molecular level between regulation of energy metabolism and detoxification. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. S100A8/A9 (Calprotectin, Interleukin-6, and C-Reactive Protein in Obesity and Diabetes before and after Roux-en-Y Gastric Bypass Surgery

    Directory of Open Access Journals (Sweden)

    Louise Lylloff

    2017-08-01

    Full Text Available Background: In obesity, which is a major contributor to insulin resistance and diabetes, the circulating level of S100A8/A9 (calprotectin is elevated and declines after Roux-en-Y gastric bypass surgery (RYGB. However, studies on S100A8/A9 and the pathophysiological mechanisms in insulin resistance and diabetes are few and contradictory. Methods: We studied 48 subjects who underwent RYGB, comprising a non-diabetic control group and two diabetic groups in whom diabetes either regressed or persisted, 6-12 months post-surgically. S100A8/A9, interleukin 6 (IL-6 as well as other inflammatory and diabetes-related markers were measured pre- and post-surgically. Results: Significant and similar decreases of BMI were found in all groups. S100A8/A9 and IL-6 decreased significantly in the group with diabetes remission and in the control group, but not in the group with persistent diabetes. The relative changes in S100A8/A9 and IL-6 correlated significantly (r = 0.905, p = 0.005 only in the group with persistent diabetes. In contrast, leukocyte count and C-reactive protein correlated significantly to S100A8/A9 only in the control group. Conclusion: Our study is suggestive of S100A8/A9 and IL-6 being related to a persistent diabetes status post-surgically and of different pathophysiological mechanisms being involved in the post-surgical changes in the three groups, despite similar decreases in BMI.

  1. Association of Peripheral Interleukin-6 with Global Cognitive Decline in Non-demented Adults: A Meta-Analysis of Prospective Studies

    Directory of Open Access Journals (Sweden)

    Steven Bradburn

    2018-01-01

    Full Text Available Background: Elevated biomarkers of systemic inflammation have been reported in individuals with cognitive decline, however, most of the literature concerns cross-sectional analyses that have produced mixed results. This study investigates the etiology of this association by performing meta-analyses on prospective studies investigating the relationship between baseline interleukin-6 (IL-6, an established marker of peripheral inflammation, with cognitive decline risk in non-demented adults at follow-up.Methods: We reviewed studies reporting peripheral IL-6 with future cognitive decline, up to February 2017 by searching the PubMed, Science Direct, Scopus and Google Scholar databases. Studies which contained odds ratios (ORs for the association between circulating baseline IL-6 and longitudinal cognitive performance in non-demented community dwelling older adults were pooled in random-effects models.Results: The literature search retrieved 5,642 potential articles, of which 7 articles containing 8 independent aging cohorts were eligible for review. Collectively, these studies included 15,828 participants at baseline. Those with high circulating IL-6 were 1.42 times more likely to experience global cognitive decline at follow-up, over a 2–7-year period, compared to those with low IL-6 (OR 1.42, 95% CI 1.18–1.70; p < 0.001. Subgroup and sensitivity analyses suggests that this association is independent of the study sample size, duration of follow-up and cognitive assessments used.Conclusions: These results add further evidence for the association between high peripheral inflammation, as measured by blood IL-6, and global cognitive decline. Measuring circulating IL-6 may be a useful indication for future cognitive health.

  2. A system model of the effects of exercise on plasma Interleukin-6 dynamics in healthy individuals: Role of skeletal muscle and adipose tissue.

    Directory of Open Access Journals (Sweden)

    Micaela Morettini

    Full Text Available Interleukin-6 (IL-6 has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1 from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution. This study aimed at developing and validating a system model of exercise's effects on plasma IL-6 dynamics in healthy humans, combining the contributions of both adipose tissue and skeletal muscle. A two-compartment description was adopted to model plasma IL-6 changes in response to oxygen uptake's variation during an exercise bout. The free parameters of the model were estimated by means of a cross-validation procedure performed on four different datasets. A low coefficient of variation (<10% was found for each parameter and the physiologically meaningful parameters were all consistent with literature data. Moreover, plasma IL-6 dynamics during exercise and post-exercise were consistent with literature data from exercise protocols differing in intensity, duration and modality. The model successfully emulated the physiological effects of exercise on plasma IL-6 levels and provided a reliable description of the role of skeletal muscle and adipose tissue on the dynamics of plasma IL-6. The system model here proposed is suitable to simulate IL-6 response to different exercise modalities. Its future integration with existing models of GLP-1-induced insulin secretion might provide a more reliable description of exercise's effects on glucose homeostasis and hence support the definition of more tailored interventions for the treatment of type 2 diabetes.

  3. Multiple lipopolysaccharide (LPS) injections alter interleukin 6 (IL-6), IL-7, IL-10 and IL-6 and IL-7 receptor mRNA in CNS and spleen.

    Science.gov (United States)

    Szot, Patricia; Franklin, Allyn; Figlewicz, Dianne P; Beuca, Timothy Petru; Bullock, Kristin; Hansen, Kim; Banks, William A; Raskind, Murray A; Peskind, Elaine R

    2017-07-04

    Neuroinflammation is proposed to be an important component in the development of several central nervous system (CNS) disorders including depression, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, exactly how neuroinflammation leads to, or contributes to, these central disorders is unclear. The objective of the study was to examine and compare the expression of mRNAs for interleukin-6 (IL-6), IL-7, IL-10 and the receptors for IL-6 (IL-6R) and IL-7 (IL-7R) using in situ hybridization in discrete brain regions and in the spleen after multiple injections of 3mg/kg lipopolysaccharide (LPS), a model of neuroinflammation. In the spleen, LPS significantly elevated IL-6 mRNA expression, then IL-10 mRNA, with no effect on IL-7 or IL-7R mRNA, while significantly decreasing IL-6R mRNA expression. In the CNS, LPS administration had the greatest effect on IL-6 and IL-6R mRNA. LPS increased IL-6 mRNA expression only in non-neuronal cells throughout the brain, but significantly elevated IL-6R mRNA in neuronal populations, where observed, except the cerebellum. LPS resulted in variable effects on IL-10 mRNA, and had no effect on IL-7 or IL-7R mRNA expression. These studies indicate that LPS-induced neuroinflammation has substantial but variable effects on the regional and cellular patterns of CNS IL-6, IL-7 and IL-10, and for IL-6R and IL-7R mRNA expression. It is apparent that administration of LPS can affect non-neuronal and neuronal cells in the brain. Further research is required to determine how CNS inflammatory changes associated with IL-6, IL-10 and IL-6R could in turn contribute to the development of CNS neurological disorders. Published by Elsevier Ltd.

  4. A system model of the effects of exercise on plasma Interleukin-6 dynamics in healthy individuals: Role of skeletal muscle and adipose tissue.

    Science.gov (United States)

    Morettini, Micaela; Palumbo, Maria Concetta; Sacchetti, Massimo; Castiglione, Filippo; Mazzà, Claudia

    2017-01-01

    Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution. This study aimed at developing and validating a system model of exercise's effects on plasma IL-6 dynamics in healthy humans, combining the contributions of both adipose tissue and skeletal muscle. A two-compartment description was adopted to model plasma IL-6 changes in response to oxygen uptake's variation during an exercise bout. The free parameters of the model were estimated by means of a cross-validation procedure performed on four different datasets. A low coefficient of variation (dynamics during exercise and post-exercise were consistent with literature data from exercise protocols differing in intensity, duration and modality. The model successfully emulated the physiological effects of exercise on plasma IL-6 levels and provided a reliable description of the role of skeletal muscle and adipose tissue on the dynamics of plasma IL-6. The system model here proposed is suitable to simulate IL-6 response to different exercise modalities. Its future integration with existing models of GLP-1-induced insulin secretion might provide a more reliable description of exercise's effects on glucose homeostasis and hence support the definition of more tailored interventions for the treatment of type 2 diabetes.

  5. Effect of marine-derived n-3 polyunsaturated fatty acids on C-reactive protein, interleukin 6 and tumor necrosis factor α: a meta-analysis.

    Science.gov (United States)

    Li, Kelei; Huang, Tao; Zheng, Jusheng; Wu, Kejian; Li, Duo

    2014-01-01

    Previous studies did not draw a consistent conclusion about the effects of marine-derived n-3 polyunsaturated fatty acids (PUFAs) on fasting blood level of C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). A comprehensive search of Web of Science, PubMed, Embase and Medline (from 1950 to 2013) and bibliographies of relevant articles was undertaken. Sixty-eight RCTs with a total of 4601 subjects were included in the meta-analysis. Marine-derived n-3 PUFAs supplementation showed a lowering effect on Marine-derived n-3 PUFAs supplementation had a significant lowering effect on TNF-α, IL-6 and CRP in three groups of subjects (subjects with chronic non-autoimmune disease, subjects with chronic autoimmune disease and healthy subjects). A significant negative linear relationship between duration and effect size of marine-derived n-3 PUFAs supplementation on fasting blood levels of TNF-α and IL-6 in subjects with chronic non-autoimmune disease was observed, indicating that longer duration of supplementation could lead to a greater lowering effect. A similar linear relationship was also observed for IL-6 levels in healthy subjects. Restricted cubic spline analysis and subgroup analysis showed that the lowering effect of marine-derived n-3 PUFAs on CRP, IL-6 and TNF-α in subjects with chronic non-autoimmune disease became weakened when body mass index was greater than 30 kg/m². The effect of marine-derived n-3 PUFAs from dietary intake was only assessed in subjects with chronic non-autoimmune disease, and a significant lowering effect was observed on IL-6, but not on CRP and TNF-α. Marine-derived n-3 PUFAs supplementation had a significant lowering effect on CRP, IL-6 and TNF-α level. The lowering effect was most effective in non-obese subjects and consecutive long-term supplementation was recommended.

  6. Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

    LENUS (Irish Health Repository)

    Dowdall, J F

    2012-02-03

    The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

  7. Role of maca (Lepidium meyenii) consumption on serum interleukin-6 levels and health status in populations living in the Peruvian Central Andes over 4000 m of altitude.

    Science.gov (United States)

    Gonzales, Gustavo F; Gasco, Manuel; Lozada-Requena, Ivan

    2013-12-01

    Lepidium meyenii (Maca) is a plant that grows at over 4,000 m above sea level in the central Peruvian Andes. The hypocotyls of this plant are traditionally consumed for their nutritional and medicinal properties. The aim of this study was to determine the health status based on a health related quality of life (HRQL) questionnaire (SF-20) and serum levels of interleukin 6 (IL-6) in subjects that are maca consumers. For this, a cross-sectional study was designed to be performed in 50 subjects from Junin (4,100 m): 27 subjects were maca consumers and 23 were non-consumers. The SF-20 survey is used to obtain a summary measure of health status. The stand up from a chair and sit down (SUCSD) test (to assess lower-extremity function), hemoglobin measurement, blood pressure, sexual hormone levels, serum IL-6 levels and the score of chronic mountain sickness (CMS) were evaluated. Testosterone/estradiol ratio (P <0.05), IL-6 (P < 0.05) and CMS score were lower, whereas the health status score was higher, in maca consumers when compared to non-consumers (P < 0.01). A greater proportion of maca consumers successfully completed the SUCSD test compared to non-consumers (P < 0.01), showing a significant association with lower values of serum IL-6 (P < 0.05). In conclusion, consumption of maca was associated with low serum IL-6 levels and in turn with better health status scores in the SF-20 survey and low chronic mountain sickness scores.

  8. Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats

    Science.gov (United States)

    Mohammadi, Shima; Karimzadeh Bardei, Latifeh; Hojati, Vida; Ghorbani, Azita; Nabiuni, Mohammad

    2017-01-01

    Objective Curcumin protects the liver against injury and fibrosis through suppressing hepatic inflammation, attenuating hepatic oxidative stress (OS), and inhibiting hepatic stellate cells (HSCs) activation. Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are considered as common metabolic disorders. Low-grade chronic inflammation with different markers, such as elevated C-reactive protein (CRP) and interleukin-6 (IL-6) levels, play a crucial role in PCOS. This study aimed to evaluate the therapeutic effects of curcumin on IL-6 and CRP levels as well as insulin resistance (IR) index on liver function in PCOS rats. Materials and Methods In this experimental study, 90 adult Wistar rats were divided into control (n=18), sham (n=18), PCOS (n=18) and curcumin-treated PCOS groups (n=36). PCOS group was injected subcutaneously with 2 mg estradio-valerate (E2V). After 60 days, PCOS group was treated with curcumin [100 and 300 mg/kg body weight (BW)] for 14 days and anesthetized by chloroform. Blood and liver samples were collected for histological and serological analyses. Data were analyzed using In-Stat 3 via one-way analysis of variance (ANOVA). Results Histological and serological analyses showed a reduction in number of necrotic cells, IR index, as well as IL-6 and CRP levels in PCOS rats that were treated with various concentrations of curcumin. Conclusion In this study, curcumin decreased liver inflammation by induction of insulin sensitivity and reduction of hepatic necrosis. Therefore, curcumin may be considered as protective factor against inflammatory state of PCOS. PMID:28836404

  9. Brucella abortus Inhibits Major Histocompatibility Complex Class II Expression and Antigen Processing through Interleukin-6 Secretion via Toll-Like Receptor 2▿

    Science.gov (United States)

    Barrionuevo, Paula; Cassataro, Juliana; Delpino, M. Victoria; Zwerdling, Astrid; Pasquevich, Karina A.; Samartino, Clara García; Wallach, Jorge C.; Fossati, Carlos A.; Giambartolomei, Guillermo H.

    2008-01-01

    The strategies that allow Brucella abortus to survive inside macrophages for prolonged periods and to avoid the immunological surveillance of major histocompatibility complex class II (MHC-II)-restricted gamma interferon (IFN-γ)-producing CD4+ T lymphocytes are poorly understood. We report here that infection of THP-1 cells with B. abortus inhibited expression of MHC-II molecules and antigen (Ag) processing. Heat-killed B. abortus (HKBA) also induced both these phenomena, indicating the independence of bacterial viability and involvement of a structural component of the bacterium. Accordingly, outer membrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, inhibited both MHC-II expression and Ag processing to the same extent as HKBA. Moreover, a synthetic lipohexapeptide that mimics the structure of the protein lipid moiety also inhibited MHC-II expression, indicating that any Brucella lipoprotein could down-modulate MHC-II expression and Ag processing. Inhibition of MHC-II expression and Ag processing by either HKBA or lipidated Omp19 (L-Omp19) depended on Toll-like receptor 2 and was mediated by interleukin-6. HKBA or L-Omp19 also inhibited MHC-II expression and Ag processing of human monocytes. In addition, exposure to the synthetic lipohexapeptide inhibited Ag-specific T-cell proliferation and IFN-γ production of peripheral blood mononuclear cells from Brucella-infected patients. Together, these results indicate that there is a mechanism by which B. abortus may prevent recognition by T cells to evade host immunity and establish a chronic infection. PMID:17984211

  10. TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner

    Directory of Open Access Journals (Sweden)

    S.-Y. Guo

    2007-05-01

    Full Text Available The tissue inhibitor of metalloproteinases (TIMP-1 is a multifunctional protein which is not only an inhibitor of matrix metalloproteinases (MMPs but also to have a possible "cytokine-like" action. Here, we first compared mRNA expression of TIMP-1 and MMP-9 in BEL-7402 (a hepatocellular carcinoma cell line, L-02 (a normal liver cell line and QSG-7701 (a cell line derived from peripheral tissue of liver carcinoma using real-time quantitative RT-PCR. By evaluating the variation of the MMP-9/TIMP-1 ratio as an index of reciprocal changes of the expression of the two genes, we observed that the MMP-9/TIMP-1 ratio was about 13- and 5-fold higher in BEL-7402 than in L-02 and QSG-7701, respectively. Significantly, overexpression of TIMP-1 decreased the MMP-9/TIMP-1 ratio in BEL-7402 and then inhibited the cell growth to 60% and reduced the migration to about 30%. Meanwhile, our data showed that interleukin-6 (IL-6 (100 ng/mL could also inhibited the cell growth of BEL-7402. Further studies indicated that TIMP-1 mediated the inhibitory effect of IL-6 on BEL-7402 cell proliferation in a STAT3-dependent manner, which could further accelerate the expression of the cyclin-dependent kinase inhibitor p21. A dominant negative STAT3 mutant totally abolished IL-6-induced TIMP-1 expression and its biological functions. The present results demonstrate that TIMP-1 may be one of the mediators that regulate the inhibitory effect of IL-6 on BEL-7402 proliferation in which STAT3 signal transduction and p21 up-regulation also play important roles.

  11. Directed evolution of a three-finger neurotoxin by using cDNA display yields antagonists as well as agonists of interleukin-6 receptor signaling

    Directory of Open Access Journals (Sweden)

    Naimuddin Mohammed

    2011-01-01

    Full Text Available Abstract Background Directed evolution of biomolecules such as DNA, RNA and proteins containing high diversity has emerged as an effective method to obtain molecules for various purposes. In the recent past, proteins from non-immunoglobulins have attracted attention as they mimic antibodies with respect to binding potential and provide further potential advantages. In this regard, we have attempted to explore a three-finger neurotoxin protein (3F. 3F proteins are small (~7 kDa, structurally well defined, thermally stable and resistant to proteolysis that presents them as promising candidates for directed evolution. Results We have engineered a snake α-neurotoxin that belongs to the 3F family by randomizing the residues in the loops involved in binding with acetylcholine receptors and employing cDNA display to obtain modulators of interleukin-6 receptor (IL-6R. Selected candidates were highly specific for IL-6R with dissociation constants and IC50s in the nanomolar range. Antagonists as well as agonists were identified in an IL-6 dependent cell proliferation assay. Size minimization yielded peptides of about one-third the molecular mass of the original proteins, without significant loss of activities and, additionally, lead to the identification of the loops responsible for function. Conclusions This study shows 3F protein is amenable to introduce amino acid changes in the loops that enable preparation of a high diversity library that can be utilized to obtain ligands against macromolecules. We believe this is the first report of protein engineering to convert a neurotoxin to receptor ligands other than the parent receptor, the identification of an agonist from non-immunoglobulin proteins, the construction of peptide mimic of IL-6, and the successful size reduction of a single-chain protein.

  12. Interleukin-6 and C-Reactive Protein Levels and 9-Year Cognitive Decline in Community-Dwelling Older Women: The Women's Health and Aging Study II.

    Science.gov (United States)

    Palta, Priya; Xue, Qian-Li; Deal, Jennifer A; Fried, Linda P; Walston, Jeremy D; Carlson, Michelle C

    2015-07-01

    Elevated inflammation is a proposed mechanism relating chronic diseases to cognitive dysfunction. The objective of this study was to test the hypothesis that greater levels of inflammation, as measured by the proinflammatory cytokine interleukin-6 (IL-6) and C-reactive protein, are associated with faster rates of cognitive decline among cognitively intact community-dwelling older women. We analyzed 336 women from the Women's Health and Aging Study II. Cognitive assessments were performed at baseline and every 18-36 months, and included the following domains: immediate and delayed memory (Hopkins Verbal Learning Test), psychomotor speed (Trail Making Test, Part A), and executive function (Trail Making Test, Part B). Aggregate measures of IL-6 and C-reactive protein, based on the average from visits one and two, were analyzed categorically. Random effects models were employed to test the relationship between tertiles of each inflammatory marker and changes in cognitive domain scores over 9 years. Moderate and high levels of IL-6 predicted early declines in psychomotor speed by 1.0 connection/min per year. There were no differences in baseline scores or rates of change across tertiles of IL-6 in memory or executive function. No differences were observed across tertiles of C-reactive protein for all cognitive domains. Higher levels of serum IL-6 were associated with greater declines in psychomotor speed over 9 years. This finding could suggest that elevated IL-6 may result in microvascular changes that may lead to damage of myelin sheaths that line neuronal axons, leading to decreased neuron propagation and impaired processing speed; however, mechanistic studies are needed to evaluate these hypotheses. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Interleukin-6-174G/C Polymorphism Contributes to Periodontitis Susceptibility: An Updated Meta-Analysis of 21 Case-Control Studies

    Directory of Open Access Journals (Sweden)

    Junfei Zhu

    2016-01-01

    Full Text Available Introduction. Chronic Periodontitis (CP is suggested to be related to gene variations. Present study aims to quantitatively estimate the association between interleukin-6- (IL-6- 174G/C polymorphism and CP susceptibility. Materials and Methods. Pubmed, Embase, and Web of Science were searched up to May 2016. The meta-analyses were performed using STATA 12.0. Results. 21 studies were yielded. Significant associations were found under heterozygote comparison and dominant model in studies fulfilling HWE (GC versus GG: OR = 0.690, 95% CI = 0.560–0.849, P=0.000; CC + GC versus GG: OR = 0.690, 95% CI = 0.568–0.838, P<0.001; significant associations were found under heterozygote comparison and dominant model in Caucasian studies fulfilling HWE (GC versus GG: OR = 0.752, 95% CI = 0.577–0.980, P=0.035; CC + GC versus GG: OR = 0.737, 95% CI = 0.576–0.944, P=0.016; significant associations were found under allele comparison, heterozygote comparison, and dominant model in Brazilian population (C versus G: OR = 0.648, 95% CI = 0.497–0.845, P=0.001; GC versus GG: OR = 0.621, 95% CI = 0.441–0.876, P=0.007; CC + GC versus GG: OR = 0.649, 95% CI = 0.470–0.896, P=0.009. Conclusion. IL-6 174 polymorphism is associated with CP susceptibility. In Brazilian and Caucasian population, IL-6 174 GG genotype plays as a risk factor to CP.

  14. Synthesis of interleukin 6 (interferon-. beta. /sub 2//B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP

    Energy Technology Data Exchange (ETDEWEB)

    Zhange, Y.; Lin, J.X.; Vilcek, J.

    1988-05-05

    Interleukin 6 (IL-6; also referred to as interferon-..beta../sub 2/, 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1.

  15. Synthesis of interleukin 6 (interferon-β2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP

    International Nuclear Information System (INIS)

    Zhange, Y.; Lin, J.X.; Vilcek, J.

    1988-01-01

    Interleukin 6 (IL-6; also referred to as interferon-β 2 , 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1

  16. Neutrophil defensins but not interleukin-6 in vaginal fluid after preterm premature rupture of membranes predict fetal/neonatal inflammation and infant neurological impairment.

    Science.gov (United States)

    Lucovnik, Miha; Kornhauser-Cerar, Lilijana; Premru-Srsen, Tanja; Gmeiner-Stopar, Tanja; Derganc, Metka

    2011-08-01

    To determine whether neutrophil defensins (HNP1-3) and interleukin-6 (IL-6) in vaginal fluid after preterm premature rupture of membranes predict fetal inflammatory response syndrome (FIRS), neurological impairment or chorioamnionitis. Prospective study. Tertiary referral university hospital. Forty-two patients with preterm premature rupture of membranes at receiver operator characteristics analysis. Fetal inflammatory response syndrome was defined as neonatal inflammation within 72 hours postpartum. Neurological impairment was defined as motor and/or tone abnormalities at one year of corrected age. Chorioamnionitis was diagnosed histologically. Levels of HNP1-3, but not IL-6, were higher in 12 cases of FIRS (p=0.019 and p=0.256, respectively). Levels of HNP1-3, but not IL-6, were higher in 14 cases of infant death or neurological impairment (p=0.015 and p=0.100, respectively) and, when only survivors were analyzed, in nine cases of neurological impairment (p=0.030 and p=0.187, respectively). Levels of HNP1-3 and IL-6 were higher in 29 cases of chorioamnionitis (p=0.005 and p=0.003, respectively). The differences remained significant after adjustment for gestational age. Levels of HNP1-3 predicted FIRS, infant death or neurological impairment and chorioamnionitis with an area under the curve of 0.75, 0.79 and 0.78, respectively. Elevated vaginal fluid HNP1-3 and IL-6 levels are associated with histological chorioamnionitis. Elevated HNP1-3 can also identify FIRS and predict infant death or neurological impairment. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

  17. Recombinant interleukin 6 with M cell-targeting moiety produced in Lactococcus lactis IL1403 as a potent mucosal adjuvant for peroral immunization.

    Science.gov (United States)

    Li, Hui-Shan; Piao, Da-Chuan; Jiang, Tao; Bok, Jin-Duck; Cho, Chong-Su; Lee, Yoon-Seok; Kang, Sang-Kee; Choi, Yun-Jaie

    2015-04-15

    Development and application of safe and effective mucosal adjuvants are important to improve immunization efficiency in oral vaccine. Here, we report a novel mucosal adjuvant, IL-6-CKS9, a recombinant cytokine generated by conjugating an M cell-targeting peptide (CKS9) with c-terminus of the murine interleukin 6 (IL-6), which facilitated enhancement of mucosal immune response. Lactococcus lactis IL1403, a food-grade strain of lactic acid bacteria (LAB) which is widely used in dairy industry, was used as a host cell to express and secrete the IL-6-CKS9 for a mucosal vaccine adjuvant. The recombinant L. lactis IL1403 secreting IL-6-CKS9 was orally administered with a model antigen protein, M-BmpB (Brachyspira membrane protein B conjugated with CKS9), to BALB/c mice for mucosal immunization. ELISA analyses showed consistent enhancement tendencies in induction of anti-M-BmpB antibody levels both with mucosal (IgA) and systemic (IgG) immune responses in IL-6-CKS9-LAB treated group compared with other groups tested by conducting two separated mice immunization assays. In addition, we characterized that the oral administration of model protein antigen with live LAB producing IL-6-CKS9 could induce both Th1 and Th2 type immune responses by analysis of the specific anti-BmpB IgG1 and IgG2a isotypes in the sera and also investigated possible oral tolerance in our vaccine strategy. Collectively, our results showed successful production and secretion of recombinant murine IL-6 with M cell-targeting moiety (IL-6-CKS9) from L. lactis IL1403 and demonstrated the live recombinant LAB producing IL-6-CKS9 could have a potential to be used as an efficient adjuvant for peroral vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Interleukin 6-Mediated Endothelial Barrier Disturbances Can Be Attenuated by Blockade of the IL6 Receptor Expressed in Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Blecharz-Lang, Kinga G; Wagner, Josephin; Fries, Alexa; Nieminen-Kelhä, Melina; Rösner, Jörg; Schneider, Ulf C; Vajkoczy, Peter

    2018-02-10

    Compromised blood-brain barrier (BBB) by dysregulation of cellular junctions is a hallmark of many cerebrovascular disorders due to the pro-inflammatory cytokines action. Interleukin 6 (IL6) is implicated in inflammatory processes and in secondary brain injury after subarachnoid hemorrhage (SAH) but its role in the maintenance of cerebral endothelium still requires a precise elucidation. Although IL6 has been shown to exert pro-inflammatory action on brain microvascular endothelial cells (ECs), the expression of one of the IL6 receptors, the IL6R is controversially discussed. In attempt to reach more clarity in this issue, we present here an evident baseline expression of the IL6R in BBB endothelium in vivo and in an in vitro model of the BBB, the cEND cell line. A significantly increased expression of IL6R and its ligand was observed in BBB capillaries 2 days after experimental SAH in mice. In vitro, we saw IL6 administration resulting in an intracellular and extracellular elevation of IL6 protein, which was accompanied by a reduced expression of tight and adherens junctions, claudin-5, occludin, and vascular-endothelial (VE-) cadherin. By functional assays, we could demonstrate IL6-incubated brain ECs to lose their endothelial integrity that can be attenuated by inhibiting the IL6R. Blockade of the IL6R by a neutralizing antibody has reconstituted the intercellular junction expression to the control level and caused a restoration of the transendothelial electrical resistance of the cEND cell monolayer. Our findings add depth to the current understanding of the involvement of the endothelial IL6R in the loss of EC integrity implicating potential therapy options.

  19. Detection of Increased Plasma Interleukin-6 Levels and Prevalence of Prevotella copri and Bacteroides vulgatus in the Feces of Type 2 Diabetes Patients

    Science.gov (United States)

    Leite, Aline Zazeri; Rodrigues, Nathália de Campos; Gonzaga, Marina Ignácio; Paiolo, João Carlos Cicogna; de Souza, Carolina Arantes; Stefanutto, Nadine Aparecida Vicentini; Omori, Wellington Pine; Pinheiro, Daniel Guariz; Brisotti, João Luiz; Matheucci Junior, Euclides; Mariano, Vânia Sammartino; de Oliveira, Gislane Lelis Vilela

    2017-01-01

    Intestinal dysbiosis and metabolic endotoxemia have been associated with metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes (T2D). The main goal of the present study was to evaluate the intestinal dysbiosis in Brazilian T2D patients and correlate these data with inflammatory cytokines and lipopolysaccharides (LPS) plasma concentrations. This study was approved by the Ethics Committees from Barretos Cancer Hospital and all individuals signed the informed consent form. Stool samples were required for DNA extraction, and the V3/V4 regions of bacterial 16S were sequenced using an Illumina platform. Peripheral blood was used to quantify inflammatory cytokines and plasma LPS concentrations, by CBA flex and ELISA, respectively. Statistical analyses were performed using Mann–Whitney and Spearman’s tests. Analysis of variance, diversity indexes, and analysis of alpha- and beta-diversity were conducted using an annotated Operational Taxonomic Unit table. This study included 20 patients and 22 controls. We observed significant differences (P Prevotella copri, Bacteroides vulgatus, Bacteroides rodentium, and Bacteroides xylanisolvens. The proinflammatory interleukin-6 (IL-6) was significantly increased (P Prevotella species, and a positive correlation between the LPS levels and P. copri reads. The P. copri and B. vulgatus species were associated with insulin resistance in previous studies. In this study, we suggested that the prevalence of Gram-negative species in the gut and the increased plasma IL-6 in patients could be linked to low-grade inflammation and insulin resistance. In conclusion, the P. copri and B. vulgatus species could represent an intestinal microbiota signature, associated with T2D development. Furthermore, the identification of these Gram-negative bacteria, and the detection of inflammatory markers, such as increased IL-6, could be used as diabetes predictive markers in overweight, obese and in genetically predisposed

  20. Detection of Increased Plasma Interleukin-6 Levels and Prevalence ofPrevotella copriandBacteroides vulgatusin the Feces of Type 2 Diabetes Patients.

    Science.gov (United States)

    Leite, Aline Zazeri; Rodrigues, Nathália de Campos; Gonzaga, Marina Ignácio; Paiolo, João Carlos Cicogna; de Souza, Carolina Arantes; Stefanutto, Nadine Aparecida Vicentini; Omori, Wellington Pine; Pinheiro, Daniel Guariz; Brisotti, João Luiz; Matheucci Junior, Euclides; Mariano, Vânia Sammartino; de Oliveira, Gislane Lelis Vilela

    2017-01-01

    Intestinal dysbiosis and metabolic endotoxemia have been associated with metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes (T2D). The main goal of the present study was to evaluate the intestinal dysbiosis in Brazilian T2D patients and correlate these data with inflammatory cytokines and lipopolysaccharides (LPS) plasma concentrations. This study was approved by the Ethics Committees from Barretos Cancer Hospital and all individuals signed the informed consent form. Stool samples were required for DNA extraction, and the V3/V4 regions of bacterial 16S were sequenced using an Illumina platform. Peripheral blood was used to quantify inflammatory cytokines and plasma LPS concentrations, by CBA flex and ELISA, respectively. Statistical analyses were performed using Mann-Whitney and Spearman's tests. Analysis of variance, diversity indexes, and analysis of alpha- and beta-diversity were conducted using an annotated Operational Taxonomic Unit table. This study included 20 patients and 22 controls. We observed significant differences ( P  Prevotella copri, Bacteroides vulgatus, Bacteroides rodentium , and Bacteroides xylanisolvens . The proinflammatory interleukin-6 (IL-6) was significantly increased ( P  Prevotella species, and a positive correlation between the LPS levels and P. copri reads. The P. copri and B. vulgatus species were associated with insulin resistance in previous studies. In this study, we suggested that the prevalence of Gram-negative species in the gut and the increased plasma IL-6 in patients could be linked to low-grade inflammation and insulin resistance. In conclusion, the P. copri and B. vulgatus species could represent an intestinal microbiota signature, associated with T2D development. Furthermore, the identification of these Gram-negative bacteria, and the detection of inflammatory markers, such as increased IL-6, could be used as diabetes predictive markers in overweight, obese and in genetically predisposed

  1. Cisplatin treatment increases stemness through upregulation of hypoxia-inducible factors by interleukin-6 in non-small cell lung cancer.

    Science.gov (United States)

    Zhang, Fuquan; Duan, Shanzhou; Tsai, Ying; Keng, Peter C; Chen, Yongbing; Lee, Soo Ok; Chen, Yuhchyau

    2016-06-01

    Cisplatin-resistant A549 and H157 (A549CisR and H157CisR) non-small cell lung cancer cells show increased stemness of cancer stem cells (CSCs) compared to their parental cells. We investigated whether interleukin-6 (IL-6) signaling contributes to this increased stemness in cisplatin-resistant cells. When A549CisR and H157CisR cells were treated with neutralizing IL-6 antibody, decreased cisplatin resistance was observed, whereas IL-6 treatment of parental cells resulted in increased cisplatin resistance. Expression of the CSC markers was significantly upregulated in IL-6-expressing scramble cells (in vitro) and scramble cell-derived tumor tissues (in vivo) after cisplatin treatment, but not in IL-6 knocked down (IL-6si) (in vitro) cells and in IL-6si cell-derived tumor tissues (in vivo), suggesting the importance of IL-6 signaling in triggering increased stemness during cisplatin resistance development. Hypoxia inducible factors (HIFs) were upregulated by IL-6 and responsible for the increased CSC stemness on cisplatin treatment. Mechanism dissection studies found that upregulation of HIFs by IL-6 was through transcriptional control and inhibition of HIF degradation. Treatment of HIF inhibitor (FM19G11) abolished the upregulation of CSC markers and increased sphere formations in IL-6 expressing cells on cisplatin treatment. In all, IL-6-mediated HIF upregulation is important in increasing stemness during cisplatin resistance development, and we suggest that the strategies of inhibiting IL-6 signaling or its downstream HIF molecules can be used as future therapeutic approaches to target CSCs after cisplatin treatment for lung cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  2. Glutamine effects on heat shock protein 70 and interleukines 6 and 10: Randomized trial of glutamine supplementation versus standard parenteral nutrition in critically ill children.

    Science.gov (United States)

    Jordan, Iolanda; Balaguer, Mònica; Esteban, M Esther; Cambra, Francisco José; Felipe, Aida; Hernández, Lluïsa; Alsina, Laia; Molero, Marta; Villaronga, Miquel; Esteban, Elisabeth

    2016-02-01

    To determine whether glutamine (Gln) supplementation would have a role modifying both the oxidative stress and the inflammatory response of critically ill children. Prospective, randomized, double-blind, interventional clinical trial. Selection criteria were children requiring parenteral nutrition for at least 5 days diagnosed with severe sepsis or post major surgery. Patients were randomly assigned to standard parenteral nutrition (SPN, 49 subjects) or standard parenteral nutrition with glutamine supplementation (SPN + Gln, 49 subjects). Glutamine levels failed to show statistical differences between groups. At day 5, patients in the SPN + Gln group had significantly higher levels of HSP-70 (heat shock protein 70) as compared with the SPN group (68.6 vs 5.4, p = 0.014). In both groups, IL-6 (interleukine 6) levels showed a remarkable descent from baseline and day 2 (SPN: 42.24 vs 9.39, p < 0.001; SPN + Gln: 35.20 vs 13.80, p < 0.001) but only the treatment group showed a statistically significant decrease between day 2 and day 5 (13.80 vs 10.55, p = 0.013). Levels of IL-10 (interleukine 10) did not vary among visits except in the SPN between baseline and day 2 (9.55 vs 5.356, p < 0.001). At the end of the study, no significant differences between groups for PICU and hospital stay were observed. No adverse events were detected in any group. Glutamine supplementation in critically-ill children contributed to maintain high HSP-70 levels for longer. Glutamine supplementation had no influence on IL-10 and failed to show a significant reduction of IL-6 levels. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  3. Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2016-01-01

    Full Text Available The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-α and the innate immune response in vivo in a model of Streptococcus pneumoniae-induced meningitis. For the experiments IL-6−/−, TNFR1−/−, and TNFR1-IL-6−/− KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1−/−, IL-6−/−, and TNFR1-IL-6−/− mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1−/− and TNFR1-IL-6−/− mice in contrast to IL-6−/− and wild type mice. Furthermore, the increased mortality of TNFR1−/− and TNFR1-IL-6−/− mice correlated with decreased glial cell activation compared to IL-6−/− or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone.

  4. Plasma acetate, gluconate and interleukin-6 profiles during and after cardiopulmonary bypass: a comparison of Plasma-Lyte 148 with a bicarbonate-balanced solution.

    Science.gov (United States)

    Davies, Paul G; Venkatesh, Balasubramanian; Morgan, Thomas J; Presneill, Jeffrey J; Kruger, Peter S; Thomas, Bronwyn J; Roberts, Michael S; Mundy, Julie

    2011-01-01

    As even small concentrations of acetate in the plasma result in pro-inflammatory and cardiotoxic effects, it has been removed from renal replacement fluids. However, Plasma-Lyte 148 (Plasma-Lyte), an electrolyte replacement solution containing acetate plus gluconate is a common circuit prime for cardio-pulmonary bypass (CPB). No published data exist on the peak plasma acetate and gluconate concentrations resulting from the use of Plasma-Lyte 148 during CPB. Thirty adult patients were systematically allocated 1:1 to CPB prime with either bicarbonate-balanced fluid (24 mmol/L bicarbonate) or Plasma-Lyte 148. Arterial blood acetate, gluconate and interleukin-6 (IL-6) levels were measured immediately before CPB (T1), three minutes after CPB commencement (T2), immediately before CPB separation (T3), and four hours post separation (T4). Acetate concentrations (normal 0.04 to 0.07 mmol/L) became markedly elevated at T2, where the Plasma-Lyte group (median 3.69, range (2.46 to 8.55)) exceeded the bicarbonate group (0.16 (0.02 to 3.49), P Plasma-Lyte 0.35 (0.00 to 1.84) versus bicarbonate 0.17 (0.00 to 0.81)). Normal circulating acetate concentrations were not restored until T4. Similar gluconate concentration profiles and inter-group differences were seen, with a slower T3 decay. IL-6 increased across CPB, peaking at T4, with no clear difference between groups. Use of acetate containing prime solutions result in supraphysiological plasma concentrations of acetate. The use of acetate-free prime fluid in CPB significantly reduced but did not eliminate large acetate surges in cardiac surgical patients. Complete elimination of acetate surges would require the use of acetate free bolus fluids and cardioplegia solutions. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000267055.

  5. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.

    Directory of Open Access Journals (Sweden)

    John Danesh

    2008-04-01

    Full Text Available The relevance to coronary heart disease (CHD of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6, may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context.Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y. Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65 per 2 standard deviation (SD increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15 with long-term average ("usual" IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death. Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83 per 2 SD increase in baseline IL-6

  6. Long-term bicycle riding ameliorates the depression of the patients undergoing hemodialysis by affecting the levels of interleukin-6 and interleukin-18

    Directory of Open Access Journals (Sweden)

    Zhao C

    2016-12-01

    Full Text Available Chunhui Zhao, Hui Ma, Lei Yang, Yong Xiao Blood Purification Center, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China Purpose: Hemodialysis patients with depression have a higher risk of death and hospitalization. Although there is pharmacological management for the depression of hemodialysis patients, the adverse effect of the drug limits the use. The nonpharmacological way, bicycle riding, may be an effective way for the therapy of the depression in hemodialysis patients. However, the underlying mechanism of this relationship is still not fully explained, while interleukin-6 (IL-6 and interleukin-18 (IL-18 are associated with depression and exercise. Thus, the effects of bicycle riding on the levels of the interleukin were explored. Participants and methods: One hundred and eighty-nine patients with chronic hemodialysis were selected and randomly assigned to three groups of medicine (MG, received 20-mg escitalopram daily, medicine and aerobic exercise (MAG, received 20-mg escitalopram daily and bicycle riding six times weekly, and only aerobic exercise (AG, received 20-mg placebo daily and bicycle riding six times weekly. The whole experiment lasted for 18 weeks. The quality of life (36-Item Short Form Health Survey and depression severity according to criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition [DSM-IV] were measured before and at the end of this study. The serum levels of IL-6 and IL-18 were measured by an enzyme-linked immunosorbent assay kit. Results: The quality of life was improved and depression severity was reduced significantly in the MAG and AG groups when compared with the MG group (P<0.05. Serum levels of IL-6 and IL-18 were the highest in the MG group, moderate in the MAG group and the lowest in AG group. On the other hand, the serum levels of IL-6 and IL-18 were closely associated with depression scores (P<0.05. Conclusion: Aerobic exercise

  7. Long-Term Interleukin-6 Levels and Subsequent Risk of Coronary Heart Disease: Two New Prospective Studies and a Systematic Review

    Science.gov (United States)

    Mann, Andrea G; Sarwar, Nadeem; Wood, Angela; Angleman, Sara B; Wensley, Frances; Higgins, Julian P. T; Lennon, Lucy; Eiriksdottir, Gudny; Rumley, Ann; Whincup, Peter H; Lowe, Gordon D. O; Gudnason, Vilmundur

    2008-01-01

    Background The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Methods and Findings Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28–0.53, over 4 y, and 0.35, 95% CI 0.23–0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29–1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45–3.15) with long-term average (“usual”) IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42–1

  8. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

    LENUS (Irish Health Repository)

    Bull, S J

    2009-12-01

    Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King\\'s College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The \\'low IL-6\\' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The \\'high transcription\\' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the \\'protective\\' effect of the 5-HTTLPR polymorphism was evident only in the presence of the \\'low IL-6\\' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the \\'high IL-6\\' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role

  9. PRELIMINARY ANALYSIS OF INTERLEUKIN-6 CHANGES IN PRE- AND POSTOPERATIVE IN DIABETIC PATIENTS WITH BMI<35 SUBMITTED TO PARTIAL DUODENAL SWITCH.

    Science.gov (United States)

    Reis, Luciano Dias de Oliveira; Nassif, Paulo Afonso Nunes; Tabushi, Fernando Issamu; Milléo, Fábio Quirillo; Favero, Giovani Marino; Ariede, Bruno Luiz; Reis, Cassiana Franco Dias Dos; Dalabona, Bruno Franco

    2016-01-01

    Studies related to obesity have shown association with metabolic syndrome. Data showing that obesity is capable to cause low grade chronic inflammation, without its classic signs and symptoms, call attention to researches to study different cells types and the mechanism of the inflammatory process. To evaluate the variation of glycated hemoglobin (HbA1c) and the pro-inflammatory cytokine interleukin-6 (IL6) in diabetic patients with BMI de operation 39,47739±3,410057 and the HbA1c average of 10,67 and 5.8 in the same period. The partial duodenal switch was efficient to control one year after the procedure the chronic inflammatory process caused by the diabetes mellitus type 2 with BMI de promover inflamação, sem os sinais clássicos, tem levado vários grupos de pesquisa a caracterizar os tipos celulares que agem e o mecanismo envolvido neste processo. Avaliar a variação da hemoglobina glicada e a secreção da citocina inflamatória, interleucina-6, em indivíduos diabéticos com IMCde desvio duodenal parcial. Nove pacientes foram avaliados antes e um ano após a operação e a variação da concentração da interleucina-6 foi avaliada pela metodologia de Elisa. Também foi avaliada a variação da HbA1c. A quantificação de interleucina-6 apresentou no pré-operatório valor de 65,50436±2,911993 pg/ml e de 39,47739+3,410057 pg/ml após um ano da operação e a hemoglobina glicada apresentou média de 10,67 no pré-operatório e de 5,8 após um ano da operação. O desvio duodenal parcial foi capaz de, um ano após o procedimento, diminuir os efeitos da inflamação crônica demonstrada pela diminuição da concentração da interleucina-6 plasmática e normalizar a hemoglobina glicada em pacientes diabéticos com IMC<35 kg/m2.

  10. Diesel exhaust particles induced release of interleukin 6 and 8 by (primed) human bronchial epithelial cells (BEAS 2B) in vitro.

    Science.gov (United States)

    Steerenberg, P A; Zonnenberg, J A; Dormans, J A; Joon, P N; Wouters, I M; van Bree, L; Scheepers, P T; Van Loveren, H

    1998-01-01

    Several epidemiological studies have recently shown associations of increased premature mortality rates with ambient particulate air pollution. Diesel exhaust particles (DEP) may constitute an important part of (ultra)fine particulate air pollution in urban areas and may therefore contribute to its toxicity. Epithelial lining of the respiratory tract may be the first target of the toxic effects of DEP, that upon exposure may release pro-inflammatory mediators such as interleukin 6 and 8 (IL-6, IL-8), ultimately causing airway tissue damage and immune alterations. In this study the effects of in vitro DEP exposure (0.04-0.33 mg/mL) on IL-6, IL-8 production by a human bronchial epithelial cell line (BEAS-2B) were investigated. For comparison, the production of interleukins during exposure to silica and titanium oxide (TiO2) were also studied, representing relatively toxic and non-toxic particles, respectively. Scanning and transmission electron microscopy showed that the size of the DEP particles ranged between 25 to 35 nm and that DEP was phagocytized by BEAS-2B cells. An increase in IL-6 and IL-8 production (11- and 4-fold, respectively) was found after 24 or 48 h of exposure to DEP compared to the non-exposed cells. This increase was lower compared to silica (17- and 3.3-fold) and higher as compared to TiO2 which showed no increase for IL-6 and IL-8. To study the DEP effect on inflammation-primed cells, BEAS-2B cells were exposed to both tumor necrosis factor-alpha (TNF-alpha) and subsequently to DEP. Exposure to TNF-alpha caused a strong increase in IL-6 and IL-8 production. Additive effects on the IL-6 and IL-8 production by BEAS-2B cells were found after TNF-alpha priming and subsequently exposure to DEP, only at a low dose of DEP and TNF-alpha (0.05-0.2 ng/mL). In conclusion, BEAS-2B phagocytized DEP and produced an increased amount of IL-6 and IL-8. In TNF-alpha primed BEAS-2B cells, DEP increased interleukin production only at low concentrations of DEP and

  11. Keap1 silencing boosts lipopolysaccharide-induced transcription of interleukin 6 via activation of nuclear factor κB in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peng [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Xue, Peng; Dong, Jian [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Peng, Hui [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Clewell, Rebecca [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Wang, Aiping [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Wang, Yue [Institute for Medical Device Standardization Administration, National Institutes for Food and Drug Control, Beijing (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2013-11-01

    Interleukin-6 (IL6) is a multifunctional cytokine that regulates immune and inflammatory responses. Multiple transcription factors, including nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf2), regulate IL6 transcription. Kelch-like ECH-associated protein 1 (Keap1) is a substrate adaptor protein for the Cullin 3-dependent E3 ubiquitin ligase complex, which regulates the degradation of many proteins, including Nrf2 and IκB kinase β (IKKβ). Here, we found that stable knockdown of Keap1 (Keap1-KD) in RAW 264.7 (RAW) mouse macrophages and human monocyte THP-1 cells significantly increased expression of Il6, and Nrf2-target genes, under basal and lipopolysaccharide (LPS, 0.001–0.1 μg/ml)-challenged conditions. However, Nrf2 activation alone, by tert-butylhydroquinone treatment of RAW cells, did not increase expression of Il6. Compared to cells transduced with scrambled non-target negative control shRNA, Keap1-KD RAW cells showed enhanced protein levels of IKKβ and increased expression and phosphorylation of NF-κB p65 under non-stressed and LPS-treated conditions. Because the expression of Il6 in Keap1-KD RAW cells was significantly attenuated by silencing of Ikkβ, but not Nrf2, it appears that stabilized IKKβ is responsible for the enhanced transactivation of Il6 in Keap1-KD cells. This study demonstrated that silencing of Keap1 in macrophages boosts LPS-induced transcription of Il6 via NF-κB activation. Given the importance of IL6 in the inflammatory response, the Keap1–IKKβ–NF-κB pathway may be a novel target for treatment and prevention of inflammation and associated disorders. - Highlights: • Knockdown of Keap1 increases expression of Il6 in macrophages. • Silencing of Keap1 results in protein accumulation of IKKβ and NF-κB p65. • Induction of Il6 resulting from Keap1 silencing is attributed to NF-κB activation.

  12. Effect of Marine-Derived n-3 Polyunsaturated Fatty Acids on C-Reactive Protein, Interleukin 6 and Tumor Necrosis Factor α: A Meta-Analysis

    Science.gov (United States)

    Li, Kelei; Huang, Tao; Zheng, Jusheng; Wu, Kejian; Li, Duo

    2014-01-01

    Background Previous studies did not draw a consistent conclusion about the effects of marine-derived n-3 polyunsaturated fatty acids (PUFAs) on fasting blood level of C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). Methods and Findings A comprehensive search of Web of Science, PubMed, Embase and Medline (from 1950 to 2013) and bibliographies of relevant articles was undertaken. Sixty-eight RCTs with a total of 4601 subjects were included in the meta-analysis. Marine-derived n-3 PUFAs supplementation showed a lowering effect on Marine-derived n-3 PUFAs supplementation had a significant lowering effect on TNF-α, IL-6 and CRP in three groups of subjects (subjects with chronic non-autoimmune disease, subjects with chronic autoimmune disease and healthy subjects). A significant negative linear relationship between duration and effect size of marine-derived n-3 PUFAs supplementation on fasting blood levels of TNF-α and IL-6 in subjects with chronic non-autoimmune disease was observed, indicating that longer duration of supplementation could lead to a greater lowering effect. A similar linear relationship was also observed for IL-6 levels in healthy subjects. Restricted cubic spline analysis and subgroup analysis showed that the lowering effect of marine-derived n-3 PUFAs on CRP, IL-6 and TNF-α in subjects with chronic non-autoimmune disease became weakened when body mass index was greater than 30 kg/m2. The effect of marine-derived n-3 PUFAs from dietary intake was only assessed in subjects with chronic non-autoimmune disease, and a significant lowering effect was observed on IL-6, but not on CRP and TNF-α. Conclusions Marine-derived n-3 PUFAs supplementation had a significant lowering effect on CRP, IL-6 and TNF-α level. The lowering effect was most effective in non-obese subjects and consecutive long-term supplementation was recommended. PMID:24505395

  13. Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy.

    Directory of Open Access Journals (Sweden)

    Birgit Grund

    Full Text Available Despite effective antiretroviral treatment (ART, HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers, perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduction in serious non-AIDS conditions or death from any cause that might be achieved with treatments that reduce inflammation and/or coagulation, we examined associations of interleukin-6 (IL-6, D-dimer, and high-sensitivity C-reactive protein (hsCRP levels with serious non-AIDS conditions or death in 3 large cohorts.In HIV-positive adults on suppressive ART, associations of IL-6, D-dimer, and hsCRP levels at study entry with serious non-AIDS conditions or death were studied using Cox regression. Hazard ratios (HR adjusted for age, gender, study, and regression dilution bias (due to within-person biomarker variability were used to predict risk reductions in serious non-AIDS conditions or death associated with lower "usual" levels of IL-6 and D-dimer.Over 4.9 years of mean follow-up, 260 of the 3766 participants experienced serious non-AIDS conditions or death. IL-6, D-dimer and hsCRP were each individually associated with risk of serious non-AIDS conditions or death, HR = 1.45 (95% CI: 1.30 to 1.63, 1.28 (95% CI: 1.14 to 1.44, and 1.17 (95% CI: 1.09 to 1.26 per 2x higher biomarker levels, respectively. In joint models, IL-6 and D-dimer were independently associated with serious non-AIDS conditions or death, with consistent results across the 3 cohorts and across serious non-AIDS event types. The association of IL-6 and D-dimer with serious non-AIDS conditions or death was graded and persisted throughout follow-up. For 25% lower "usual" IL-6 and D-dimer levels, the joint biomarker model estimates a 37% reduction (95% CI: 28 to 46% in the risk of serious non-AIDS conditions or death if the relationship is causal.Both IL-6 and D-dimer are independently associated with

  14. INNOVATIVE TREATMENTS FOR TAKAYASU’S ARTERITIS: A FOCUS ON INTERLEUKIN-6 INHIBITORS. THE AUTHORS’ EXPERIENCE WITH TOCILIZUMAB AND A REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    T. V. Beketova

    2017-01-01

    Full Text Available The need for further improvement of treatments for Takayasu’s arteritis (TA, the progress in understanding the mechanisms of the disease, and the introduction of biological agents (BA in rheumatology practice have created preconditions for developing a new TA pharmacotherapy using BA associated with interleukin 6 (IL-6 inhibition. The authors describe their two own cases of tocilizumab (TCZ use for complicated TA. They analyze the results of TCZ treatment by the data of preliminary trials in 115 patients with TA, which have been published in 30 literature sources, as well as the results of Phase III double-blind, randomized placebo-controlled trials (RPCTs of the safety and efficacy of TCZ in 18 patients with refractory TA. In one case with a long history of complicated TA, the control of TA activity and the reduction in the dose of glucocorticoids due to TCZ use contributed to the favorable course of pregnancy and labor. In the other case with the onset of TA and focal pulmonary tuberculosis (TB treated with anti-TB drugs during TCZ monotherapy for 6 months could control TA and achieve TB cure. Preliminary trials showed that TCZ treatment-induced remission or improvement was observed in 85% of patients with TA, including that with a refractory course. RPCTs indicated that the relapse-free survival after 6-month maintenance treatment with TCZ was higher than that in the placebo group (51 and 23%, respectively; but the differences failed to reach statistical significance (p = 0.0596. Due to the fact that a recurrence of TA can occur in patients treated with TCZ, it is appropriate to combine this drug with cytostatic drugs, methotrexate in particular. The use of IL-6 inhibitors should be considered as a potentially effective and relatively safe innovative (off-label treatment for refractory TA in patients with intolerance or contraindications to standard therapy, which requires further larger randomized clinical trials. Since now

  15. Effects of diode laser (980 nm) on orthodontic tooth movement and interleukin 6 levels in gingival crevicular fluid in female subjects.

    Science.gov (United States)

    Yassaei, S; Aghili, H; Afshari, J Tavakol; Bagherpour, A; Eslami, F

    2016-12-01

    The aim of this study was to evaluate the effects of low-level laser irradiation on the rate of orthodontic tooth movement (OTM) and the interleukin-6 (IL-6) concentration in gingival crevicular fluid (GCF) during orthodontic treatment. In this randomized split-mouth double blind clinical trial, 11 female patients aged 14 to 25 years (mean 19 ± 4.21 year), who required canine retraction following four first premolars extraction, were selected. The GaAlAs laser diode laser (A.R.C. Laser GmbH, Nürnberg, Germany) (980 nm, 100 mW, 5.6 J/cm 2 , three points from the buccal side and three from lingual side of the tooth, 56 s, running in continuous mode) was used for canine retraction in only one maxillary quadrant (LG). The irradiation time for each cervical and middle third of the tooth was 10 s, and 8 s for the apical third of the tooth. The other maxillary quadrant served as the control group (CG) using the laser pseudo-application in this side. The laser irradiation was applied on days 0, 7, 14, 21, and 28 of each month during the canine retraction phase. Canine retraction was done using closed coil spring with 150 g force on rectangular wires after the alignment and leveling. This study was done in 11 months. Dental casts were made at different time points during the treatment, and the amount of tooth movement was measured. To evaluate the levels of IL-6, GCF samples were collected from the distal side of the maxillary canine teeth on both quadrants at the beginning of the trial, the end of aligning phase, and on day 21 of each month during canine retraction. Although the mean rate of canine retraction was higher in the LG (0.013) than the CG (0.012) and there was definitely a tendency for more canine retraction in the LLLI, but the results failed to show any significant difference between the mean rate of canine retraction of both groups (P = 0.068). A paired t test showed that there was no significant difference in the mean concentration of IL

  16. UMBILICAL CORD SERUM INTERLEUKIN-6, C-REACTIVE PROTEIN, AND MYELOPEROXIDASE CONCENTRATIONS AT BIRTH AND ASSOCIATION WITH NEONATAL MORBIDITIES AND LONG TERM NEURODEVELOPMENTAL OUTCOMES

    Science.gov (United States)

    Sorokin, Yoram; Romero, Roberto; Mele, Lisa; Iams, Jay D.; Peaceman, Alan M.; Leveno, Kenneth J.; Harper, Margaret; Caritis, Steve N.; Mercer, Brian M.; Thorp, John M.; O’Sullivan, Mary Jo; Ramin, Susan M.; Carpenter, Marshall W.; Rouse, Dwight J.; Sibai, Baha

    2015-01-01

    OBJECTIVE To determine if umbilical cord serum concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and myeloperoxidase (MPO), in pregnancies at risk for preterm birth (PTB), are associated with neonatal morbidities and/or altered neurodevelopmental outcomes in the children. STUDY DESIGN Umbilical cord serum samples were collected at birth from 400 newborns delivered within a multicenter randomized controlled trial of repeated versus single course of antenatal corticosteroids (ACs), in women at increased risk for PTB. Newborns were followed through discharge and were evaluated between 36 and 42 months corrected age with neurological examination and Bayley Scales of Infant Development. Umbilical cord serum concentrations of IL-6, CRP, and MPO were determined using enzyme-linked immunoassays. Multivariate logistic regression analyses explored the relationship between umbilical cord serum IL-6, CRP and MPO levels, adverse newborn outcomes and PTB umbilical cord IL-6 above the 75th percentile was associated with increased respiratory distress syndrome (RDS) and chronic lung disease (CLD), but not with necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), or neonatal sepsis; however, this association was not significant after adjusting for gestational age at delivery and treatment group. No significant associations between CRP or MPO, and RDS, CLD, NEC, sepsis or IVH were evident. Regression analysis revealed that CRP above the 75th percentile was associated with a decreased risk of CLD (O.R. 0.10, 95% C.I. 0.02–0.41). No associations between umbilical cord IL-6, CRP or MPO, and MDI Umbilical cord serum IL-6, CRP, and MPO, above the 75th percentile, were associated with more frequent PTB umbilical cord serum concentration of CRP is associated with reduced risk for CLD even after adjusting for gestational age at delivery. Occurrence of levels > 75th percentile of IL-6, CRP, and MPO in umbilical cord serum were associated with PTB umbilical

  17. Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Nirmala Chandralega Kampan

    2017-11-01

    Full Text Available BackgroundEpithelial ovarian cancer (EOC remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2, as well as pro-inflammatory factors such as interleukin 6 (IL-6 and tumor necrosis factor (TNF. IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs.MethodsAscites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control. In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2+ Tregs and TNFR2− Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC.ResultsHigh levels of immunosuppressive (sTNFR2, IL-10, and TGF-β and pro-inflammatory cytokines (IL-6 and TNF were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4+CD25hiFoxP3+ Tregs, resulting in an increased TNFR2+ Treg/effector T cell ratio. Furthermore, TNFR2+ Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2+ Treg frequency was inversely correlated with interferon-gamma (IFN-γ production by effector T cells, and was

  18. Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells.

    Science.gov (United States)

    Kampan, Nirmala Chandralega; Madondo, Mutsa Tatenda; McNally, Orla M; Stephens, Andrew N; Quinn, Michael A; Plebanski, Magdalena

    2017-01-01

    Epithelial ovarian cancer (EOC) remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs) in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2), as well as pro-inflammatory factors such as interleukin 6 (IL-6) and tumor necrosis factor (TNF). IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs. Ascites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control). In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2 + Tregs and TNFR2 - Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC. High levels of immunosuppressive (sTNFR2, IL-10, and TGF-β) and pro-inflammatory cytokines (IL-6 and TNF) were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4 + CD25 hi FoxP3 + Tregs, resulting in an increased TNFR2 + Treg/effector T cell ratio. Furthermore, TNFR2 + Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2 + Treg frequency was inversely correlated with interferon-gamma (IFN-γ) production by effector T cells, and was uniquely able to suppress TNFR2

  19. Effects of Supervised Structured Aerobic Exercise Training Program on Interleukin-6, Nitric Oxide Synthase-1, and Cyclooxygenase-2 in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Karimi, Hossein; Rehman, Syed Shakil Ur; Gillani, Syed Amir

    2017-06-01

    To determine the effects of supervised structured aerobic exercise training (SSAET) program on interleukin-6 (IL-6), nitric oxide synthase 1 (NOS-1), and cyclooxygenase-2 (COX-2) in type 2 diabetes mellitus (T2DM). Randomized controlled trial. Riphah Rehabilitation and Research Centre, Railways General Hospital, Rawalpindi, from January 2015 to June 2016. Patients of either gender of minimum one year history of T2DM ranging from 40-70 years of age were included. Those with chronic systemic diseases, history of regular exercise, smoking, and those on dietary plan were excluded. Atotal of 195 patients were screened; 120 were selected and 102 agreed to participate in the study. They were randomly placed into experimental and control groups. SSAETprogram, routine medication, and dietary plan were applied in experimental group; whereas, control group was managed with routine medication and dietary plan for 25 weeks. IL-6, NOS-1, and COX-2 were assessed at baseline and 25 weeks. SSAET program, routine medication and dietary plan showed significantly improved IL-6 (pre-mean=0.25 ±0.11ng/ml, post-mean=0.19 ±0.04 ng/ml), NOS-1 (pre-median=4.65 ng/ml, IQ range=1.04 ng/ml), (post-median=2.72 ng/ml, IQ range=1.60 ng/ml), and COX-2 (pre-mean=18.72 ±4.42 ng/ml, post-mean=15.18 ±2.63 ng/ml) in experimental group, as compared with control group managed by routine medication and dietary plan, where deterioration was noted in IL-6 (pre-mean=0.23 ±0.08 ng/ml, post-mean=0.27 ±0.08 ng/ml) and COX-2 (pre-mean=18.49 ±4.56 ng/ml, postmean=19.10 ±4.76 ng/ml), while NOS-1 slight improvement (pre-mean=4.99 ng/ml, IQ range=2.67 ng/ml), (postmean=4.56 ng/ml, IQ range=3.85 ng/ml). Statistically at the baseline the p-values were not significant (p>0.05) in both experimental and control groups for IL-6, COX-2 and NOS-1; while after 25 weeks of intervention, the experimental group showed significant improvement (p<0.05) in comparison with the control group. SSAET program, routine

  20. Detection of Increased Plasma Interleukin-6 Levels and Prevalence of Prevotella copri and Bacteroides vulgatus in the Feces of Type 2 Diabetes Patients

    Directory of Open Access Journals (Sweden)

    Aline Zazeri Leite

    2017-09-01

    Full Text Available Intestinal dysbiosis and metabolic endotoxemia have been associated with metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes (T2D. The main goal of the present study was to evaluate the intestinal dysbiosis in Brazilian T2D patients and correlate these data with inflammatory cytokines and lipopolysaccharides (LPS plasma concentrations. This study was approved by the Ethics Committees from Barretos Cancer Hospital and all individuals signed the informed consent form. Stool samples were required for DNA extraction, and the V3/V4 regions of bacterial 16S were sequenced using an Illumina platform. Peripheral blood was used to quantify inflammatory cytokines and plasma LPS concentrations, by CBA flex and ELISA, respectively. Statistical analyses were performed using Mann–Whitney and Spearman’s tests. Analysis of variance, diversity indexes, and analysis of alpha- and beta-diversity were conducted using an annotated Operational Taxonomic Unit table. This study included 20 patients and 22 controls. We observed significant differences (P < 0.01 in the microbiota composition (beta-diversity between patients and controls, suggesting intestinal dysbiosis in Brazilian T2D patients. The prevalent species found in patients’ feces were the Gram-negatives Prevotella copri, Bacteroides vulgatus, Bacteroides rodentium, and Bacteroides xylanisolvens. The proinflammatory interleukin-6 (IL-6 was significantly increased (P < 0.05 in patients’ plasma and LPS levels were decreased. We find correlations between the proinflammatory interferon-gamma with Gram-negatives Bacteroides and Prevotella species, and a positive correlation between the LPS levels and P. copri reads. The P. copri and B. vulgatus species were associated with insulin resistance in previous studies. In this study, we suggested that the prevalence of Gram-negative species in the gut and the increased plasma IL-6 in patients could be linked to low

  1. Phase I study of bryostatin 1: assessment of interleukin 6 and tumor necrosis factor alpha induction in vivo. The Cancer Research Campaign Phase I Committee.

    Science.gov (United States)

    Philip, P A; Rea, D; Thavasu, P; Carmichael, J; Stuart, N S; Rockett, H; Talbot, D C; Ganesan, T; Pettit, G R; Balkwill, F

    1993-11-17

    Many oncogenes have been shown to code for growth factor receptors that are involved in regulation of cell growth and proliferation and can activate transcription via protein kinase C. Bryostatin 1, a partial agonist of protein kinase C, has demonstrated potent antitumor activity in vitro and in vivo in human tumor xenografts. The aim of this phase I study was to determine the optimal dosage and toxicity profile of bryostatin 1 and its influence on cytokine release in vivo. Three successive cohorts consisting of 35 patients with various malignant tumors were treated with bryostatin 1 by intravenous infusion over 1 hour as follows: cohort A--35 micrograms/m2 (three patients) or 50 micrograms/m2 (eight patients) once every 2 weeks; cohort B--25 micrograms/m2 once a week (eight patients); and cohort C--25 micrograms/m2 once a week for 3 weeks, with no treatment during the 4th week (16 patients). Plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) were measured by immunoradiometric assay and by radioimmunoassay, respectively. The dose-limiting toxicity was grade 3 or 4 myalgia in four of 11 patients in cohort A, in two of eight in cohort B, and in none of 16 in cohort C. Occurrence of myalgia was dose related. There was no significant myelosuppression, apart from a small and transient fall in platelet count. Six patients experienced acute but transient skin flushing, dyspnea, hypotension, and bradycardia, probably related to the bryostatin 1 vehicle. TNF-alpha and IL-6 were detected in plasma at 2 and 24 hours after treatment, respectively, and the levels were dose related (P = .02). Two patients with metastatic malignant melanoma had partial remission after three or four cycles of therapy; remission lasted 6 weeks and 10+ months, respectively. The dose-limiting toxicity of bryostatin 1 was myalgia. Plasma IL-6 and TNF-alpha concentrations were increased within 24 hours of therapy. Antitumor activity against malignant melanoma was observed

  2. Neuroprotection by inhibiting the c-Jun N-terminal kinase pathway after cerebral ischemia occurs independently of interleukin-6 and keratinocyte-derived chemokine (KC/CXCL1 secretion

    Directory of Open Access Journals (Sweden)

    Benakis Corinne

    2012-04-01

    Full Text Available Abstract Background Cerebral ischemia is associated with the activation of glial cells, infiltration of leukocytes and an increase in inflammatory mediators in the ischemic brain and systemic circulation. How this inflammatory response influences lesion size and neurological outcome remains unclear. D-JNKI1, an inhibitor of the c-Jun N-terminal kinase pathway, is strongly neuroprotective in animal models of stroke. Intriguingly, the protection mediated by D-JNKI1 is high even with intravenous administration at very low doses with undetectable drug levels in the brain, pointing to a systemic mode of action, perhaps on inflammation. Findings We evaluated whether D-JNKI1, administered intravenously 3 h after the onset of middle cerebral artery occlusion (MCAO, modulates secretion of the inflammatory mediators interleukin-6 and keratinocyte-derived chemokine in the plasma and from the spleen and brain at several time points after MCAO. We found an early release of both mediators in the systemic circulation followed by an increase in the brain and went on to show a later systemic increase in vehicle-treated mice. Release of interleukin-6 and keratinocyte-derived chemokine from the spleen of mice with MCAO was not significantly different from sham mice. Interestingly, the secretion of these inflammatory mediators was not altered in the systemic circulation or brain after successful neuroprotection with D-JNKI1. Conclusions We demonstrate that neuroprotection with D-JNKI1 after experimental cerebral ischemia is independent of systemic and brain release of interleukin-6 and keratinocyte-derived chemokine. Furthermore, our findings suggest that the early systemic release of interleukin-6 and keratinocyte-derived chemokine may not necessarily predict an unfavorable outcome in this model.

  3. Prognostic Value And Daily Trend Of Interleukin-6, Neutrophil CD64 Expression, C-Reactive Protein And Lipopolysaccharide-Binding Protein In Critically Ill Patients: Reliable Predictors Of Outcome Or Not?

    Directory of Open Access Journals (Sweden)

    Djordjevic Dragan

    2015-10-01

    Full Text Available Background: Severe sepsis and/or trauma complicated by multiple organ dysfunction syndrome are the leading causes of death in critically ill patients. The aim of this prospective single-centre study was to assess the prognostic value and daily trend of interleukin-6 (IL-6, neutrophil CD64 expression, C-reactive protein (CRP and lipopolysaccharide-binding protein (LBP regarding outcome in critically ill patients with severe trauma and/or severe sepsis. Outcome measure was hospital mortality.

  4. Human Herpesvirus 8 Interleukin-6 Contributes to Primary Effusion Lymphoma Cell Viability via Suppression of Proapoptotic Cathepsin D, a Cointeraction Partner of Vitamin K Epoxide Reductase Complex Subunit 1 Variant 2

    OpenAIRE

    Chen, Daming; Gao, Yang; Nicholas, John

    2014-01-01

    Human herpesvirus 8 (HHV-8) interleukin-6 (vIL-6) promotes cell proliferation and survival and is proangiogenic, implicating it as a contributor to virus-associated Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. Although predominantly lytically expressed, vIL-6 is also produced at low, functional levels during latency in PEL cells. Unlike other IL-6 cytokines, vIL-6 is secreted very inefficiently and localizes in the endoplasmic reticulum (ER). ER-loc...

  5. Effect of supervised structured aerobic exercise training program of interleukin-6, nitric oxide synthase-1, and cyclooxygenase-2 in type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Karimi, H.; Gillani, S.A.; Rehman, S.S.U.

    2017-01-01

    To determine the effects of supervised structured aerobic exercise training (SSAET) program on interleukin-6 (IL-6), nitric oxide synthase 1 (NOS-1), and cyclooxygenase-2 (COX-2) in type 2 diabetes mellitus (T2DM). Study Design: Randomized controlled trial. Place and Duration of Study: Riphah Rehabilitation and Research Centre, Railways General Hospital, Rawalpindi, from January 2015 to June 2016. Methodology: Patients of either gender of minimum one year history of T2DM ranging from 40-70 years of age were included. Those with chronic systemic diseases, history of regular exercise, smoking, and those on dietary plan were excluded. A total of 195 patients were screened; 120 were selected and 102 agreed to participate in the study. They were randomly placed into experimental and control groups. SSAET program, routine medication, and dietary plan were applied in experimental group; whereas, control group was managed with routine medication and dietary plan for 25 weeks. IL-6, NOS-1, and COX-2 were assessed at baseline and 25 weeks. Results: SSAET program, routine medication and dietary plan showed significantly improved IL-6 (pre-mean=0.25 +-0.11ng/ml, post-mean=0.19 +-0.04 ng/ml), NOS-1 (pre-median=4.65 ng/ml, IQ range=1.04 ng/ml), (post-median=2.72 ng/ml, IQ range=1.60 ng/ml), and COX-2 (pre-mean=18.72 +-4.42 ng/ml, post-mean=15.18 +-2.63 ng/ml) in experimental group, as compared with control group managed by routine medication and dietary plan, where deterioration was noted in IL-6 (pre-mean=0.23 +-0.08 ng/ml, post-mean=0.27 +-0.08 ng/ml) and COX-2 (pre-mean=18.49 +-4.56 ng/ml, post-mean=19.10 +-4.76 ng/ml), while NOS-1 slight improvement (pre-mean=4.99 ng/ml, IQ range=2.67 ng/ml), (post-mean=4.56 ng/ml, IQ range=3.85 ng/ml). Statistically at the baseline the p-values were not significant (p>0.05) in both experimental and control groups for IL-6, COX-2 and NOS-1; while after 25 weeks of intervention, the experimental group showed significant improvement (p<0

  6. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Hetland, Merete Lund; Sørensen, Inge Juul

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated...... changes of plasma IL-6, VEGF, YKL-40, MMP-3, and total aggrecan and a potential value for monitoring disease activity and treatment response in SpA patients. Larger prospective studies are required to clarify clinical utility of these biomarkers....

  7. Interleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic Lupus Erythematosus-Like Disease of BXSB.Yaa Mice.

    Directory of Open Access Journals (Sweden)

    Shweta Jain

    Full Text Available IL6 is a multifunctional cytokine that drives terminal B cell differentiation and secretion of immunoglobulins. IL6 also cooperates with IL21 to promote differentiation of CD4+ T follicular helper cells (TFH. Elevated serum levels of IL6 correlate with disease flares in patients with systemic lupus erythematosus (SLE. We previously reported that IL21 produced by TFH plays a critical role in the development of the SLE-like disease of BXSB.Yaa mice. To examine the possible contributions of IL6 to disease, we compared disease parameters in IL6-deficient and IL6-competent BXSB.Yaa mice. We report that survival of IL6-deficient BXSB.Yaa mice was significantly prolonged in association with significant reductions in a variety of autoimmune manifestations. Moreover, B cells stimulated by co-engagement of TLR7 and B cell receptor (BCR produced high levels of IL6 that was further augmented by stimulation with Type I interferon (IFN1. Importantly, the frequencies of TFH and serum levels of IL21 were significantly reduced in IL6-deficient mice. These findings suggest that high-level production of IL6 by B cells induced by integrated signaling from the IFN1 receptor, TLR7 and BCR promotes the differentiation of IL21-secreting TFH in a signaling sequence that drives the lethal autoimmune disease of BXSB.Yaa mice.

  8. Blood Levels of S-100 Calcium-Binding Protein B, High-Sensitivity C-Reactive Protein, and Interleukin-6 for Changes in Depressive Symptom Severity after Coronary Artery Bypass Grafting: Prospective Cohort Nested within a Randomized, Controlled Trial

    Science.gov (United States)

    Pearlman, Daniel M.; Brown, Jeremiah R.; MacKenzie, Todd A.; Hernandez, Felix; Najjar, Souhel

    2014-01-01

    Background Cross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium-binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge. Methods Fifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and six-month follow-up using the Beck Depression Inventory II (BDI-II). The primary outcome of the present biomarker study was acute change in depressive symptom severity, defined as the intra-subject difference between baseline and discharge BDI-II scores. Blood biomarker levels were determined at baseline and 2 days postoperative. Results Changes in S-100B levels correlated positively with acute changes in depressive symptom severity (Spearman ρ, 0.62; P = 0.0004) and accounted for about one-fourth of their observed variance (R2, 0.23; P = 0.0105). This association remained statistically significant after adjusting for baseline S-100B levels, age, weight, body-mass index, or β-blocker use, but not baseline BDI-II scores (P = 0.064). There was no statistically significant association between the primary outcome and baseline S-100B levels, baseline high-sensitivity C-reactive protein or interleukin-6 levels, or changes in high-sensitivity C-reactive protein or interleukin-6 levels. Among most participants, levels of all three biomarkers were normal at baseline and markedly elevated at 2 days postoperative. Conclusions Acute changes in depressive symptom severity were specifically

  9. Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome

    Directory of Open Access Journals (Sweden)

    del Zoppo Gregory J

    2004-01-01

    Full Text Available Abstract Background Cerebral ischaemia initiates an inflammatory response in the brain and periphery. We assessed the relationship between peak values of plasma interleukin-6 (IL-6 in the first week after ischaemic stroke, with measures of stroke severity and outcome. Methods Thirty-seven patients with ischaemic stroke were prospectively recruited. Plasma IL-6, and other markers of peripheral inflammation, were measured at pre-determined timepoints in the first week after stroke onset. Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score (mRS at 3 months and computed tomography (CT brain infarct volume. Results Peak plasma IL-6 concentration correlated significantly (p Conclusions These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke, and clinical outcome.

  10. Circulating serum interleukin-6, serum chitinase-3-like protein-1, and plasma vascular endothelial growth factor are not predictive for remission and radiographic progression in patients with early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Brahe, C H; Dehlendorff, C; Østergaard, M

    2018-01-01

    OBJECTIVE: To investigate serum interleukin-6 (IL-6), serum chitinase-3-like protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as measures of disease activity and predictors of clinical remission and radiographic progression in two early rheumatoid arthritis (RA) randomized...... obtained at baseline and during follow-up. Serum IL-6, serum YKL-40, and plasma VEGF were measured in baseline blood samples and during follow-up. Hypotheses regarding the biomarkers' relation with DAS28 and ability to predict clinical remission (DAS28 progression (change in total.......01) and these results were confirmed in OPERA patients (r = 0.52, p progression at 2 or 5 years in either study. CONCLUSION: Serum IL-6, serum YKL-40...

  11. Early interleukin-6 enhances hepatic ketogenesis in APPSWE/PSEN1dE9 mice via 3-hydroxy-3-methylglutary-CoA synthase 2 signaling activation by p38/nuclear factor κB p65.

    Science.gov (United States)

    Shi, Le; Zhao, Daina; Hou, Chen; Peng, Yunhua; Liu, Jing; Zhang, Shuangxi; Liu, Jiankang; Long, Jiangang

    2017-08-01

    Alzheimer's disease (AD) is considered a multifactorial disease that affects the central nervous system and periphery. A decline in brain glucose metabolism is an early feature of AD and is accompanied by a phenotypic shift from aerobic glycolysis to ketogenesis. The liver is responsible for the generation of the ketone body. However, the mechanism that underlies hepatic ketogenesis in AD remains unclear. Here, we investigated hepatic ketogenesis during the early stage of AD pathogenesis in amyloid precursor protein (APP SWE ) and presenilin (PSEN1dE9) (APP/PS1) mice. We observed that β-hydroxybutyric acid was increased in the brain of the postmortem mild cognitive impairment and AD subjects and in 3-month-old APP/PS1 AD mice. A rise in 3-hydroxy-3-methylglutary-CoA synthase 2 (HMGCS2), a key enzyme for catalyzing β-hydroxybutyric acid production, was observed in early AD mice. We further showed that proinflammatory cytokines were activated in the liver prior to their activation in the brain of 3-month-old APP/PS1 mice. Among the cytokines, interleukin-6 significantly activated HMGCS2 through the binding of nuclear factor κB (NF-κB) p65 to the HMGCS2 promoter. Additionally, interleukin-6 stimulated phosphorylation of p38 mitogen activated protein kinases, an upstream molecule for NF-κB p65 signaling. We have demonstrated that a hepatic inflammatory factor enhances ketogenesis through HMGCS2 signaling activation by p38/NF-κB p65. These results provide a novel peripheral metabolic mechanism for enhanced ketone production and suggest a plausible early AD phenotype to diagnose AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

    Science.gov (United States)

    Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema

    2015-05-10

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity.

  13. Mesenchymal Stromal Cell-Derived Interleukin-6 Promotes Epithelial-Mesenchymal Transition and Acquisition of Epithelial Stem-Like Cell Properties in Ameloblastoma Epithelial Cells.

    Science.gov (United States)

    Jiang, Chunmiao; Zhang, Qunzhou; Shanti, Rabie M; Shi, Shihong; Chang, Ting-Han; Carrasco, Lee; Alawi, Faizan; Le, Anh D

    2017-09-01

    Epithelial-mesenchymal transition (EMT), a biological process associated with cancer stem-like or cancer-initiating cell formation, contributes to the invasiveness, metastasis, drug resistance, and recurrence of the malignant tumors; it remains to be determined whether similar processes contribute to the pathogenesis and progression of ameloblastoma (AM), a benign but locally invasive odontogenic neoplasm. Here, we demonstrated that EMT- and stem cell-related genes were expressed in the epithelial islands of the most common histologic variant subtype, the follicular AM. Our results revealed elevated interleukin (IL)-6 signals that were differentially expressed in the stromal compartment of the follicular AM. To explore the stromal effect on tumor pathogenesis, we isolated and characterized both mesenchymal stromal cells (AM-MSCs) and epithelial cells (AM-EpiCs) from follicular AM and demonstrated that, in in vitro culture, AM-MSCs secreted a significantly higher level of IL-6 as compared to the counterpart AM-EpiCs. Furthermore, both in vitro and in vivo studies revealed that exogenous and AM-MSC-derived IL-6 induced the expression of EMT- and stem cell-related genes in AM-EpiCs, whereas such effects were significantly abrogated either by a specific inhibitor of STAT3 or ERK1/2, or by knockdown of Slug gene expression. These findings suggest that AM-MSC-derived IL-6 promotes tumor-stem like cell formation by inducing EMT process in AM-EpiCs through STAT3 and ERK1/2-mediated signaling pathways, implying a role in the etiology and progression of the benign but locally invasive neoplasm. Stem Cells 2017;35:2083-2094. © 2017 AlphaMed Press.

  14. Contrasting effects of an ultraviolet B and an ultraviolet A tanning lamp on interleukin-6, tumour necrosis factor-alpha and intercellular adhesion molecule-1 expression.

    Science.gov (United States)

    Clingen, P H; Berneburg, M; Petit-Frère, C; Woollons, A; Lowe, J E; Arlett, C F; Green, M H

    2001-07-01

    Recent studies have demonstrated that a tanning lamp emitting predominantly ultraviolet (UV) A induces significant yields of the type of potentially mutagenic DNA damage that are associated with the onset of skin cancer (i.e. cyclobutane pyrimidine dimers). UV-induced immunosuppression is also an important event leading to skin cancer. To the modulation of key immunological molecules following exposure to a broad-spectrum UVB lamp and a predominantly UVA-emitting tanning lamp using model in vitro systems. We compared secretion and mRNA expression of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha in normal human epidermal keratinocytes, and interferon (IFN)-gamma-induced intracellular adhesion molecule (ICAM)-1 in normal human fibroblasts irradiated in vitro with a broad-spectrum UVB lamp or with a Philips 'Performance' tanning lamp. With broad-spectrum UVB irradiation, upregulation of IL-6 and TNF-alpha mRNA was detected 6 h after irradiation, and a dose-dependent increase of cytokines in the supernatants of irradiated cells was found 24 h after irradiation. In contrast, there was no cytokine secretion and little evidence for mRNA upregulation following exposure to a tanning lamp. When cells were exposed first to broad-spectrum UVB, then the tanning lamp, UVB-induced cytokine secretion was inhibited, although mRNA levels were upregulated to a level close to that observed with UVB alone. By using a Schott WG 320 nm filter to attenuate the level of UVB relative to UVA emitted by the tanning lamp, the inhibition of cytokine secretion was shown to be associated with UVA exposure. Both UV sources inhibited IFN-gamma-induced ICAM-1 mRNA expression in a dose-dependent fashion. By using a Schott WG 335 nm filter, inhibition of ICAM-1 mRNA expression by the tanning lamp was shown to be associated with UVB exposure. These results suggest that UV sources emitting different levels of UVA and UVB have differential effects on the modulation of different

  15. and interleukin-6 (-174G/C)

    African Journals Online (AJOL)

    Mona Hussein Kandil

    2013-05-26

    May 26, 2013 ... Abstract In end stage renal disease, inflammation is considered a critical regulator of atheroscle- rotic plaque formation and progression, to which many dialysis and non-dialysis-related factors may contribute. Since circulating inflammatory cytokine levels vary inter-individually, one may speculate that ...

  16. Interleukin-6 myokine signaling in skeletal muscle

    DEFF Research Database (Denmark)

    Muñoz-Cánoves, Pura; Scheele, Camilla; Pedersen, Bente K

    2013-01-01

    Interleukin (IL)-6 is a cytokine with pleiotropic functions in different tissues and organs. Skeletal muscle produces and releases significant levels of IL-6 after prolonged exercise and is therefore considered as a myokine. Muscle is also an important target of the cytokine. IL-6 signaling has...

  17. Cytokine gene polymorphism (interleukin-1β +3954, Interleukin-6 [-597/-174] and tumor necrosis factor-α -308) in chronic periodontitis with and without type 2 diabetes mellitus.

    Science.gov (United States)

    Sharma, Nitin; Joseph, Rosamma; Arun, R; Chandni, R; Srinivas, K Lekshmy; Banerjee, Moinak

    2014-01-01

    Pro-inflammatory cytokine gene polymorphisms are potential candidates for susceptibility for both type 2 diabetes mellitus (DM) and chronic periodontitis (CHP). This study explored the association of interleukin-1 beta (IL-1 β) +3954, interleukin-6 (IL-6) -597/-174 and tumor necrosis factor-alpha (TNF-α) -308 single nucleotide polymorphisms in CHP with and without type 2 DM in Malayalam speaking subjects of Dravidian ethnicity. This case control study consisted of 51 chronic periodontitis with type 2 diabetes mellitus (CHPDM) and 51 CHP patients as cases and 51 healthy subjects as controls. Polymorphisms were identified by polymerase chain reaction amplification followed by restriction enzyme digestion and gel electrophoresis. IL-1 β (+3954) TT genotype and T allele were significantly associated with CHPDM group when compared with CHP (P = 0.001), whereas CC genotype and allele C was higher in CHP subjects (P = 0.001). For IL-6 (-597) frequency of genotype GA/AA (P = 0.04) and allele A (P = 0.01) was lower in CHPDM group, and for TNF-α -308 the frequency of genotype GA (P = 0.01) and allele A (P = 0.01) was higher in CHP subjects when compared with controls. In Malayalam speaking Dravidian population, IL-6 (-597) genotype GA/AA and allele A appears to be protective for CHP with type 2 DM. Allele C of IL-1 β +3954 and allele A of TNF-α -308 appears to be risk factors for CHP individuals.

  18. Effect of low-level laser therapy on the release of interleukin-6 and basic fibroblast growth factor from cultured human skin fibroblasts in normal and high glucose mediums.

    Science.gov (United States)

    Esmaeelinejad, Mohammad; Bayat, Mohammad

    2013-12-01

    This study evaluated the effects of low-level laser therapy (LLLT) on human skin fibroblasts (HSFs) that have been cultured in high glucose concentration media. HSFs were cultured under physiological glucose condition medium, and then cultured in high glucose concentration medium (15 mM/L) for 1 or 2 weeks prior to LLLT. Experimental HSFs were irradiated with three energy densities (0.5, 1, and 2 J/cm(2)) once daily for three consecutive days. Release of interleukin-6 (IL-6) and basic fibroblast growth factor (bFGF) was evaluated using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis showed three doses of 0.5 (p = 0.049), 1 (p = 0.027), and 2 J/cm(2) (p = 0.004) stimulated the release of IL-6 in HSFs cultured in high glucose concentration medium compared with that of non-irradiated HSFs that were cultured in the same medium. LLLT with 2 J/cm(2) induced the release of bFGF from HSFs cultured in high glucose concentration medium for 1 or 2 weeks (both p = 0.04). Our study showed that LLLT stimulated the release of IL-6 and bFGF from HSFs cultured in high glucose concentration medium. LLLT was more effective in releasing IL-6 and bFGF while HSFs which were cultured in physiologic glucose concentration medium during laser irradiation.

  19. Helicobacter pylori neutrophil-activating protein induces release of histamine and interleukin-6 through G protein-mediated MAPKs and PI3K/Akt pathways in HMC-1 cells.

    Science.gov (United States)

    Tsai, Chung-Che; Kuo, Ting-Yu; Hong, Zhi-Wei; Yeh, Ying-Chieh; Shih, Kuo-Shun; Du, Shin-Yi; Fu, Hua-Wen

    2015-01-01

    Helicobacter pylori neutrophil-activating protein (HP-NAP) activates several innate leukocytes including neutrophils, monocytes, and mast cells. It has been reported that HP-NAP induces degranulation and interleukin-6 (IL-6) secretion of rat peritoneal mast cells. However, the molecular mechanism is not very clear. Here, we show that HP-NAP activates human mast cell line-1 (HMC-1) cells to secrete histamine and IL-6. The secretion depends on pertussis toxin (PTX)-sensitive heterotrimeric G proteins but not on Toll-like receptor 2. Moreover, HP-NAP induces PTX-sensitive G protein-mediated activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38-mitogen-activated protein kinase (p38 MAPK), and Akt in HMC-1 cells. Inhibition of ERK1/2, p38 MAPK, or phosphatidylinositol 3-kinase (PI3K) suppresses HP-NAP-induced release of histamine and IL-6 from HMC-1 cells. Thus, the activation of HMC-1 cells by HP-NAP is through Gi-linked G protein-coupled receptor-mediated MAPKs and PI3K/Akt pathways.

  20. Initial response of human bone marrow–derived stem cells after contact with ultrahigh-molecular-weight polyethylene (UHMWPE material: An in vitro study on cell viability and interleukin-6 expression

    Directory of Open Access Journals (Sweden)

    Iwan B Anwar

    2018-01-01

    Full Text Available Introduction: Ultrahigh-molecular-weight polyethylene (UHMWPE is a thermoplastic polymer useful in biomaterial applications, especially in orthopedic field. Yet, little is known concerning its initial effect on human bone marrow stem cells (hBMSCs after implantation. Materials and Methods: A cytotoxicity analysis was performed with a 3-(4,5-dimethylthiazol 2-yl-2,5-diphenyltetrazolium assay after 24, 48, and 72h of incubation of hBMSC culture. Expression of interleukin-6 (IL-6 was measured using enzyme-linked immunosorbent assay. Cell viability was measured with Inhibitory concentration 50% (IC50 formula. Results: All treatment groups showed a cell viability of >50% ranging from 78% to >100%. Lower expression of IL-6 of hBMSC compared to control group was found in 48h of incubation period. Conclusion: hBMSC showed high cell viability after initial contact with UHMWPE material. Modulation of IL-6 expression was present at the initial stage as a response to foreign material.

  1. Influence of a chinese traditional medicine recipes for replenishing kidney function and activating blood circulation on levels of serum with interleukin-6 and other hormones affecting calcium metabolism in female rats after ovariectomy

    International Nuclear Information System (INIS)

    Chen Zhixi; Liu Qingsi; Wei Hewei; Zhuang Hong; Chen Jinyan; Li Zhiqiang

    2001-01-01

    Objective: To investigate the influence of a Chinese traditional medicine recipe for replenishing kidney function and activating blood circulation (CRRK) in female rats on serum levels of interleukin-6 (IL-6) and other hormones affecting calcium metabolism after ovariectomy. Methods: Ninety female SD rats were divided into 6 groups: control, model (ovariectomy only) treated with nyl-estriol, treated with CRRK (high, moderate and low doses). CRRK (Gu Kang) was administered at the three dose levels for 90 days. Radioimmunoassay was used to determine the serum levels of estradiol (E 2 ), IL-6, calcitonin (CT) and BGP. The weight and histo-morphology of the uterus of the rats sacrificed after 90 days of treatment was also studied. Results: Compared with the control group, the levels of IL-6 in the model group were significantly higher (P 2 and CT, BGP were significantly lower (P 2 and BGP were significantly higher (P < 0.05-0.001). The weight of uterus was also increased (P < 0.05). The composite recipe proved to have definite effects on normalizing the uterine histomorphology. Conclusion: The results had showed that the composite recipe had good effects on prevention and therapy of osteoporosis after ovariectomy in rats

  2. Valor pronóstico y discriminatorio de la interleucina-6 y la proteína C-reactiva en la meningitis Interleukin-6 and C-reactive protein and its prognosis and differentiation value in meningitis

    OpenAIRE

    Amauri Noda Albelo; Manuel Araña Rosains; Arturo Vidal Tallet; Xiomara Casal Menéndez

    2009-01-01

    INTRODUCCIÓN. La meningitis se caracteriza por una marcada respuesta inflamatoria en el espacio subaracnoideo, que se acompaña de la producción intratecal de múltiples mediadores entre los que se hallan citocinas como el factor de necrosis tumoral alfa, la interleucina-1-beta y la interleucina-6. El objetivo del presente estudio fue estimar la concentración de interleucina-6 (IL-6) y proteína C-reactiva en el líquido cefalorraquídeo y el suero de pacientes con meningitis; determinar la posibl...

  3. Concentrations of the acute phase reactants high-sensitive C-reactive protein and YKL-40 and of interleukin-6 before and after treatment in patients with acromegaly and growth hormone deficiency.

    Science.gov (United States)

    Andreassen, Mikkel; Vestergaard, Henrik; Kristensen, Lars Østergaard

    2007-12-01

    Acromegaly is accompanied by increased cardiovascular mortality and a cluster of proatherogenic risk factors. In the general population, ischaemic heart disease (IHD) is associated with elevated levels of inflammatory markers. The acute phase reactant (APR) C-reactive protein (CRP) has been reported to be reduced in acromegaly and increase after treatment, suggesting that excess of GH/IGF-I could have anti-inflammatory effects. This is in accordance with results obtained in patients with growth hormone deficiency (GHD), where increased levels of CRP have been reported. To investigate the hypothesis that the GH/IGF-I system is a suppressive regulator of inflammatory processes. Twenty-one acromegalic patients and 19 GH-deficient patients were studied. The two APRs CRP and YKL-40 and the proinflammatory cytokine interleukin-6 (IL-6) were measured before and after treatment and in healthy matched controls. In acromegalic patients, serum concentrations of high-sensitive CRP (hsCRP) and YKL-40 were reduced compared to controls (P < 0.001) and increased (P < 0.001) after treatment, together with IL-6 (P = 0.021), to levels comparable with controls. Pretreatment serum YKL-40 and IL-6 showed a significant inverse correlation with IGF-I and GH. In GH-deficient patients, hsCRP and YKL-40 were elevated compared to controls (P = 0.001 and P = 0.048). During treatment, levels of both APRs showed a trend towards a decrease (P = 0.087 and P = 0.060), and after treatment, levels of YKL-40 no longer differed from that of controls. Serum IL-6 was not different from controls and did not change during GH treatment. The results point to the possibility of a relationship between GH disturbances and inflammatory processes.

  4. Normal Ranges for Acute Phase Reactants (Interleukin-6, Tumour Necrosis Factor-alpha and C-reactive Protein) in Umbilical Cord Blood of Healthy Term Neonates at the Mount Hope Women's Hospital, Trinidad.

    Science.gov (United States)

    Khan, A; Ali, Z

    2014-09-01

    To determine normal ranges for interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) in umbilical cord blood from healthy term neonates at the Mount Hope Women's Hospital (MHWH), Trinidad. A prospective cohort study was conducted on healthy pregnant women admitted to the MHWH during the period October 1 to December 31, 2010. Women who were term with no signs of or risk factors for sepsis were recruited into the study after informed consent was obtained. Data were collected including maternal age, antenatal and perinatal history. Umbilical cord blood samples were collected and analysed for IL-6, TNF-α and CRP. Ethical approval was obtained from the Ethics Committee, Faculty of Medical Sciences, The University of the West Indies, Trinidad and Tobago. One hundred and sixty-two samples from healthy term neonates were analysed for IL-6 and TNF-α. One hundred and thirty-one samples were analysed for CRP due to one faulty kit. There were almost equal numbers of males (55%) and females (45%). Ninety per cent were > 2500 g at birth and 10% had low birthweight. Reference ranges of 0-16.4 pg/ml, 0-29.4 pg/ml and 0-12.4 mg/L were found for IL-6, TNF-α and CRP, respectively with 95% confidence intervals (11.6, 21.5 pg/ml; 24.0, 33.1 and 8.4, 15.1, respectively). The normal ranges for IL-6, TNF-α and CRP in umbilical cord blood for healthy term Trinidadian neonates were 0-16.4 pg/ml, 0-29.4 pg/ml and 0-12.4 mg/L, respectively.

  5. The membrane-type estrogen receptor G-protein-coupled estrogen receptor suppresses lipopolysaccharide-induced interleukin 6 via inhibition of nuclear factor-kappa B pathway in murine macrophage cells.

    Science.gov (United States)

    Okamoto, Mariko; Suzuki, Takuto; Mizukami, Yoichi; Ikeda, Teruo

    2017-11-01

    The female sex hormone estrogen exerts anti-inflammatory effects. The G-protein-coupled estrogen receptor (GPER) has been recently identified as a novel membrane-type estrogen receptor that can mediate non-genomic estrogenic effects on many cell types. We previously demonstrated that GPER inhibits tumor necrosis factor alpha-induced expression of interleukin 6 (IL-6) through repression of nuclear factor-kappa B (NF-κB) promoter activity using human breast cancer cells. Although several reports have indicated that GPER suppresses Toll-like receptor-induced inflammatory cytokine expression in macrophages, the molecular mechanisms of the inhibition of cytokine production via GPER remain poorly understood. In the present study, we examined GPER-mediated inhibition of IL-6 expression induced by lipopolysaccharide (LPS) stimulation in a mouse macrophage cell line. We found that the GPER agonist G-1 inhibited LPS-induced IL-6 expression in macrophage cells, and this inhibition was due to the repression of NF-κB promoter activity by GPER. G-1 treatment also decreased the phosphorylation of inhibitor of κB kinases. Among the mitogen-activated protein kinases, the phosphorylation of c-jun N-terminal kinase (JNK) was increased by G-1. These findings delineate the novel mechanism of the inhibition of LPS-induced IL-6 through GPER-activated JNK-mediated negative regulation of the NF-κB pathway in murine macrophage cells, which links anti-inflammatory effects to estrogen. © 2017 Japanese Society of Animal Science.

  6. A Novel Mechanism by Which SDF-1β Protects Cardiac Cells From Palmitate-Induced Endoplasmic Reticulum Stress and Apoptosis via CXCR7 and AMPK/p38 MAPK-Mediated Interleukin-6 Generation

    Science.gov (United States)

    Zhao, Yuguang; Tan, Yi; Xi, Shugang; Li, Yunqian; Li, Cai; Cui, Jiuwei; Yan, Xiaoqing; Li, Xiaokun; Wang, Guanjun; Li, Wei; Cai, Lu

    2013-01-01

    We studied the protective effect of stromal cell-derived factor-1β (SDF-1β) on cardiac cells from lipotoxicity in vitro and diabetes in vivo. Exposure of cardiac cells to palmitate increased apoptosis by activating NADPH oxidase (NOX)–associated nitrosative stress and endoplasmic reticulum (ER) stress, which was abolished by pretreatment with SDF-1β via upregulation of AMP-activated protein kinase (AMPK)–mediated p38 mitogen-activated protein kinase (MAPK) phosphorylation and interleukin-6 (IL-6) production. The SDF-1β cardiac protection could be abolished by inhibition of AMPK, p38 MAPK, or IL-6. Activation of AMPK or addition of recombinant IL-6 recaptured a similar cardiac protection. SDF-1β receptor C-X-C chemokine receptor type 4 (CXCR4) antagonist AMD3100 or CXCR4 small interfering RNA could not, but CXCR7 small interfering RNA completely abolished SDF-1β’s protection from palmitate-induced apoptosis and activation of AMPK and p38 MAPK. Administration of SDF-1β to diabetic rats, induced by feeding a high-fat diet, followed by a small dose of streptozotocin, could significantly reduce cardiac apoptosis and increase AMPK phosphorylation along with prevention of diabetes-induced cardiac oxidative damage, inflammation, hypertrophy, and remodeling. These results showed that SDF-1β protects against palmitate-induced cardiac apoptosis, which is mediated by NOX-activated nitrosative damage and ER stress, via CXCR7, to activate AMPK/p38 MAPK–mediated IL-6 generation. The cardiac protection by SDF-1β from diabetes-induced oxidative damage, cell death, and remodeling was also associated with AMPK activation. PMID:23423573

  7. Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1{beta}-induced interleukin 6 production and the myeloma proliferative component.

    Science.gov (United States)

    Lust, John A; Lacy, Martha Q; Zeldenrust, Steven R; Dispenzieri, Angela; Gertz, Morie A; Witzig, Thomas E; Kumar, Shaji; Hayman, Suzanne R; Russell, Stephen J; Buadi, Francis K; Geyer, Susan M; Campbell, Megan E; Kyle, Robert A; Rajkumar, S Vincent; Greipp, Philip R; Kline, Michael P; Xiong, Yuning; Moon-Tasson, Laurie L; Donovan, Kathleen A

    2009-02-01

    To conduct in vitro studies as well as a phase 2 clinical trial in patients with smoldering or indolent multiple myeloma to determine if interleukin 1 (IL-1) inhibitors can delay or prevent active myeloma. Stromal cells were cocultured with IL-1beta-expressing myeloma cells in the presence of dexamethasone, IL-1 receptor antagonist (IL-1Ra), or both. Levels of interleukin 6 (IL-6) and of apoptosis were also quantified. Between November 19, 2002, and May 24, 2007, 47 patients were enrolled in the study and subsequently treated with IL-1Ra. In 25 (53%) of the 47 study patients, low-dose dexamethasone (20 mg/wk) was added. The primary end point was progression-free survival (PFS). In vitro, IL-1Ra was superior to dexamethasone at inhibiting IL-6 production; maximal IL-6 inhibition and apoptosis induction were achieved by addition of both IL-1Ra and dexamethasone. In the clinical trial, 3 patients achieved a minor response to IL-1Ra alone; 5 patients achieved a partial response and 4 patients a minor response after addition of dexamethasone. Seven patients showed a decrease in the plasma cell labeling index that paralleled a decrease in high-sensitivity C-reactive protein (hs-CRP) levels. The median overall PFS was 37.5 months. The median PFS for patients without (n=12) or with (n=35) a greater than 15% decrease in 6-month vs baseline hs-CRP levels was 6 months and more than 3 years, respectively (P=.002). Disease stability was maintained in 8 patients who received therapy for more than 4 years. In patients with smoldering or indolent multiple myeloma who were at risk of progression to active myeloma, treatment with IL-1 inhibitors decreased the myeloma proliferative rate and hs-CRP levels in those who responded, leading to a chronic disease state and an improved PFS. clinicaltrials.gov identifier: NCT00635154.

  8. Relationship of serum levels of interleukin 6, interleukin 8, and C-reactive protein with forced expiratory volume in first second in patients with mustard lung and chronic obstructive pulmonary diseases: systematic review and meta-analysis.

    Science.gov (United States)

    Shahriary, Alireza; Panahi, Yunes; Shirali, Saeed; Rahmani, Hossein

    2017-06-01

    The chronic systemic inflammation is a result of releasing inflammatory cytokines from the cells relating to the body immunity system and chronic activation of the innate immunity system. To evaluate the relationship among serum levels of interleukin 6 (IL-6), interleukin 8 (IL-8), C-reactive protein (CRP) with forced expiratory volume in 1 st s (FEV 1 ) in patients with mustard lung (ML) and chronic obstructive pulmonary diseases (COPD). A published literature search was performed through SID, web of science, ISI, Science Direct, Scopus, Medline, and PubMed databases for articles published in English. The correlation coefficient ( r ) and 95% confidence intervals (95% CIs) were calculated using random or fixed effects models. Heterogeneity was assessed using χ 2 and I 2 statistics. In total, 4 published studies were included in the final analysis. Using the random-effect model, meta-analysis showed that the r was -0.052 (95% CI: -0.14-0.049, p = 0.28) at serum level of IL-8, serum levels of CRP and FEV 1 in these results were r = -0.13, p = 0.012, serum levels of tumor necrosis factor (TNF) and FEV 1 levels were r = -0.39, p = 0.03 in the conducted studies on mustard lung patients. The IL-6 serum level was explored in COPD patients. The results of the given studies in these patients are r = -0.006, 95% CI: -0.37-0.15, and p = 0.44. In this meta-analysis, there was evidence that serum levels of CRP and TNF have been significantly increased in chronic obstructive pulmonary diseases compared to the healthy control group, which signifies the presence of systemic inflammation in ML and COPD patients.

  9. A Meta-analysis on the Effect of Ulinastatin on Serum Levels of C-Reactive Protein, Interleukin 6, and Tumor Necrosis Factor Alpha in Asian Patients with Acute Pancreatitis.

    Science.gov (United States)

    Zhang, Chunze; Wang, Yijia; Fu, Wenzheng; Zhang, Weihua; Wang, Tao; Qin, Hai

    2016-03-01

    We aimed to investigate the influence of ulinastatin (UTI) on the serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in Asian patients with acute pancreatitis (AP) by performance of a meta-analysis. Two investigators independently searched 11 databases, including PUBMED, EBSCO, Ovid, SpringerLink, Wiley, Web of Science, Cochrane Library, Wanfang database, China National Knowledge Infrastructure (CNKI), Chinese Journal Full-text Database, and China Biomedicine Database. The full-text articles were screened and the data were extracted using a standardized data extraction form. All statistical analyses were conducted with Stata software, version 12.0 (Stata Corporation, College Station, TX). A total of 94 studies were initially retrieved, and 10 studies containing 424 Asian patients with AP were ultimately enrolled in this meta-analysis. The results revealed that the serum levels of CRP, IL-6, and TNF-α in Asian AP patients significantly decreased after UTI therapy (CRP: standardized mean difference [SMD] = 3.26, 95% confidence interval [CI] = 1.69-4.83, p < 0.001; IL-6: SMD = 5.92, 95% CI = 2.09-9.75, p = 0.002; TNF-α: SMD = 4.07, 95% CI = 0.79-7.35, p = 0.015). The results of this meta-analysis suggest that UTI can effectively depress the serum levels of CRP, IL-6, and TNF-α in Asian patients with AP, and thereby inhibit inflammation.

  10. Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo induces dual effects on the course of acute pancreatitis.

    Science.gov (United States)

    Petrella, C; Agostini, S; Alema', G S; Casolini, P; Carpino, F; Giuli, C; Improta, G; Linari, G; Petrozza, V; Broccardo, M

    2010-11-01

    Cannabinoids (CBs) evoke their effects by activating the cannabinoid receptor subtypes CB1-r and CB2-r and exert anti-inflammatory effects altering chemokine and cytokine expression. Various cytokines and chemokines are produced and released by rodent pancreatic acini in acute pancreatitis. Although CB1-r and CB2-r expressed in rat exocrine pancreatic acinar cells do not modulate digestive enzyme release, whether they modulate inflammatory mediators remains unclear. We investigated the CB-r system role on exocrine pancreas in unstimulated conditions and during acute pancreatitis. We evaluated in vitro and in vivo changes induced by WIN55,212 on the inflammatory variables amylasemia, pancreatic edema and morphology, and on acinar release and content of the cytokine interleukin-6 (IL-6) and chemokine monocyte chemo-attractant protein-1 (MCP-1) in untreated rats and rats with caerulein (CK)-induced pancreatitis. In the in vitro experiments, WIN55,212 (10(-6) mol L(-1)) inhibited IL-6 and MCP-1 release from acinar cells of unstimulated rats and after CK-induced pancreatitis. In vivo, when rats were pretreated with WIN55,212 (2 mg kg(-1), intraperitoneally) before experimentally-induced pancreatitis, serum amylase, pancreatic edema and IL-6 and MCP-1 acinar content diminished and pancreatic morphology improved. Conversely, when rats with experimentally-induced pancreatitis were post-treated with WIN55,212, pancreatitis worsened. These findings provide new evidence showing that the pancreatic CB1-r/CB2-r system modulates pro-inflammatory factor levels in rat exocrine pancreatic acinar cells. The dual, time-dependent WIN55,212-induced changes in the development and course of acute pancreatitis support the idea that the role of the endogenous CB receptor system differs according to the local inflammatory status. © 2010 Blackwell Publishing Ltd.

  11. Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

    Directory of Open Access Journals (Sweden)

    Dexter L. Lee

    2011-01-01

    Full Text Available Peroxisome proliferator-activated receptor-alpha (PPAR-α activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6. Fenofibrate also induces cytochrome P450 4A (CYP4A and increases 20-hydroxyeicosatetraenoic acid (20-HETE production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2, while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically. Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23 and soluble expoxide hydrolase (sEH expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.

  12. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord.

    Science.gov (United States)

    Kawasaki, Yasuhiko; Zhang, Ling; Cheng, Jen-Kun; Ji, Ru-Rong

    2008-05-14

    Central sensitization, increased sensitivity in spinal cord dorsal horn neurons after injuries, plays an essential role in the induction and maintenance of chronic pain. However, synaptic mechanisms underlying central sensitization are incompletely known. Growing evidence suggests that proinflammatory cytokines (PICs), such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha), are induced in the spinal cord under various injury conditions and contribute to pain hypersensitivity. Using patch-clamp recordings in lamina II neurons of isolated spinal cord slices, we compared the effects of IL-1beta, IL-6, and TNFalpha on excitatory and inhibitory synaptic transmission. Whereas TNFalpha enhanced the frequency of spontaneous EPSCs (sEPSCs), IL-6 reduced the frequency of spontaneous IPSCs (sIPSCs). Notably, IL-1beta both enhanced the frequency and amplitude of sEPSCs and reduced the frequency and amplitude of sIPSCs. Consistently, TNFalpha and IL-1beta enhanced AMPA- or NMDA-induced currents, and IL-1beta and IL-6 suppressed GABA- and glycine-induced currents. Furthermore, all the PICs increased cAMP response element-binding protein (CREB) phosphorylation in superficial dorsal horn neurons and produced heat hyperalgesia after spinal injection. Surprisingly, soluble IL-6 receptor (sIL-6R) produced initial decrease of sEPSCs, followed by increase of sEPSCs and CREB phosphorylation. Spinal injection of sIL-6R also induced heat hyperalgesia that was potentiated by coadministration with IL-6. Together, our data have demonstrated that PICs induce central sensitization and hyperalgesia via distinct and overlapping synaptic mechanisms in superficial dorsal horn neurons either by increasing excitatory synaptic transmission or by decreasing inhibitory synaptic transmission. PICs may further induce long-term synaptic plasticity through CREB-mediated gene transcription. Blockade of PIC signaling could be an effective way to suppress

  13. Leukemia inhibitory factor (LIF) enhances MAP2 + and HUC/D + neurons and influences neurite extension during differentiation of neural progenitors derived from human embryonic stem cells.

    Science.gov (United States)

    Leukemia Inhibitory Factor (L1F), a member of the Interleukin 6 cytokine family, has a role in differentiation of Human Neural Progenitor (hNP) cells in vitro. hNP cells, derived from Human Embryonic Stem (hES) cells, have an unlimited capacity for self-renewal in monolayer cultu...

  14. Interleukin 6, lipopolysaccharide-binding protein and interleukin 10 in the prediction of risk and etiologic patterns in patients with community-acquired pneumonia: results from the German competence network CAPNETZ

    Science.gov (United States)

    2012-01-01

    Background The aim of our study was to investigate the predictive value of the biomarkers interleukin 6 (IL-6), interleukin 10 (IL-10) and lipopolysaccharide-binding protein (LBP) compared with clinical CRB and CRB-65 severity scores in patients with community-acquired pneumonia (CAP). Methods Samples and data were obtained from patients enrolled into the German CAPNETZ study group. Samples (blood, sputum and urine) were collected within 24 h of first presentation and inclusion in the CAPNETZ study, and CRB and CRB-65 scores were determined for all patients at the time of enrollment. The combined end point representative of a severe course of CAP was defined as mechanical ventilation, intensive care unit treatment and/or death within 30 days. Overall, a total of 1,000 patients were enrolled in the study. A severe course of CAP was observed in 105 (10.5%) patients. Results The highest IL-6, IL-10 and LBP concentrations were found in patients with CRB-65 scores of 3-4 or CRB scores of 2-3. IL-6 and LBP levels on enrollment in the study were significantly higher for patients with a severe course of CAP than for those who did not have severe CAP. In receiver operating characteristic analyses, the area under the curve values for of IL-6 (0.689), IL-10 (0.665) and LPB (0.624) in a severe course of CAP were lower than that of CRB-65 (0.764) and similar to that of CRB (0.69). The accuracy of both CRB and CRB-65 was increased significantly by including IL-6 measurements. In addition, higher cytokine concentrations were found in patients with typical bacterial infections compared with patients with atypical or viral infections and those with infection of unknown etiology. LBP showed the highest discriminatory power with respect to the etiology of infection. Conclusions IL-6, IL-10 and LBP concentrations were increased in patients with a CRB-65 score of 3-4 and a severe course of CAP. The concentrations of IL-6 and IL-10 reflected the severity of disease in patients with CAP

  15. Hepatitis C Virus-Induced Changes in MicroRNA 107 (miRNA-107) and miRNA-449a Modulate CCL2 by Targeting the Interleukin-6 Receptor Complex in Hepatitis

    Science.gov (United States)

    Sarma, Nayan J.; Tiriveedhi, Venkataswarup; Crippin, Jeffrey S.; Chapman, William C.

    2014-01-01

    ABSTRACT Hepatitis C virus (HCV)-mediated liver diseases are one of the major health issues in the United States and worldwide. HCV infection has been reported to modulate microRNAs (miRNAs) that control various cell surface receptors and gene-regulatory complexes involved in hepatic inflammation and liver diseases. We report here that specific downregulation of miRNA-107 and miRNA-449a following HCV infection in patients with HCV-mediated liver diseases modulates expression of CCL2, an inflammatory chemokine upregulated in patients with chronic liver diseases, by targeting components of the interleukin-6 receptor (IL-6R) complex. Computational analysis for DNA-bound transcription factors in the CCL2 promoter identified adjacent binding sites for CCAAT/CEBPα, spleen focus-forming virus, proviral integration oncogene (SPI1/PU.1), and STAT3. We demonstrate that CEBPα, PU.1, and STAT3 interacted with each other physically to cooperatively bind to the promoter and activate CCL2 expression. Analysis of IL-6R and JAK1 expression in HCV patients by quantitative PCR showed significant upregulation when there was impaired miRNA-107 and miRNA-449a expression, along with upregulation of PU.1 and STAT3, but not CEBPα. miRNA-449a and miRNA-107 target expression of IL-6R and JAK1, respectively, in vitro and also inhibit IL-6 signaling and impair STAT3 activation in human hepatocytes. Taken together, our results demonstrate a novel gene-regulatory mechanism in which HCV-induced changes in miRNAs (miRNA-449a and miRNA-107) regulate CCL2 expression by activation of the IL-6-mediated signaling cascade, which we propose will result in HCV-mediated induction of inflammatory responses and fibrosis. IMPORTANCE Hepatitis C virus (HCV)-induced hepatitis is a major health concern worldwide. HCV infection results in modulation of noncoding microRNAs affecting major cellular pathways, including inflammatory responses. In this study, we have identified a microRNA-regulated pathway for the

  16. СHARACTERISTICS OF THE HEART FATTY ACID-BINDING PROTEIN, INTERLEUKIN-6 AND INTERLEUKIN-8 AS ALTERNATIVE MARKERS OF DIABETIC NEPHROPATHY PROGRESSION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Yu. A. Ryzhikova

    2015-01-01

    Full Text Available The aim of this work was to study the levels of the heart fatty acid-binding protein (h-FABP, interleukin6 (IL-6 and interleukin-8 (IL-8, in diabetic nephropathy (DN in patients with type 1 diabetes mellitus (T1DM. Material and methods. We examined 87 patients aged 18 to 54 with T1DM within the study group. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients – with proteinuria. The control group consisted of 24 healthy donor aged 22 to 29. The comparison group included 22 patients aged 20 to 42 with verified diagnosis of essential arterial hypertension (AH without carbohydrate metabolism disorders. The daily urinary albumin excretion was determined by immunoturbidimetric technique. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients with proteinuria.Calculation of glomerular filtration rate was performed according to the Hoek formula with the use of cystatinС serum concentrations. Contents of h-FABP, IL-6 and cystatin C in serum and h-FABP, IL-8 inurine were determined by enzyme-linked immunosorbent assay. Results. Analysis of the h-FABP content in serum showed that the concentration of this marker in individuals with T1DM was higher than in patients of the control group and the comparison group. Analysis of the h-FABP content in the urine revealed that individuals with essential hypertension showed an increased level of h-FABP while patients with T1DM demonstrated the highest concentration of h-FABP. The concentration of IL-6 inindividuals with T1DM and in individuals with AH significantly exceeded the control values. The contents of h-FABP and IL-6 inserum and h-FABP and IL-8 inurine increased with the progression of DN and reached maximum in individuals of the proteinuria subgroup. At the same time, the levels of h-FABP and IL-8 inthe urine of patients in the microalbuminuria (MAU subgroup were

  17. The influence of short-time period of an adaptation to decreased ambient temperature on interleukin-6 and corticosterone levels in female Wistar strain rats in the proestrous phase of the reproductive cycle.

    Directory of Open Access Journals (Sweden)

    Arkadiusz Baran

    2008-04-01

    Full Text Available To date, there has been little research examining whether short-time changes of external environmental conditions exert any effects on immune responses. The activation of metabolic changes, release of hormones responsive for immunomodulation and the action of interleukins play an important role in interaction with hormones of an anterior pituitary gland in the proestrous phase of the reproductive cycle. The aim of our study was to determine the effects of a short-time change of ambient temperature (30 minutes on interleukin-6 (IL-6 and corticosterone plasma concentration of female rats in the proestrous phase of the reproductive cycle. The climatic chamber with automatically adjustable and monitored internal environmental parameters (temperature, oxygenation, humidity was used during the experiment. The estimation of the vaginal lavage using a microscope was done to determine the estrous cycle. On the day of the experiment, animals were divided into 2 groups: the control group (ambient temperature 21 degrees C +/- 1 degrees C; normoxia 21% O2 and the test group (ambient temperature 10 degrees C +/- 1 degrees C; normoxia 21% O2 stayed in the climatic chamber for 30 minutes. The blood samples were collected before the experiment and after 30, 60, 90, 150 and 210 minutes from the beginning of the experiment. The concentrations of IL-6 and corticosterone were measured in blood plasma samples using ELISA method. There was a significant elevation of IL-6 levels after staying in 10 degrees C during the first 150 minutes from the beginning of the experiment, with the highest value occurring after 60 minutes (426.6 pg/ml; SE - 146.1 with comparison to the value at first sampling (108.5 pg/ml; SE - 29.5; p<0.05 and with comparison to the control group at the same time from the beginning of the experiment (87.6 pg/ml; SE - 2.3; p<0.05. The changed level of corticosterone in the test group in comparison to control group was observed but the differences were

  18. Isorhamnetin inhibits Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages via anti-inflammatory heme oxygenase-1 induction and inhibition of nuclear factor-κB and signal transducer and activator of transcription 1 activation.

    Science.gov (United States)

    Jin, J Y; Choi, E Y; Park, H R; Choi, J I; Choi, I S; Kim, S J

    2013-12-01

    Interleukin-6 (IL-6) is a key proinflammatory cytokine that has been considered to be important in the pathogenesis of periodontal disease. Therefore, host-modulatory agents directed at inhibiting IL-6 appear to be beneficial in terms of attenuating periodontal disease progression and potentially improving disease susceptibility. In the current study, we investigated the effect of the flavonoid isorhamnetin on the production of IL-6 in murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Lipopolysaccharide from P. intermedia ATCC 25611 was isolated using the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time PCR to quantify IL-6 and heme oxygenase-1 (HO-1) mRNA expression. The expression of HO-1 protein and the levels of signaling proteins were monitored using immunoblot analyses. The DNA-binding activity of nuclear factor-κB (NF-κB) was analyzed using ELISA-based assay kits. Isorhamnetin significantly down-regulated P. intermedia LPS-induced production of IL-6 as well as its mRNA expression in RAW264.7 cells. Isorhamnetin up-regulated the expression of HO-1 at both gene transcription and translation levels in cells stimulated with P. intermedia LPS. In addition, inhibition of HO-1 activity by tin protoporphyrin IX blocked the inhibitory effect of isorhamnetin on IL-6 production. Isorhamnetin failed to prevent LPS from activating either c-Jun N-terminal kinase or p38 pathways. Isorhamnetin did not inhibit NF-κB transcriptional activity at the level of inhibitory κB-α degradation. Isorhamnetin suppressed NF-κB signaling through inhibition of nuclear translocation and DNA binding activity of NF-κB p50 subunit and attenuated signal transducer and activator of transcription 1 signaling. Although further research is required to clarify the detailed mechanism of action, we propose

  19. Human herpesvirus 8 interleukin-6 contributes to primary effusion lymphoma cell viability via suppression of proapoptotic cathepsin D, a cointeraction partner of vitamin K epoxide reductase complex subunit 1 variant 2.

    Science.gov (United States)

    Chen, Daming; Gao, Yang; Nicholas, John

    2014-01-01

    Human herpesvirus 8 (HHV-8) interleukin-6 (vIL-6) promotes cell proliferation and survival and is proangiogenic, implicating it as a contributor to virus-associated Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. Although predominantly lytically expressed, vIL-6 is also produced at low, functional levels during latency in PEL cells. Unlike other IL-6 cytokines, vIL-6 is secreted very inefficiently and localizes in the endoplasmic reticulum (ER). ER-localized vIL-6 supports PEL cell proliferation and survival, mediated in part through its interaction with the largely uncharacterized ER-resident protein vitamin K epoxide reductase complex subunit 1 variant 2 (VKORC1v2). Here, we report that the ER-transiting and functionally mitogenic secreted proenzyme (pCatD) form of cathepsin D (mature CatD), a proapoptotic lysosomal aspartate protease, is an interaction partner of VKORC1v2 and that vIL-6 promotes this interaction. Depletion of vIL-6 in PEL cells increased levels of the catalytically active, proteolytically cleaved form of CatD, corresponding with decreased PEL cell viability. Ectopic expression of CatD in PEL cells induced apoptosis, suggesting that CatD suppression by vIL-6 is biologically significant. In the context of high-density culture or reactivation of HHV-8 lytic replication in PEL cells, CatD depletion substantially reduced stress-induced apoptosis and increased virus production. In contrast, CatD overexpression, vIL-6 depletion, and peptide-mediated disruption of vIL-6-VKORC1v2 interaction inhibited replication and cell survival. Combined, our data identify pCatD as an interaction partner of VKORC1v2, demonstrate a role of vIL-6 in CatD suppression via VKORC1v2 in PEL cells, and identify a biologically significant mechanism of vIL-6 prosurvival and proreplication activities via VKORC1v2.

  20. Interleucina 6 e proteína c reativa no diagnóstico de sepse tardia no recém-nascido Interleukins 6 and c - reactive protein for the diagnosis of late onset sepsis in the newborn infant

    Directory of Open Access Journals (Sweden)

    Maria Esther J. R. Ceccon

    2006-04-01

    Full Text Available OBJETIVO: Verificar a acurácia da interleucina 6 (IL-6 e da proteína C reativa (PCR para o diagnóstico de sepse tardia no recém-nascido (RN. MÉTODOS: Trata-se de estudo de coorte prospectivo com 43 RNs internados com suspeita de sepse tardia na UTIN. Foram dosados no dia da suspeita diagnóstica (dia 0 e nos dias 1, 3 e 7 de evolução os níveis séricos da IL-6 e da PCR e calculado o melhor valor de coorte para o diagnóstico de sepse. Também foram calculados os índices de sensibilidade (S, especificidade (E, valor preditivo positivo e negativo (VPP, VPN para cada um dos testes, assim como para a combinação entre eles. RESULTADOS: Os níveis séricos da IL-6 e da PCR estiveram acima do ponto de coorte nos RN com sepse e com sepse presumível com diferenças significantes entre ambos os grupos, nos quais a única diferença foi hemocultura positiva no primeiro. Foi possível afastar esse diagnóstico em seis RNs. Para o diagnóstico de sepse, a IL-6 obteve os melhores índices no dia da suspeita diagnóstica, dia 0 (S: 88,9%, E: 80%, VPP: 76,2%, VPN: 90,9%, seguida da proteína C reativa (S: 94%, E: 78,3%, VPP: 77,3%, VPN: 94,7% 24 horas após. A combinação dos dois (IL 6/PCR mostrou-se mais adequada para o diagnóstico precoce no dia 0 e até 24 horas de evolução com S e VPN de 100%. CONCLUSÃO: A combinação de IL6/PCR apresentou acurácia para o diagnóstico de sepse. A evolução destes testes ao longo dos dias refletiu a evolução clínica dos RN.BACKGROUND: Verify the accuracy of interleukin 6 (IL-6 and C-reactive protein (CRP for diagnosis of late onset sepsis in newborn (NB infants. METHODS: a prospective cohort study with 43 NB infants hospitalized at the NICU with suspicion of late onset sepsis was carried out. Levels of IL-6 and of CRP were dosed with suspicion diagnoses; day (0 and sequentially on day 1, 3, and 7 of the evolution and the best cut-off values were calculated for the diagnoses. Indices of sensibility (S

  1. Asociación entre periodontitis crónica, interleuquina -6 (IL-6 e índice de masa corporal (IMC en embarazadas Association between chronic periodontitis, interleukin-6 (IL-6 and body mass index (BMI in pregnant women

    Directory of Open Access Journals (Sweden)

    S Mella

    2011-12-01

    Full Text Available Objetivo: Determinar si la condición clínica periodontal materna, el índice de masa corporal (IMC y su variación durante el embarazo, se asocian con marcadores de inflamación sistémica: interleuquina-6 (IL-6, factor de necrosis tumoral alfa (TNF- y proteína C reactiva (PCR a nivel plasmático. Material y Método: Estudio clínico que analizó una cohorte de 56 embarazadas entre 18 y 38 años de edad (promedio 27.9 ± 7.04 años, derivadas de la unidad de medicina perinatal en el centro de salud docente asistencial (CESA de la Universidad de los Andes. Todas ellas consintieron voluntariamente su participación en el estudio. En cada trimestre de embarazo, se les realizó un examen periodontal completo, consistente en la determinación de los niveles de inserción clínica, profundidad al sondaje, índice de higiene y sangrado en seis sitios por cada pieza dentaria, excluyendo terceros molares. Adicionalmente, en cada control se obtuvieron muestras de sangre periférica para la determinación de los mediadores proinflamatorios mediante técnica de ELISA. El diagnóstico periodontal y los niveles de mediadores inflamatorios fueron relacionados con la variación del IMC durante el embarazo. Resultados: Las embarazadas con periodontitis crónica presentaron una mayor variación y aumento del índice de masa corporal (p=0.039 y niveles de IL-6 (p=0.026 en comparación con las mujeres embarazadas con gingivitis. Conclusiones: En esta serie de pacientes, se demostró una asociación entre el diagnóstico clínico de periodontitis durante el embarazo con un aumento plasmático de IL-6, así como también una asociación entre un aumento del IMC con los niveles plasmáticos de PCR.Objective: To determine if maternal periodontal clinical status, body mass index (BMI and its variation during pregnancy are associated with increased levels of interleukin-6 (IL-6, tumor necrosis factor alpha (TNF- and C-reactive protein (CRP in plasma. Material and

  2. Interleukin-6 stimulates lipolysis and fat oxidation in humans

    DEFF Research Database (Denmark)

    van Hall, Gerrit; Steensberg, Adam; Sacchetti, Massimo

    2003-01-01

    Although IL-6 is a key modulator of immune function, it also plays a role in regulating substrate metabolism. To determine whether IL-6 affects lipid metabolism, 18 healthy men were infused for 3 h with saline (Con; n = 6) or a high dose (High-rhIL6; n = 6) or a low dose (Low-rhIL6; n = 6) of rec...... in adrenaline, insulin, or glucagon, and no adverse side effects were observed. In conclusion, the data identify IL-6 as a potent modulator of fat metabolism in humans, increasing fat oxidation and FA reesterification without causing hypertriacylglyceridemia....

  3. Significance of Interleukin-6 in Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Toral P. Kobawala

    2016-01-01

    Full Text Available This study sought to reveal the significance of IL-6 in papillary thyroid carcinoma by determining its circulating levels, tumoral protein, and mRNA expressions. As compared to the healthy individuals, serum IL-6 was significantly higher in patients with benign thyroid diseases and PTC. Further, its level was significantly higher in PTC patients as compared to patients with benign thyroid diseases. ROC curves also confirmed a good discriminatory efficacy of serum IL-6 between healthy individuals and patients with benign thyroid diseases and PTC. The circulating IL-6 was significantly associated with poor overall survival in PTC patients. IL-6 immunoreactivity was significantly high in PTC patients as compared to the benign thyroid disease patients. Significantly higher IL-6 mRNA expression was also observed in the primary tumour tissues of PTC patients than the adjacent normal tissues. The protein expression of IL-6 at both the circulating and tissue level correlated with disease aggressiveness in PTC patients. Moreover, a significant positive correlation was observed between the IL-6 protein and mRNA expression in the primary tumours of PTC patients. Finally in conclusion, IL-6 has an important role in thyroid cancer progression. Thus targeting IL-6 signalling can help in clinical management of thyroid carcinoma patients.

  4. Interleukin-6 mediates host defense responses induced by abdominal surgery

    NARCIS (Netherlands)

    Wortel, C. H.; van Deventer, S. J.; Aarden, L. A.; Lygidakis, N. J.; Büller, H. R.; Hoek, F. J.; Horikx, J.; ten Cate, J. W.

    1993-01-01

    Cytokines have been implicated as pivotal mediators of the host defense reaction. In patients undergoing surgery we investigated the relationship between such mediators and postoperative host defense responses. Tumor necrosis factor (TNF) was determined with an immunoradiometric assay, interleukin

  5. Role of Interleukin-6 and Its Receptor in Endometriosis

    OpenAIRE

    Li, Shihui; Fu, Xiaoxia; Wu, Tingting; Yang, Liwei; Hu, Changchang; Wu, RuiJin

    2017-01-01

    Background Studies have shown that the concentration of interleukin (IL)-6 in peritoneal fluid is increased in patients with endometriosis; however, whether the disorders involving IL-6 contribute to the development of endometriosis is still unclear. In the present study, we evaluated the potential role of IL-6 and IL-6 receptor (IL-6R) in the pathogenesis of endometriosis. Material/Methods We examined activated macrophages and the expression of membrane-binding receptor (mIL-6R) in peritonea...

  6. Induction of interleukin-6 by coal containing bioavailable iron is ...

    Indian Academy of Sciences (India)

    Unknown

    occupational analogues, also appear ... ered as one of the human lung pathologies related to oxi- dative stress (Castranova and Vallyathan 2000). ... Human lung epithelial cell line, A549, with characteris- tics of alveolar epithelial type II cells (ATCC ...

  7. Interleukin 6, interleukin 1β, estradiol and testosterone ...

    African Journals Online (AJOL)

    The ovarian physiology is regulated by some complex factors such as hormones and growth factors. The hormones and growth factors are synthesized by follicular and ovarian cells during follicular maturation stage and cytokines are synthesized by the immune system. Interaction between immune and endocrine systems ...

  8. Interleukin 6, interleukin 1β, estradiol and testosterone ...

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... maturation stage and cytokines are synthesized by the immune system. Interaction between immune and endocrine systems modulates ovarian function through the secretion of regulatory soluble factors, especially cytokines. There is a close contact between corona-cumulus-oocyte complex with follicular.

  9. Circulating interleukin-6 and tumor necrosis factor receptor-1 predict ...

    African Journals Online (AJOL)

    Toxic look, constipation, high fever, splenomegaly, increased CRP and ESR were significantly presented in patients who displayed resistance to drug therapy. Both IL-6 and TNF-R1 plasma levels were significantly higher in patients than in control children, and in resistant cases than in responsive cases (before and 5 days ...

  10. Interleukin-6 release from the human brain during prolonged exercise

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Pedersen, Bente Klarlund

    2002-01-01

    be linked with central fatigue, which is enhanced by hyperthermia. Exercise-induced IL-6 may also stimulate hepatic glycogenolysis, which is important during prolonged and repeated exercise. Thus, in a randomised order and separated by 60 min of rest, eight young male subjects completed two 60 min exercise......Interleukin (IL)-6 is a pleiotropic cytokine, which has a variety of physiological roles including functions within the central nervous system. Circulating IL-6 increases markedly during exercise, partly due to the release of IL-6 from the contracting skeletal muscles, and exercise-induced IL-6 may...... in the brain at rest or after 15 min of exercise, but a small release of IL-6 was observed after 60 min of exercise in the first bout (0.06 +/- 0.03 ng min(-1)). This release of IL-6 from the brain was five-fold greater at the end of the second bout (0.30 +/- 0.08 ng min(-1); P

  11. Interleukin-6 release from the human brain during prolonged exercise

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Pedersen, Bente Klarlund

    2002-01-01

    bouts: one bout with a normal (38 degrees C) and the other with an elevated (39.5 degrees C) core temperature. The cerebral IL-6 response was determined on the basis of internal jugular venous to arterial IL-6 differences and global cerebral blood flow. There was no net release or uptake of IL-6...... influence of hyperthermia. In conclusion, IL-6 is released from the brain during prolonged exercise in humans and it appears that the duration of the exercise rather than the increase in body temperature dictates the cerebral IL-6 response....

  12. Induction of interleukin-6 by coal containing bioavailable iron is ...

    Indian Academy of Sciences (India)

    We found that levels of IL-6 protein as well as its mRNA were significantly increased in the cells treated for 24 h with 20 g/cm2 of the BAI-containing Pennsylvania (PA) coal; for example we observed 6.7–fold increase in IL-6 protein. Levels of IL-6 protein in cells treated with the Utah (UT) coal containing low-BAI were only ...

  13. The relationship between serum bilirubin level with interleukin.6 ...

    African Journals Online (AJOL)

    Context: Bilirubin has been shown to influence the mechanisms of both apoptosis and inflammation. Aims: The aim of the following study is to investigate the relationship between the serum bilirubin level with sepsis progression. Settings and Design: A total of 20 patients from intensive care unit were included for this study.

  14. Induction of interleukin-6 by coal containing bioavailable iron is ...

    Indian Academy of Sciences (India)

    Coal mining causes health problems, such as pneumoconiosis. We have previously shown that prevalence of pneumoconiosis in workers from various coalmine regions positively correlates with levels of bioavailable iron (BAI) in the coals from that region. In the present study, the nature of reactive oxygen species formed ...

  15. Circulating interleukin-6 and tumor necrosis factor receptor-1 predict ...

    African Journals Online (AJOL)

    EL-HAKIM

    INTRODUCTION. Typhoid fever, encountered in all parts of the world, is nowadays primarily found in countries where sanitary conditions are poor. It is considered to be one of the most important and under-reported diseases in the developing world. In some areas, it has been estimated that typhoid fever is responsible.

  16. Effect of interleukin-6 polymorphisms on human longevity

    DEFF Research Database (Denmark)

    Di Bona, Danilo; Vasto, Sonya; Capurso, Cristiano

    2009-01-01

    -6 levels. However, discordant results have been obtained. To explore the relationship between this polymorphism and longevity, we analyzed individual data on long-living subjects and controls from eight case-control studies conducted in Europeans, using meta-analysis. There was no significant...

  17. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Science.gov (United States)

    Vázquez-Del Mercado, Mónica; Nuñez-Atahualpa, Lourdes; Figueroa-Sánchez, Mauricio; Gómez-Bañuelos, Eduardo; Rocha-Muñoz, Alberto Daniel; Martín-Márquez, Beatriz Teresita; Martínez-García, Erika Aurora; Macias-Reyes, Héctor; Gamez-Nava, Jorge Ivan; Navarro-Hernandez, Rosa Elena; Nuñez-Atahualpa, María Alejandra; Andrade-Garduño, Javier

    2015-01-01

    The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P < 0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P < 0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P = 0.02). The cIMT correlated with levels of anti-CCP (r = 0.513, P = 0.001), CRP (r = 0.799, P < 0.001), TNFα (r = 0.642, P = 0.001), and IL-6 (r = 0.751, P < 0.001). In multiple regression analysis, cIMT was associated with CRP (P < 0.001) and anti-CCP levels (P = 0.03). Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events. PMID:25821796

  18. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Mónica Vázquez-Del Mercado

    2015-01-01

    Full Text Available The main cause of death in rheumatoid arthritis (RA is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP antibody levels with increased carotid intima-media thickness (cIMT in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC were studied. All groups were assessed for atherogenic index of plasma (AIP and cIMT. Anti-CCP, C-reactive protein (CRP, and levels of tumor necrosis factor alpha (TNFα and interleukin-6 (IL-6 were measured by enzyme-linked immunosorbent assay (ELISA. Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P<0.001. Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P<0.01, and lower levels of high density lipoprotein cholesterol (HDL-c (P=0.02. The cIMT correlated with levels of anti-CCP (r=0.513, P=0.001, CRP (r=0.799, P<0.001, TNFα (r=0.642, P=0.001, and IL-6 (r=0.751, P<0.001. In multiple regression analysis, cIMT was associated with CRP (P<0.001 and anti-CCP levels (P=0.03. Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events.

  19. Polymorphisms cyclooxygenase-2 -765G>C and interleukin-6 -174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts.

    Science.gov (United States)

    Corella, Dolores; González, José Ignacio; Bulló, Mònica; Carrasco, Paula; Portolés, Olga; Díez-Espino, Javier; Covas, María Isabel; Ruíz-Gutierrez, Valentina; Gómez-Gracia, Enrique; Arós, Fernando; Fiol, Miquel; Herrera, Manuel Conde; Santos, José Manuel; Sáez, Guillermo; Lamuela, Rosa; Lahoz, Carlos; Vinyoles, Ernest; Ros, Emilio; Estruch, Ramón

    2009-01-01

    Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G>C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G>C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response to a nutritional intervention with MD. An intervention study in a high cardiovascular risk Mediterranean population (314 men and 407 women) was undertaken. Participants were randomly assigned to consume a low-fat control diet or a MD supplemented with virgin olive oil or nuts. Measures were obtained at baseline and after a 3-mo intervention period. At baseline, the COX-2 -765G>C polymorphism was associated with lower serum IL-6 (5.85 +/- 4.82 in GG vs. 4.74 +/- 4.14 ng/L in C-allele carriers; P = 0.002) and ICAM-1 (265.8 +/- 114.8 in GG vs. 243.0 +/- 107.1 microg/L in C-carriers; P = 0.018) concentrations. These differences remained significant after multivariate adjustment. The IL-6 -174G>C polymorphism was associated with higher (CC vs. G-carriers) serum ICAM-1 concentrations in both men and women and with higher serum IL-6 concentrations in men. Following the dietary intervention, no significant gene x diet interactions were found. In conclusion, although COX-2 -765G>C and IL-6 -174G>C polymorphisms were associated with inflammation, consuming a MD (either supplemented with virgin olive oil or nuts) reduced the concentration of inflammation markers regardless of these polymorphisms.

  20. The intestinal tract as the major source of interleukin 6 production during abdominal aortic clamping and hind limb ischaemia-reperfusion injury O trato intestinal como a principal fonte na producao de interleucina 6 durante clampeamento da aorta abdominal e lesão de isquemia/rererfusão de membros inferiores

    Directory of Open Access Journals (Sweden)

    Márcio Benedito Palma Pimenta

    2007-01-01

    Full Text Available PURPOSE: The aim of this study was to investigate whether the hind limbs or intestinal tract is the most important initiator of the inflammatory response secondary aortic clamping and hind limb ischemia/reperfusion injury. METHODS: Blood samples of Wistar rats obtained from posterior cava vein, portal vein, and heart cavity during either laparotomy (control group, n=8 or laparotomy + 2 h of aortic clamping and bilateral hind limb ischemia (ischemia group, n=8, or 2 h after ischemia and 2 h of reperfusion (ischemia-reperfusion group, n=8 were assayed for interleukin 6 (IL-6 and C-reactive protein (CRP. RESULTS: Serum IL-6 at the heart (223.6±197.9 [10-832] pg/mL was higher (pOBJETIVO: Investigar qual o principal mediador da resposta inflamatória na lesao de isquemia/reperfusão após clampeamento da aorta abdominal e isquemia dos membros inferiores: o intestine ou as extremidades inferiores. MÉTODOS: amostra de sangue de ratos Wistar coletados da cava posterior, porta e cavidade cardíaca during tanto laparotomia (grupo controle n=8 ou laparotomia + 2 horas de clampeamento aórtico e isquemia bilateral de membros posteriores (grupo isquemia n=8, ou 2 h de isquemia seguido por 2 horas de reperfusão (grupo isquemia/reperfusão n=8, onde foram dosados interleucina 6 e proteína C-reativa. RESULTADOS: Il-6 no coração (223.6±197.9 [10-832] pg/mL foi maior (p<0.001 tanto na veia porta (133.08±108.52 [4-372] pg/mL quanto na veia cava posterior (127.58±109.15 [8-388] pg/mL. PCR não foi significativamente diferente entre os grupos. CONCLUSÃO: o trato intestinal foi responsável pela resposta inflamatória secundária a lesão de isquemia/reperfusão.

  1. Fator de inibição da migração de macrófagos e interleucina-6 na síndrome de esmagamento: analogia com gravidade? Relato de casos Macrophage migration inhibitory factor and interleukin-6 in crush syndrome: analogy with severity? Case reports

    Directory of Open Access Journals (Sweden)

    Rita C. Vianna de Azevedo

    2007-12-01

    . Interleukin-6 (IL-6 is a proinflammatory cytokine that plays an important role in the initial inflammatory response to trauma and the development of early and late multiple organ dysfunction syndrome (MODS. Crush syndrome has been described as the systemic manifestation of muscle cell damage resulting from pressing or crushing. There are few data about MIF and IL-6 in crush syndrome. The aim of this study was to report four cases of crush syndrome, measuring seric levels of MIF and IL-6 and its correlation with severity. CASES REPORTS: Four patients suffering from crush syndrome after an accident with an explosive artifact were enrolled in the study. APACHE II score was checked at admission. It was collected serum sample of these patients during six consecutive days. Serum MIF, IL-6 and creatine kinase (CK were measured. Sepsis-related organ failure assessment (SOFA score was evaluated concomitantly. Data were analyzed. CONCLUSIONS: The variations observed in the CK measures were followed by alterations in the cytokines' level and at the SOFA score, suggesting interdependence between those factors. Other articles have already demonstrated similar results. Although the use of cytokines as biomarkers of severity in trauma is matter of interest, we need large studies with a higher number of patients to validate this observation.

  2. Constraint Differentiation

    DEFF Research Database (Denmark)

    Mödersheim, Sebastian Alexander; Basin, David; Viganò, Luca

    2010-01-01

    We introduce constraint differentiation, a powerful technique for reducing search when model-checking security protocols using constraint-based methods. Constraint differentiation works by eliminating certain kinds of redundancies that arise in the search space when using constraints to represent...... results show that constraint differentiation substantially reduces search and considerably improves the performance of OFMC, enabling its application to a wider class of problems....

  3. Differential manifolds

    CERN Document Server

    Kosinski, Antoni A

    2007-01-01

    The concepts of differential topology form the center of many mathematical disciplines such as differential geometry and Lie group theory. Differential Manifolds presents to advanced undergraduates and graduate students the systematic study of the topological structure of smooth manifolds. Author Antoni A. Kosinski, Professor Emeritus of Mathematics at Rutgers University, offers an accessible approach to both the h-cobordism theorem and the classification of differential structures on spheres.""How useful it is,"" noted the Bulletin of the American Mathematical Society, ""to have a single, sho

  4. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma.

    Science.gov (United States)

    Yang, Xuexian O; Pappu, Bhanu P; Nurieva, Roza; Akimzhanov, Askar; Kang, Hong Soon; Chung, Yeonseok; Ma, Li; Shah, Bhavin; Panopoulos, Athanasia D; Schluns, Kimberly S; Watowich, Stephanie S; Tian, Qiang; Jetten, Anton M; Dong, Chen

    2008-01-01

    T cell functional differentiation is mediated by lineage-specific transcription factors. T helper 17 (Th17) has been recently identified as a distinct Th lineage mediating tissue inflammation. Retinoic acid receptor-related orphan receptor gamma (ROR gamma) was shown to regulate Th17 differentiation; ROR gamma deficiency, however, did not completely abolish Th17 cytokine expression. Here, we report Th17 cells highly expressed another related nuclear receptor, ROR alpha, induced by transforming growth factor-beta and interleukin-6 (IL-6), which is dependent on signal transducer and activator of transcription 3. Overexpression of ROR alpha promoted Th17 differentiation, possibly through the conserved noncoding sequence 2 in Il17-Il17f locus. ROR alpha deficiency resulted in reduced IL-17 expression in vitro and in vivo. Furthermore, ROR alpha and ROR gamma coexpression synergistically led to greater Th17 differentiation. Double deficiencies in ROR alpha and ROR gamma globally impaired Th17 generation and completely protected mice against experimental autoimmune encephalomyelitis. Therefore, Th17 differentiation is directed by two lineage-specific nuclear receptors, ROR alpha and ROR gamma.

  5. Differential games.

    Science.gov (United States)

    Varaiya, P. P.

    1972-01-01

    General discussion of the theory of differential games with two players and zero sum. Games starting at a fixed initial state and ending at a fixed final time are analyzed. Strategies for the games are defined. The existence of saddle values and saddle points is considered. A stochastic version of a differential game is used to examine the synthesis problem.

  6. Differential games

    CERN Document Server

    Friedman, Avner

    2006-01-01

    This volume lays the mathematical foundations for the theory of differential games, developing a rigorous mathematical framework with existence theorems. It begins with a precise definition of a differential game and advances to considerations of games of fixed duration, games of pursuit and evasion, the computation of saddle points, games of survival, and games with restricted phase coordinates. Final chapters cover selected topics (including capturability and games with delayed information) and N-person games.Geared toward graduate students, Differential Games will be of particular interest

  7. Differential Geometry

    CERN Document Server

    Stoker, J J

    2011-01-01

    This classic work is now available in an unabridged paperback edition. Stoker makes this fertile branch of mathematics accessible to the nonspecialist by the use of three different notations: vector algebra and calculus, tensor calculus, and the notation devised by Cartan, which employs invariant differential forms as elements in an algebra due to Grassman, combined with an operation called exterior differentiation. Assumed are a passing acquaintance with linear algebra and the basic elements of analysis.

  8. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6

    DEFF Research Database (Denmark)

    Steensberg, A; Van Hall, Gerrit; Osada, T

    2000-01-01

    1. Plasma interleukin (IL)-6 concentration is increased with exercise and it has been demonstrated that contracting muscles can produce IL-The question addressed in the present study was whether the IL-6 production by contracting skeletal muscle is of such a magnitude that it can account for the IL...... followed the same pattern as did the net IL-6 release. Over the resting leg, there was no significant a-fv difference or net IL-6 release. The work was produced by 2.5 kg of active muscle, which means that during the last 2 h of exercise, the median IL-6 production was 6.8 ng min-1 (kg active muscle)-1...... of IL-6 during muscular exercise. We suggest that IL-6 produced by skeletal contracting muscle contributes to the maintenance of glucose homeostasis during prolonged exercise....

  9. Presence of interleukin 6 at the cutaneous level after in vivo neutron irradiation; Presence d`interleukine 6 au niveau cutane apres irradiation neutronique in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Agay, D.; Pradeau, P.; Edgard, L.; Van Uye, A.; Mestries, J.C.

    1994-12-31

    In this study we investigated the in situ localization of IL-6 in mixed neutron-gamma irradiated baboons belly skin. Using immunohistochemical methods, we demonstrated the presence of IL-6 as early as the first day after the irradiation day. However experimental conditions did not allow us to conclude to a causality relation between irradiation and IL-6 cutaneous presence. (author). 4 refs.

  10. Reversing SKI-SMAD4-mediated suppression is essential for TH17 cell differentiation.

    Science.gov (United States)

    Zhang, Song; Takaku, Motoki; Zou, Liyun; Gu, Ai-di; Chou, Wei-Chun; Zhang, Ge; Wu, Bing; Kong, Qing; Thomas, Seddon Y; Serody, Jonathan S; Chen, Xian; Xu, Xiaojiang; Wade, Paul A; Cook, Donald N; Ting, Jenny P Y; Wan, Yisong Y

    2017-11-02

    T helper 17 (T H 17) cells are critically involved in host defence, inflammation, and autoimmunity. Transforming growth factor β (TGFβ) is instrumental in T H 17 cell differentiation by cooperating with interleukin-6 (refs 6, 7). Yet, the mechanism by which TGFβ enables T H 17 cell differentiation remains elusive. Here we reveal that TGFβ enables T H 17 cell differentiation by reversing SKI-SMAD4-mediated suppression of the expression of the retinoic acid receptor (RAR)-related orphan receptor γt (RORγt). We found that, unlike wild-type T cells, SMAD4-deficient T cells differentiate into T H 17 cells in the absence of TGFβ signalling in a RORγt-dependent manner. Ectopic SMAD4 expression suppresses RORγt expression and T H 17 cell differentiation of SMAD4-deficient T cells. However, TGFβ neutralizes SMAD4-mediated suppression without affecting SMAD4 binding to the Rorc locus. Proteomic analysis revealed that SMAD4 interacts with SKI, a transcriptional repressor that is degraded upon TGFβ stimulation. SKI controls histone acetylation and deacetylation of the Rorc locus and T H 17 cell differentiation via SMAD4: ectopic SKI expression inhibits H3K9 acetylation of the Rorc locus, Rorc expression, and T H 17 cell differentiation in a SMAD4-dependent manner. Therefore, TGFβ-induced disruption of SKI reverses SKI-SMAD4-mediated suppression of RORγt to enable T H 17 cell differentiation. This study reveals a critical mechanism by which TGFβ controls T H 17 cell differentiation and uncovers the SKI-SMAD4 axis as a potential therapeutic target for treating T H 17-related diseases.

  11. Differential Effects of Planktonic and Biofilm MRSA on Human Fibroblasts

    Science.gov (United States)

    Kirker, Kelly R.; James, Garth A.; Fleckman, Philip; Olerud, John E.; Stewart, Philip S.

    2012-01-01

    Bacteria colonizing chronic wounds often exist as biofilms, yet their role in chronic wound pathogenesis remains unclear. Staphylococcus aureus biofilms induce apoptosis in dermal keratinocytes, and given that chronic wound biofilms also colonize dermal tissue, it is important to investigate the effects of bacterial biofilms on dermal fibroblasts. The effects of a predominant wound pathogen, methicillin-resistant S. aureus, on normal, human, dermal fibroblasts were examined in vitro. Cell culture medium was conditioned with equivalent numbers of either planktonic or biofilm methicillin-resistant S. aureus, and then fed to fibroblast cultures. Fibroblast response was evaluated using scratch, viability, and apoptosis assays. The results suggested that fibroblasts experience the same fate when exposed to the soluble products of either planktonic or biofilm methicillin-resistant S. aureus, namely limited migration followed by death. Enzyme-linked immunosorbent assays demonstrated that fibroblast production of cytokines, growth factors, and proteases were differentially affected by planktonic and biofilm-conditioned medium. Planktonic-conditioned medium induced more interleukin-6, interleukin-8, vascular endothelial growth factor, transforming growth factor-β1, heparin-bound epidermal growth factor, matrix metalloproteinase-1, and metalloproteinase-3 production in fibroblasts than the biofilm-conditioned medium. Biofilm-conditioned medium induced more tumor-necrosis factor-α production in fibroblasts compared to planktonic-conditioned medium, and suppressed metalloproteinase-3 production compared to controls. PMID:22332802

  12. Differential belongings

    DEFF Research Database (Denmark)

    Oldrup, Helene

    2014-01-01

    This paper explores suburban middle-class residents’ narratives about housing choice, everyday life and belonging in residential areas of Greater Copenhagen, Denmark, to understand how residential processes of social differentiation are constituted. Using Savage et al.’s concepts of discursive...

  13. Serum inflammatory markers in the elderly: are they useful in differentiating sepsis from SIRS?

    Directory of Open Access Journals (Sweden)

    Mahshid Talebi-Taher

    2014-06-01

    Full Text Available Differentiating sepsis from other noninfectious causes of systemic inflammation is often difficult in the elderly. The aim of this study was to evaluate the ability of C-reactive protein (CRP, Erythrocyte Sedimentation Rate (ESR, procalcitonin (PCT, and Interleukin-6 (IL-6 to identify elderly patients with sepsis. In this single center prospective observational study, we included all consecutive elderly patients admitted with suspected sepsis and systemic inflammatory response syndrome (SIRS in an emergency department. Blood samples for measuring CRP, PCT, IL-6, ESR and white blood cells (WBC count were taken at first day of admission. Sensitivity, specificity, positive and negative predictive values were calculated for each inflammatory markers being studied. A total of 150 elderly patients aged 65 and older, 50 with sepsis and 50 with SIRS, and fifty individuals in a normal health status were included. CRP exhibited the greatest sensitivity (98% and negative predictive value (98.6% and performed best in differentiating patients with sepsis from those with SIRS. In a receiver operating characteristic curve analysis, IL-6 performed best in distinguishing between SIRS and the control group (AUC 0.75, 95% CI. On the other hand, both CRP and ESR appeared to be a more accurate diagnostic parameter for differentiating sepsis from SIRS among elderly patients.

  14. Serum inflammatory markers in the elderly: are they useful in differentiating sepsis from SIRS?

    Science.gov (United States)

    Talebi-Taher, Mahshid; Babazadeh, Shahin; Barati, Mitra; Latifnia, Maryam

    2014-01-01

    Differentiating sepsis from other noninfectious causes of systemic inflammation is often difficult in the elderly. The aim of this study was to evaluate the ability of C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), procalcitonin (PCT), and Interleukin-6 (IL-6) to identify elderly patients with sepsis. In this single center prospective observational study, we included all consecutive elderly patients admitted with suspected sepsis and systemic inflammatory response syndrome (SIRS) in an emergency department. Blood samples for measuring CRP, PCT, IL-6, ESR and white blood cells (WBC) count were taken at first day of admission. Sensitivity, specificity, positive and negative predictive values were calculated for each inflammatory markers being studied. A total of 150 elderly patients aged 65 and older, 50 with sepsis and 50 with SIRS, and fifty individuals in a normal health status were included. CRP exhibited the greatest sensitivity (98%) and negative predictive value (98.6%) and performed best in differentiating patients with sepsis from those with SIRS. In a receiver operating characteristic curve analysis, IL-6 performed best in distinguishing between SIRS and the control group (AUC 0.75, 95% CI). On the other hand, both CRP and ESR appeared to be a more accurate diagnostic parameter for differentiating sepsis from SIRS among elderly patients.

  15. Níveis séricos de interleucina-6 (IL-6, interleucina-18 (IL-18 e proteína C reativa (PCR na síndrome coronariana aguda sem supradesnivelamento do ST em pacientes com diabete tipo 2 Serum levels of interleukin-6 (Il-6, interleukin-18 (Il-18 and C-reactive protein (CRP in patients with type-2 diabetes and acute coronary syndrome without ST-segment elevation

    Directory of Open Access Journals (Sweden)

    José Roberto Matos Souza

    2008-02-01

    Full Text Available FUNDAMENTO: A aterosclerose é uma doença inflamatória e níveis séricos de marcadores inflamatórios, como a interleucina 6 (IL-6, interleucina-18 (IL-18 e proteína C reativa (PCR, são utilizados para avaliação de pacientes em quadros de coronariopatia. No paciente com diabete do tipo 2, a aterosclerose está relacionada a um maior número de eventos como infarto e morte, quando comparado aos pacientes sem diabete. OBJETIVO: Avaliar a resposta inflamatória nos pacientes com diabete e eventos agudos de instabilidade coronariana. MÉTODOS: Selecionamos primariamente dois grupos de pacientes. O primeiro grupo foi composto por pacientes ambulatoriais diabéticos com angina estável (D-SCC e presença de coronariopatia ao estudo coronariográfico (n = 36. O segundo grupo foi composto por pacientes diabéticos atendidos no pronto-socorro com quadro de síndrome coronariana aguda (D-SCA sem supradesnivelamento do ST (n = 38. Como controle, foram utilizados pacientes sem diabete com SCA (n = 22 e SCC (n = 16. As concentrações séricas de PCR, IL-6 e IL-18 foram determinadas pelas técnicas de nefelometria (PCR e ELISA (IL-6 e IL-18. RESULTADOS: Níveis mais elevados de IL-6 foram observados em pacientes com ou sem diabete e SCA em relação ao grupo com SCC. Por sua vez, pacientes com diabete e SCA apresentaram concentrações maiores de PCR em comparação aos outros grupos. Os níveis séricos de IL-18 não diferiram significativamente entre os pacientes estudados. CONCLUSÃO: Os resultados obtidos sugerem uma maior atividade inflamatória no paciente com quadro de instabilidade coronariana. Essa atividade inflamatória, medida pela PCR, parece ser ainda mais intensa no paciente com diabete.BACKGROUND: Atherosclerosis is an inflammatory disease, and serum levels of inflammatory markers such as interleukin 6 (IL-6, interleukin 18 (IL-18 and C-reactive protein (CRP are used to evaluate patients with coronary artery disease. In patients with

  16. Differential discriminator

    International Nuclear Information System (INIS)

    Dukhanov, V.I.; Mazurov, I.B.

    1981-01-01

    A principal flowsheet of a differential discriminator intended for operation in a spectrometric circuit with statistical time distribution of pulses is described. The differential discriminator includes four integrated discriminators and a channel of piled-up signal rejection. The presence of the rejection channel enables the discriminator to operate effectively at loads of 14x10 3 pulse/s. The temperature instability of the discrimination thresholds equals 250 μV/ 0 C. The discrimination level changes within 0.1-5 V, the level shift constitutes 0.5% for the filling ratio of 1:10. The rejection coefficient is not less than 90%. Alpha spectrum of the 228 Th source is presented to evaluate the discriminator operation with the rejector. The rejector provides 50 ns time resolution

  17. Differential topology

    CERN Document Server

    Margalef-Roig, J

    1992-01-01

    ...there are reasons enough to warrant a coherent treatment of the main body of differential topology in the realm of Banach manifolds, which is at the same time correct and complete. This book fills the gap: whenever possible the manifolds treated are Banach manifolds with corners. Corners add to the complications and the authors have carefully fathomed the validity of all main results at corners. Even in finite dimensions some results at corners are more complete and better thought out here than elsewhere in the literature. The proofs are correct and with all details. I see this book as a reliable monograph of a well-defined subject; the possibility to fall back to it adds to the feeling of security when climbing in the more dangerous realms of infinite dimensional differential geometry. Peter W. Michor

  18. Hepatocyte differentiation.

    Science.gov (United States)

    Olsavsky Goyak, Katy M; Laurenzana, Elizabeth M; Omiecinski, Curtis J

    2010-01-01

    Increasingly, research suggests that for certain systems, animal models are insufficient for human toxicology testing. The development of robust, in vitro models of human toxicity is required to decrease our dependence on potentially misleading in vivo animal studies. A critical development in human toxicology testing is the use of human primary hepatocytes to model processes that occur in the intact liver. However, in order to serve as an appropriate model, primary hepatocytes must be maintained in such a way that they persist in their differentiated state. While many hepatocyte culture methods exist, the two-dimensional collagen "sandwich" system combined with a serum-free medium, supplemented with physiological glucocorticoid concentrations, appears to robustly maintain hepatocyte character. Studies in rat and human hepatocytes have shown that when cultured under these conditions, hepatocytes maintain many markers of differentiation including morphology, expression of plasma proteins, hepatic nuclear factors, phase I and II metabolic enzymes. Functionally, these culture conditions also preserve hepatic stress response pathways, such as the SAPK and MAPK pathways, as well as prototypical xenobiotic induction responses. This chapter will briefly review culture methodologies but will primarily focus on hallmark hepatocyte structural, expression and functional markers that characterize the differentiation status of the hepatocyte.

  19. What differentiates a differential psychopharmacology?

    OpenAIRE

    Krüger, Hans-Peter

    2010-01-01

    The methodological implications of a differential psychopharmacology are discussed. It is shown that the technique of stratifying subjects with personality scores depends on one basic assumption: the personality score is not affected by the other experimental factors. Two experiments are reported in which pre- and posttest (after the experiment) scores were measured. The pre-post-differences showed themselves to be affected by the medication. It is argued that in psychopharmacological experim...

  20. Differential geometry

    CERN Document Server

    Ciarlet, Philippe G

    2007-01-01

    This book gives the basic notions of differential geometry, such as the metric tensor, the Riemann curvature tensor, the fundamental forms of a surface, covariant derivatives, and the fundamental theorem of surface theory in a selfcontained and accessible manner. Although the field is often considered a classical one, it has recently been rejuvenated, thanks to the manifold applications where it plays an essential role. The book presents some important applications to shells, such as the theory of linearly and nonlinearly elastic shells, the implementation of numerical methods for shells, and

  1. Differential equations

    CERN Document Server

    Tricomi, FG

    2013-01-01

    Based on his extensive experience as an educator, F. G. Tricomi wrote this practical and concise teaching text to offer a clear idea of the problems and methods of the theory of differential equations. The treatment is geared toward advanced undergraduates and graduate students and addresses only questions that can be resolved with rigor and simplicity.Starting with a consideration of the existence and uniqueness theorem, the text advances to the behavior of the characteristics of a first-order equation, boundary problems for second-order linear equations, asymptotic methods, and diff

  2. Differential topology

    CERN Document Server

    Guillemin, Victor

    2010-01-01

    Differential Topology provides an elementary and intuitive introduction to the study of smooth manifolds. In the years since its first publication, Guillemin and Pollack's book has become a standard text on the subject. It is a jewel of mathematical exposition, judiciously picking exactly the right mixture of detail and generality to display the richness within. The text is mostly self-contained, requiring only undergraduate analysis and linear algebra. By relying on a unifying idea-transversality-the authors are able to avoid the use of big machinery or ad hoc techniques to establish the main

  3. The effects of 6-gingerol on proliferation, differentiation, and maturation of osteoblast-like MG-63 cells

    Energy Technology Data Exchange (ETDEWEB)

    Fan, J.Z.; Yang, X.; Bi, Z.G. [Department of Orthopedic Surgery, First Affiliated Hospital, Harbin Medicine University, Harbin (China)

    2015-04-28

    We investigated whether 6-gingerol affects the maturation and proliferation of osteoblast-like MG63 cells in vitro. Osteoblast-like MG63 cells were treated with 6-gingerol under control conditions, and experimental inflammation was induced by tumor necrosis factor-α (TNF-α). Expression of different osteogenic markers and cytokines was analyzed by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay. In addition, alkaline phosphatase (ALP) enzyme activity and biomineralization as markers for differentiation were measured. Treatment with 6-gingerol resulted in insignificant effects on the proliferation rate. 6-Gingerol induced the differentiation of osteoblast-like cells with increased transcription levels of osteogenic markers, upregulated ALP enzyme activity, and enhanced mineralized nodule formation. Stimulation with TNF-α led to enhanced interleukin-6 and nuclear factor-κB expression and downregulated markers of osteoblastic differentiation. 6-Gingerol reduced the degree of inflammation in TNF-α-treated MG-63 cells. In conclusion, 6-gingerol stimulated osteoblast differentiation in normal physiological and inflammatory settings, and therefore, 6-gingerol represents a promising agent for treating osteoporosis or bone inflammation.

  4. Differences of serum interleukin-6 levels in normotensive and preeclampsia women

    Science.gov (United States)

    Lumbanraja, S. N.; Junitasari, R.; Pasaribu, H. P.

    2018-03-01

    Red cell distribution width (RDW) has been shown higher with the increase of inflammatory activity. As CD4 count is not available in all cities in Indonesia, RDW was hoped to be the next promising marker to predict the progression of HIV infection. This study aims to find the association of RDW with aCD4 count in HIV-positive reproductive women in Indonesia. It was a prospective cross sectional study enrolled 37 consented outpatients HIV-positive reproductive women in Haji Adam Malik General Hospital, Medan, Indonesia. A 10 mL blood was taken, separated into two tubes for complete blood count and CD4 count. Data were collected and analyzed with SPSS 19.Mean CD4 absolute was lowest in >14.5% RDW group but without statistical significance. By classify CD4 absolute count, CD4 absolute ≤350/mm3 showed significantly higher RDW than CD4 absolute >350/mm3 (13.98±2.10% vs 12.79±0.88% p=0.02). No correlation was between RDW and CD4 absolute, as well as, with CD4%.In conclusion, high RDW can be a promising marker to predict the low CD4 count in HIV-positive reproductive women within antiretroviral therapy.

  5. Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells

    OpenAIRE

    Ogawa, Hiroyuki; Koyanagi-Aoi, Michiyo; Otani, Kyoko; Zen, Yoh; Maniwa, Yoshimasa; Aoi, Takashi

    2017-01-01

    In the present study, we successfully generated lung cancer stem cell (CSC)-like cells by introducing a small set of transcription factors into a lung cancer cell line. In addition to properties that are conventionally referred to as CSC properties, the lung induced CSCs exhibited the ability to form lung cancer-like tissues in vitro with vascular cells and mesenchymal stem cells, which showed structures and immunohistological patterns that were similar to human lung cancer tissues. We named ...

  6. Serum interleukin-6 is related to lower cognitive functioning in elderly patients with major depression.

    Science.gov (United States)

    Ali, Nehad Samir; Hashem, Abdel Hamid Hashem; Hassan, Akmal Mostafa; Saleh, Alia Adel; El-Baz, Heba Nabil

    2017-03-24

    There is an increased evidence of an association between inflammatory mediators, particularly serum IL-6, depression and cognitive impairment in the elderly. This study aims at exploring the relation of peripheral IL-6 to cognitive functions in elderly patients with major depressive disorder (MDD). (1) Assessment of serum IL-6 levels and cognitive functions in elderly patients suffering from major depression and comparing them to healthy age-matched control subjects; (2) correlation between serum IL-6 levels and clinical characteristics of depression and cognitive functions in these patients. The study is an observational, case-control study. It consisted of 80 subjects, 40 with the diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR) with early onset (first episode before the age of 60) and 40 community-dwelling subjects. They were subjected to the Structured Clinical Interview according to DSM-IV, Montreal Cognitive Assessment, Montgomery Asberg Depression Rating Scale, and serum IL-6 assay using ELISA. In the depression group, subjects had lower scores in cognitive testing, than the control group (p = 0.001). Serum IL-6 was found to have a negative correlation with cognitive testing in these patients even after controlling for the severity of depressive status and Body Mass Index (BMI) (p = 0.025). MDD in elderly subjects is associated with decline in cognitive functions that may be related to peripheral IL-6 levels.

  7. Possible association of interleukin-1beta (-511C/T) and interleukin-6 ...

    African Journals Online (AJOL)

    In end stage renal disease, inflammation is considered a critical regulator of atherosclerotic plaque formation and progression, to which many dialysis and non-dialysis-related factors may contribute. Since circulating inflammatory cytokine levels vary inter-individually, one may speculate that genetic factors, such as ...

  8. Interleukin-17 contributes to the pathogenesis of autoimmune hepatitis through inducing hepatic interleukin-6 expression.

    Directory of Open Access Journals (Sweden)

    Li Zhao

    2011-04-01

    Full Text Available T helper cells that produce IL-17 (Th17 cells have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH. The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis.

  9. SERUM YKL-40 CORRELATES WITH SERUM INTERLEUKIN-6 IN MULTIPLE MYELOMA

    DEFF Research Database (Denmark)

    Mylin, Anne Kjærsgaard; Andersen, Niels Frost; Johansen, Julia S.

    2007-01-01

    Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including angiogenesis. YKL-40 expression is seeen in vascular smooth muscle cells, and the protein is suggested to function...

  10. Interleukin 6 (IL6) as a predictor outcome in patients with ...

    African Journals Online (AJOL)

    Elham Ragab

    2012-05-15

    May 15, 2012 ... IL-6 was measured by ELISA, postoperative pain (measured by Visual analog scale), hospital stay, blood loss, recovery time (return to work), and liver function tests were documented. IL-6 was significantly lowered at 6th ... This lesser degree of operative stress was also con- firmed by experimental animal ...

  11. Label-free detection of interleukin-6 using electrolyte gated organic field effect transistors.

    Science.gov (United States)

    Diacci, Chiara; Berto, Marcello; Di Lauro, Michele; Bianchini, Elena; Pinti, Marcello; Simon, Daniel T; Biscarini, Fabio; Bortolotti, Carlo A

    2017-09-27

    Cytokines are small proteins that play fundamental roles in inflammatory processes in the human body. In particular, interleukin (IL)-6 is a multifunctional cytokine, whose increased levels are associated with infection, cancer, and inflammation. The quantification of IL-6 is therefore of primary importance in early stages of inflammation and in chronic diseases, but standard techniques are expensive, time-consuming, and usually rely on fluorescent or radioactive labels. Organic electronic devices and, in particular, organic field-effect transistors (OFETs) have been proposed in the recent years as novel platforms for label-free protein detection, exploiting as sensing unit surface-immobilized antibodies or aptamers. Here, the authors report two electrolyte-gated OFETs biosensors for IL-6 detection, featuring monoclonal antibodies and peptide aptamers adsorbed at the gate. Both strategies yield biosensors that can work on a wide range of IL-6 concentrations and exhibit a remarkable limit of detection of 1 pM. Eventually, electrolyte gated OFETs responses have been used to extract and compare the binding thermodynamics between the sensing moiety, immobilized at the gate electrode, and IL-6.

  12. Vitamin D receptor protein is associated with interleukin-6 in human skeletal muscle

    Science.gov (United States)

    Vitamin D is associated with skeletal muscle physiology and function and may play a role in intramuscular inflammation, possibly via the vitamin D receptor (VDR). We conducted two studies to examine (1) whether serum 25-hydroxyvitamin D (25OHD) and/or intramuscular VDR protein concentrations are ass...

  13. Interleukin-6 upregulates paraoxonase 1 gene expression via an AKT/NF-κB-dependent pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Chi-Chih [Department of Research, Taichung Veterans General Hospital, Taichung, Taiwan (China); Hsueh, Chi-Mei [Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chen, Chiu-Yuan [Graduate Institute of Natural Healing Sciences, Nanhua University, Chiayi, Taiwan (China); Chen, Tzu-Hsiu, E-mail: hsiu@mail.chna.edu.tw [Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan (China); Hsu, Shih-Lan, E-mail: h2326@vghtc.gov.tw [Department of Research, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Applied Chemistry, National Chi Nan University, Puli, Nantou, Taiwan (China)

    2013-07-19

    Highlights: •IL-6 could induce PON1 gene expression. •IL-6 increased NF-κB protein expression and NF-κB-p50 and -p65 subunits nuclear translocation. •IL-6-induced PON1 up-regulation was through an AKT/NF-κB pathway. -- Abstract: The aim of this study is to investigate the relationship between paraoxonase 1 (PON1) and atherosclerosis-related inflammation. In this study, human hepatoma HepG2 cell line was used as a hepatocyte model to examine the effects of the pro-inflammatory cytokines on PON1 expression. The results showed that IL-6, but not TNF-α and IL-1β, significantly increased both the function and protein level of PON1; data from real-time RT-PCR analysis revealed that the IL-6-induced PON1 expression occurred at the transcriptional level. Increase of IκB kinase activity and IκB phosphorylation, and reduction of IκB protein level were also observed in IL-6-treated HepG2 cells compared with untreated culture. This event was accompanied by increase of NF-κB-p50 and -p65 nuclear translocation. Moreover, treatment with IL-6 augmented the DNA binding activity of NF-κB. Furthermore, pharmacological inhibition of NF-κB activation by PDTC and BAY 11-7082, markedly suppressed the IL-6-mediated PON1 expression. In addition, IL-6 increased the levels of phosphorylated protein kinase B (PKB, AKT). An AKT inhibitor LY294002 effectively suppressed IKK/IκB/NF-κB signaling and PON1 gene expression induced by IL-6. Our findings demonstrate that IL-6 upregulates PON1 gene expression through an AKT/NF-κB signaling axis in human hepatocyte-derived HepG2 cell line.

  14. Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

    Science.gov (United States)

    Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

  15. Interleukin-6 and interleukin-10 plasma levels and mRNA expression in polytrauma patients

    Directory of Open Access Journals (Sweden)

    Heber B. Sapan

    2017-12-01

    Conclusion: The pattern of cytokine levels in inflammation response has great impact on the outcome of polytrauma patients. Further study at the genetic level is needed to investigate inflammation process which may influence patient's outcome.

  16. Interleukin 6 (IL 6 ) as a predictor outcome in patients with ...

    African Journals Online (AJOL)

    Compensated cirrhosis means that the liver is heavily scarred but can still perform many important functions; many peoples with compensated cirrhosis have gall bladder stones. The advantages of laparoscopic cholecystectomy (LC) for most patients have been extensively published. However its benefits and successful ...

  17. Interleukin-6 and the serotonergic system of the medulla oblongata in the sudden infant death syndrome.

    Science.gov (United States)

    Rognum, Ingvar Jon; Haynes, Robin L; Vege, Ashild; Yang, May; Rognum, Torleiv O; Kinney, Hannah C

    2009-10-01

    Mild infection may trigger sudden death in the vulnerable infant by cytokine interactions with a compromised medullary serotonergic (5-HT) system, leading to disrupted cardiorespiratory regulation and sleep-related sudden death. The cytokine interleukin (IL)-6 is elevated in the cerebrospinal fluid in SIDS. We tested the hypothesis that the expression of IL-6 receptors (IL-6R) and/or gp130 (involved in IL-6R signaling) is altered in the medullary 5-HT system in SIDS. Immunohistochemistry of IL-6R and gp130 was performed on medullae from 25 SIDS infants, 20 infectious deaths, and 14 controls using a semi-quantitative grading system. In the SIDS cases, mean IL-6R intensity grade in the arcuate nucleus (major component of medullary 5-HT system) was significantly higher than in the control group (2.00 +/- 0.07 vs. 1.77 +/- 0.08, P = 0.04), with no other differences in IL-6R or gp130 expression at any other site. Arcuate 5-HT neurons expressed IL-6R, indicating a site of IL-6/5-HT interaction. In SIDS, IL-6R expression is abnormal in the arcuate nucleus, the putative human homolog of rodent ventral medullary chemosensitivity sites involving 5-HT. Aberrant interactions between IL-6 and the arcuate nucleus may contribute to impaired responses to hypercapnia generated by infection (hyper-metabolism) combined with rebreathing.

  18. Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

    Science.gov (United States)

    Afzal, Muhammad R.; Samanta, Anweshan; Xuan, Yu-Ting; Girgis, Magdy; Elias, Harold K; Zhu, Yanqing; Davani, Arash; Yang, Yanjuan; Chen, Xing; Ye, Sheng; Wang, Ou-Li; Chen, Lei; Hauptman, Jeryl; Vincent, Robert J.; Dawn, Buddhadeb

    2016-01-01

    Rationale The role of interleukin (IL)-6 in the pathogenesis of cardiac myocyte hypertrophy remains controversial. Objective To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Methods and Results Wild-type (WT) and IL-6 knockout (IL-6−/−) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6−/− mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6−/− hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiac myocytes from WT and IL-6−/− mice exposed to pro-hypertrophy agents. Furthermore, overexpression of CaMKII in H9c2 cells increased STAT3 phosphorylation, and exposure of H9c2 cells to IL-6 resulted in STAT3 activation that was attenuated by CaMKII inhibition. Together these results identify the importance of CaMKII-dependent activation of STAT3 during cardiac myocyte hypertrophy via IL-6 signaling. Conclusions Genetic deletion of IL-6 attenuates TAC-induced LV hypertrophy and dysfunction, indicating a critical role played by IL-6 in the pathogenesis of LV hypertrophy in response to pressure overload. CaMKII plays an important role in IL-6-induced STAT3 activation and consequent cardiac myocyte hypertrophy. These findings may have significant therapeutic implications for LV hypertrophy and failure in patients with hypertension. PMID:27126808

  19. Skeletal muscle interleukin-6 regulates metabolic factors in iWAT during HFD and exercise training

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet; Bertholdt, Lærke; Joensen, Ella

    2015-01-01

    OBJECTIVE: To investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism. METHODS: Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6(loxP/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD...

  20. Postoperative interleukin-6 level and early detection of complications after elective major abdominal surgery

    NARCIS (Netherlands)

    Rettig, Thijs C. D.; Verwijmeren, Lisa; Dijkstra, Ineke M.; Boerma, Djamila; Van De Garde, Ewoudt M. W.|info:eu-repo/dai/nl/304841528; Noordzij, Peter G.

    2016-01-01

    Objective: To assess the association of systemic inflammation and outcome after major abdominal surgery. Background: Major abdominal surgery carries a high postoperative morbidity and mortality rate. Studies suggest that inflammation is associated with unfavorable outcome. Methods: Levels of

  1. Role of interleukin-6 in orthodontically induced inflammatory root resorption in humans

    OpenAIRE

    Kunii, Ryuichi; Yamaguchi, Masaru; Tanimoto, Yasuhiro; Asano, Masaki; Yamada, Kunihiko; Goseki, Takemi; Kasai, Kazutaka

    2013-01-01

    Objective To determine the interleukin (IL)-6 levels in gingival crevicular fluid (GCF) of patients with severe root resorption after orthodontic treatment and investigate the effects of different static compressive forces (CFs) on IL-6 production by human periodontal ligament (hPDL) cells and the influence of IL-6 on osteoclastic activation from human osteoclastic precursor (hOCP) cells in vitro. Methods IL-6 levels in GCF samples collected from 20 patients (15 and 5 subjects without and wit...

  2. Interleukin-6 Deficiency Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutation.

    Science.gov (United States)

    Han, Yongmei; Ripley, Barry; Serada, Satoshi; Naka, Tetsuji; Fujimoto, Minoru

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive, motor neuron degenerative disease. Recent evidence indicates that inflammation is associated with many neurodegenerative diseases including ALS. Previously, abnormal levels of inflammatory cytokines including IL-1β, IL-6 and TNF-α were described in ALS patients and/or in mouse ALS models. In addition, one study showed that blocking IL-1β could slow down progression of ALS-like symptoms in mice. In this study, we examined a role for IL-6 in ALS, using an animal model for familial ALS. Mice with mutant SOD1 (G93A) transgene, a model for familial ALS, were used in this study. The expression of the major inflammatory cytokines, IL-6, IL-1β and TNF-α, in spinal cords of these SOD1 transgenic (TG) mice were assessed by real time PCR. Mice were then crossed with IL-6(-/-) mice to generate SOD1TG/IL-6(-/-) mice. SOD1 TG/IL-6(-/-) mice (n = 17) were compared with SOD1 TG/IL-6(+/-) mice (n = 18), SOD1 TG/IL-6(+/+) mice (n = 11), WT mice (n = 15), IL-6(+/-) mice (n = 5) and IL-6(-/-) mice (n = 8), with respect to neurological disease severity score, body weight and the survival. We also histologically compared the motor neuron loss in lumber spinal cords and the atrophy of hamstring muscles between these mouse groups. Levels of IL-6, IL-1β and TNF-α in spinal cords of SOD1 TG mice was increased compared to WT mice. However, SOD1 TG/IL-6(-/-) mice exhibited weight loss, deterioration in motor function and shortened lifespan (167.55 ± 11.52 days), similarly to SOD1 TG /IL-6(+/+) mice (164.31±12.16 days). Motor neuron numbers and IL-1β and TNF-α levels in spinal cords were not significantly different in SOD1 TG /IL-6(-/-) mice and SOD1 TG /IL-6 (+/+) mice. These results provide compelling preclinical evidence indicating that IL-6 does not directly contribute to motor neuron disease caused by SOD1 mutations.

  3. Early Dynamics of Interleukin-6 in Cerebrospinal Fluid after Aneurysmal Subarachnoid Hemorrhage.

    Science.gov (United States)

    Ďuriš, Kamil; Neuman, Eduard; Vybíhal, Václav; Juráň, Vilém; Gottwaldová, Jana; Kýr, Michal; Vašků, Anna; Smrčka, Martin

    2018-03-01

     Subarachnoid hemorrhage (SAH) is a severe condition associated with high mortality. Early brain injury (EBI) plays an important role in the pathophysiology of SAH, and inflammation is a major contributor to EBI. Inflammation is a widely studied topic in both experimental and clinical conditions; however, just a few clinical studies have focused primarily on the early inflammatory response after SAH, and detailed information about the association between the dynamics of early inflammatory response with main clinical characteristics is lacking. This study analyzes the early dynamics of inflammatory response after SAH and evaluates the possible associations between the markers of early inflammatory response and main clinical characteristics.  A total of 47 patients with a diagnosis of aneurysmal SAH within the last 24 hours were enrolled in the study. All treatments, including treatment of aneurysm (surgery/coiling) and implantation of a drainage system (external ventricular drainage/lumbar catheter), were conducted in the same way as in other patients with this diagnosis. Blood and cerebrospinal fluid (CSF) samples were collected three times a day for 4 days. The dynamics of proinflammatory cytokines were assessed, and associations between levels of the proinflammatory cytokines interleukin (IL)-6, IL-1β, or tumor necrosis factor (TNF)α and main clinical characteristics were evaluated using linear mixed-effect models.  The CSF levels of IL-6 were massively increased initially after SAH (up to 72 hours) with an additional increase in later phases (after 72 hours), but there was high variability in IL-6 levels. A significant association was noted between the Glasgow Outcome Scale score and both overall levels of IL-6 ( p  = 0.0095) and their dynamics ( p  = 0.0208); the effect of the Hunt and Hess scale was borderline ( p  = 0.0887). No association was found between IL-6 levels and Fisher grade, modality of treatment (surgery, coiling, no treatment), and later development of cerebral vasospasm. Plasmatic levels of IL-6 increased slightly, but no significant association was found. The levels of IL-1β and TNFα were within the physiologic range in both CSF and plasma.  Early dynamics of IL-6 in CSF are associated with a patient́s outcome. But it is difficult to use IL-6 alone for outcome prediction due to its high variability. The question is whether the dynamics of IL-6 could be used in combination with other early markers associated with brain injury. More detailed research is required to answer this question. Georg Thieme Verlag KG Stuttgart · New York.

  4. Interleukin-6 and diabetes: the good, the bad, or the indifferent?

    DEFF Research Database (Denmark)

    Kristiansen, Ole P; Mandrup-Poulsen, Thomas

    2005-01-01

    Inflammatory mechanisms play a key role in the pathogenesis of type 1 diabetes. Individuals who progress to type 2 diabetes display features of low-grade inflammation years in advance of disease onset. This low-grade inflammation has been proposed to be involved in the pathogenetic processes caus...

  5. Evaluation of the changes of interleukin- 6 level in gingival cervical fluid (GCF during orthodontic movements

    Directory of Open Access Journals (Sweden)

    Safavi SMR

    2007-06-01

    Full Text Available Background and Aim: In recent years, different substances have been considered in gingival cervical fluid (GCF as diagnostic markers due to the evaluation of biologic events and biochemical process related to bone turnover during orthodontic movements. IL-6 concentration increases in GCF during the first week after force loading. The aim of this study was to investigate the levels of IL-6 in GCF during orthodontic movements.Materials and Methods: Fourteen orthodontic patients (9 females and 5 males, mean age 15.1±2.5 years with "nCl I malocclusion needing first bicuspid extraction participated in this clinical trial. In each patient one maxillary canine was distalized (DC with a NiTi push coil spring. The contra-lateral canine (CC was included in the orthodontic appliance but was not subjected to the orthodontic force  and one of the mandibular canines was used as control with no orthodontic appliance (Antagonist canine: AC. The concentration of IL-6 was evaluated at the baseline and 14th and 28th days after intervention. GCF was taken with periopapers from both mesial and distal sides of tooth before appliance activation, on the 14th and 28th days. Concentration of IL-6 in DC, CC, and AC detected by ELISA reader was compared by repeated measure ANOVA and LSD multiple comparison, P<0.05 was considered statistically significant.Results: Although the inflammatory gingival indices increased in both DC and CC teeth but it was not significant. The amount of IL-6 in GCF increased on day 14th in DC teeth in comparison with AC and CC teeth. In addition, the concentration of IL-6 in DC teeth was significantly greater than the 1st and 28th days. The maximum concentration of IL-6 was detected in both pressure and tension sides of DCs at T14. At T28, although the IL-6 levels were significantly higher than baseline levels but, it was significantly less than T14.Conclusion: The results of this study support the hypothesis that mechanical stimuli cause an inflammatory reaction within the periodontal tissues.

  6. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B

    2004-01-01

    .001) compared to pre-stimulatory levels and controls, and a variance analysis showed significantly (P Alcohol consumption (40 g), however, did not influence plasma levels of TGF-1beta, IGF-I or IGFBP-3 in either of the two groups...... was to evaluate the circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP). METHODS: Twelve male patients with severe CP and 11 matched controls ingested 40 g alcohol. Plasma cytokine concentrations were measured for 24 h and assessed by sandwich ELISA...... techniques. RESULTS: IL-6 was higher in CP at fasting and 1, 4 and 24 h after alcohol intake (P

  7. Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans

    NARCIS (Netherlands)

    Stouthard, J. M.; van der Poll, T.; Endert, E.; Bakker, P. J.; Veenhof, C. H.; Sauerwein, H. P.; Romijn, J. A.

    1994-01-01

    Cytokines, such as tumor necrosis factor-alpha and interleukin-1 beta (IL-1 beta), alter thyroid hormone metabolism, and may be involved in the pathogenesis of the euthyroid sick syndrome. Both cytokines also induce the production of IL-6. To assess whether IL-6 itself modulates thyroid hormone

  8. Chitosan-Coated Collagen Membranes Promote Chondrocyte Adhesion, Growth, and Interleukin-6 Secretion

    Directory of Open Access Journals (Sweden)

    Nabila Mighri

    2015-11-01

    Full Text Available Designing scaffolds made from natural polymers may be highly attractive for tissue engineering strategies. We sought to produce and characterize chitosan-coated collagen membranes and to assess their efficacy in promoting chondrocyte adhesion, growth, and cytokine secretion. Porous collagen membranes were placed in chitosan solutions then crosslinked with glutaraldehyde vapor. Fourier transform infrared (FTIR analyses showed elevated absorption at 1655 cm-1 of the carbon–nitrogen (N=C bonds formed by the reaction between the (NH2 of the chitosan and the (C=O of the glutaraldehyde. A significant peak in the amide II region revealed a significant deacetylation of the chitosan. Scanning electron microscopy (SEM images of the chitosan-coated membranes exhibited surface variations, with pore size ranging from 20 to 50 µm. X-ray photoelectron spectroscopy (XPS revealed a decreased C–C groups and an increased C–N/C–O groups due to the reaction between the carbon from the collagen and the NH2 from the chitosan. Increased rigidity of these membranes was also observed when comparing the chitosan-coated and uncoated membranes at dried conditions. However, under wet conditions, the chitosan coated collagen membranes showed lower rigidity as compared to dried conditions. Of great interest, the glutaraldehyde-crosslinked chitosan-coated collagen membranes promoted chondrocyte adhesion, growth, and interleukin (IL-6 secretion. Overall results confirm the feasibility of using designed chitosan-coated collagen membranes in future applications, such as cartilage repair.

  9. Tenascin C upregulates interleukin-6 expression in human cardiac myofibroblasts via toll-like receptor 4.

    Science.gov (United States)

    Maqbool, Azhar; Spary, Emma J; Manfield, Iain W; Ruhmann, Michaela; Zuliani-Alvarez, Lorena; Gamboa-Esteves, Filomena O; Porter, Karen E; Drinkhill, Mark J; Midwood, Kim S; Turner, Neil A

    2016-05-26

    To investigate the effect of Tenascin C (TNC) on the expression of pro-inflammatory cytokines and matrix metalloproteinases in human cardiac myofibroblasts (CMF). CMF were isolated and cultured from patients undergoing coronary artery bypass grafting. Cultured cells were treated with either TNC (0.1 μmol/L, 24 h) or a recombinant protein corresponding to different domains of the TNC protein; fibrinogen-like globe (FBG) and fibronectin type III-like repeats (TNIII 5-7) (both 1 μmol/L, 24 h). The expression of the pro-inflammatory cytokines; interleukin (IL)-6, IL-1β, TNFα and the matrix metalloproteinases; MMPs (MMP1, 2, 3, 9, 10, MT1-MMP) was assessed using real time RT-PCR and western blot analysis. TNC increased both IL-6 and MMP3 (P < 0.01) mRNA levels in cultured human CMF but had no significant effect on the other markers studied. The increase in IL-6 mRNA expression was mirrored by an increase in protein secretion as assessed by enzyme-linked immunosorbant assay (P < 0.01). Treating CMF with the recombinant protein FBG increased IL-6 mRNA and protein (P < 0.01) whereas the recombinant protein TNIII 5-7 had no effect. Neither FBG nor TNIII 5-7 had any significant effect on MMP3 expression. The expression of toll-like receptor 4 (TLR4) in human CMF was confirmed by real time RT-PCR, western blot and immunohistochemistry. Pre-incubation of cells with TLR4 neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mRNA and protein expression. TNC up-regulates IL-6 expression in human CMF, an effect mediated through the FBG domain of TNC and via the TLR4 receptor.

  10. Early life socioeconomic status associates with interleukin-6 responses to acute laboratory stress in adulthood.

    Science.gov (United States)

    Lockwood, Kimberly G; John-Henderson, Neha A; Marsland, Anna L

    2018-05-01

    It is proposed that environmental exposures in early life influence immune programming. Specifically, socioeconomic disadvantage is thought to program an immune phenotype that is prone to inflammation and associated with increased risk for inflammatory disease later in life. Existing literature shows an inverse association of early childhood socioeconomic status (SES) with adult levels of systemic inflammation. Here, we extend that literature to examine whether early childhood SES also relates to the magnitude of inflammatory response to acute psychological stress in adulthood. Healthy volunteers (N = 110; 40-58 years; 59% female; 90% white) performed a laboratory stress protocol, with blood samples drawn at the end of a 30-min baseline, a 5-min speech task, and a 30-min recovery to assess interleukin (IL)-6 stress responses. An early childhood SES index was derived from reports of parental home and vehicle ownership, and number of bedrooms per child in the home across ages 1-2, 3-4, and 5-6. Regressions adjusted for current age, sex, race, and BMI showed that lower SES at age 1-2 was associated with larger IL-6 stress responses in adulthood (ΔR 2  = 0.05, β = -0.24, p = .03). This association was independent of adult SES and task-evoked affective responses. No association was found between SES at ages 3-4 or 5-6 and IL-6 responses. These results provide initial evidence for a link between disadvantage in the first 2 years of life and heightened inflammatory response to stress in adulthood; this link may contribute to the increased disease risk that accompanies being raised in disadvantaged socioeconomic circumstances. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Association between metabolic disturbances and G-174C polymorphism of interleukin-6 gene in obese children

    Directory of Open Access Journals (Sweden)

    Pyrzak B

    2009-12-01

    Full Text Available Abstract Objective The aim of the study was to investigate whether the G-174C polymorphism of the IL-6 gene is related to obesity and the incidence of the metabolic syndrome (MetS according to IDF definition in children. Materials and methods The examined group included 124 obese children with BMI ≥ 2 SDS, and the control group consisted of 56 non-obese children with BMI Results In the obese children, carriers of C allele in homozygotic and heterozygotic genotypes were more frequent than in the control group. The carriers of C alleles presented with lower thickness of subcutaneous tissue and higher concentrations of HDL-C than the wild type. The incidence of MetS was 33% of the group of obese children. Analysis of the presence of MetS factors showed that there is more frequent MetS in the group with the wild homozygous genotype type. Conclusion Polymorphism 174G > C in the IL-6 gene does not seem to be associated with obesity and with the incidence of MetS in children.

  12. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B

    2004-01-01

    BACKGROUND: Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evalu......BACKGROUND: Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study...

  13. Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Thomsen, Maria; Kersten, Christian; Sorbye, Halfdan

    2016-01-01

    Objectives: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status. Results...... 24.3 months to 12.3 months, (P treatment serum samples...... from 393 patients included in the NORDIC-VII trial, in which patients with mCRC received first line treatment. The effect of serum IL-6 and CRP on progressionfree survival (PFS) and overall survival (OS) was estimated. Conclusions: High baseline serum consentrations of IL-6 or CRP were associated...

  14. Association between serum interleukin-6 and serum 3,5,3'-triiodothyronine in nonthyroidal illness

    NARCIS (Netherlands)

    Boelen, A.; Platvoet-ter Schiphorst, M. C.; Wiersinga, W. M.

    1993-01-01

    Increased serum concentrations of FFA, bilirubin, and carboxyl-methyl-propyl-furanpropionic acid, accumulating in chronic renal failure in direct relationship with serum creatinine, have all been implicated in the pathogenesis of the low T3 syndrome during illness. Cytokines may also be involved in

  15. Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma.

    Science.gov (United States)

    Naik, Srilata Puru; P A, Mahesh; B S, Jayaraj; Madhunapantula, SubbaRao V; Jahromi, Sarah Raeiszadeh; Yadav, Manish Kumar

    2017-08-01

    Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p asthma (p asthma duration, total IgE, AEC, number of allergens sensitized and degree of sensitization. No significant correlation (p > 0.5) was observed with IL-6 and MMP-9 levels and FEV 1 improvement after 2 months of ICS+LABA. Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions.

  16. Correction of abnormal B-cell subset distribution by interleukin-6 receptor blockade in polymyalgia rheumatica.

    Science.gov (United States)

    Carvajal Alegria, Guillermo; Devauchelle-Pensec, Valérie; Renaudineau, Yves; Saraux, Alain; Pers, Jacques-Olivier; Cornec, Divi

    2017-08-01

    The aim was to study lymphocyte subsets and circulating cytokines at diagnosis of PMR and after tocilizumab monotherapy. Eighteen untreated patients with PMR were included in a prospective study and received 3-monthly tocilizumab infusions without glucocorticoids. Lymphocyte subset distribution was assessed by flow cytometry and serum cytokines were assayed by a 34-cytokine array and ELISA, at baseline and during follow-up. Baseline data were also compared with age- and sex-matched controls. At baseline, total lymphocytes, T-cell subsets and NK cell counts were similar in patients and controls, but patients had significantly lower B-cell counts attributable to lower transitional, naïve and post-switch memory B-cell subsets. Circulating B-cell counts were positively correlated with the PMR activity score (PMR-AS) in untreated active patients at baseline, but subsequently increased to normal values while disease activity was controlled after tocilizumab therapy. Among serum cytokines, IL-6 showed the largest concentration difference between patients and controls, and the serum IL-6 concentration was correlated with baseline PMR-AS. The effects of tocilizumab on serum IL-6 concentration were heterogeneous, and the patients whose serum IL-6 decreased after tocilizumab therapy exhibited a significant increase in circulating B-cell counts. In patients with PMR, B-cell lymphopenia and abnormal B-cell subset distribution are associated with disease activity and IL-6 concentration, and both are corrected by the IL-6 antagonist tocilizumab. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  17. Interleukin-6 and tumor necrosis factor-alpha gene polymorphisms in chronic idiopathic urticaria.

    Science.gov (United States)

    Tavakol, M; Amirzargar, A A; Movahedi, M; Aryan, Z; Bidoki, A Z; Gharagozlou, M; Aghamohammadi, A; Nabavi, M; Ahmadvand, A; Behniafard, N; Heidari, K; Soltani, S; Rezaei, N

    2014-01-01

    This study was performed to evaluate association of gene polymorphisms among proinflammatory cytokines and susceptibility to chronic idiopathic urticaria (CIU). Ninety patients with prolonged urticaria more than 6 weeks were included as case group. Single nucleotide polymorphisms (SNPs) of IL-6 (G/C -174, G/A nt565) and TNF-α (G/A -308, G/A -238) were evaluated, using polymerase chain reaction (PCR); and the results were compared to the control group. G allele was significantly higher in the patients at locus of -238 of promoter of TNF-α gene (p<0.001). Frequency of following genotypes were significantly lower in patients with CIU, compared to controls: AG at -308 and GA at -238 of TNF-α gene (p<0.05 and p<0.001, respectively), CG at -174 and GG at +565 of IL-6 gene (p<0.05). Additionally, following genotypes were more common among patients with CIU: GG at -308 and -238 of TNF-α gene (p<0.05 and p<0.001, respectively), GG at -174 and GA at +565 of IL-6 gene (p<0.05). Pro-inflammatory cytokine gene polymorphisms can affect susceptibility to CIU. TNF-α promoter polymorphisms as well as IL-6 gene polymorphisms are associated with CIU. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  18. Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation.

    Science.gov (United States)

    Dahlgren, Jovanna; Samuelsson, Anne-Maj; Jansson, Thomas; Holmäng, Agneta

    2006-08-01

    Maternal systemic infection during pregnancy may expose the fetus to infectious agents and high levels of mediators of the resulting inflammatory response, such as IL-6 (IL-6). Increased fetal and maternal levels of IL-6 have been associated with adverse neonatal outcome but might also stress the fetus and contribute to cardiovascular and neuroendocrine dysfunction in adulthood. It is unclear whether interleukins cross the placental barrier, although this matter has been little studied. The aim of this study was therefore to investigate if IL-6 administered to pregnant rats in vivo is transferred to the fetus. We injected 125I IL-6 i.v. to pregnant dams at gestation day 11-13 (mid-gestation) or 17-19 (late gestation). We found 125I-IL-6 in the exposed fetuses as well as in amniotic fluids. Fetal 125I-IL-6 levels were markedly higher in animals injected in mid-gestation compared with late pregnancy (p materno-fetal clearance for 125I-IL-6 in mid-gestation (p fetal injury but also stimulate the release of fetal stress hormones resulting in stimuli or insults in neuroendocrine structures and hormonal axes which might lead to disease at adult age.