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Sample records for serum interleukin-6 il-6

  1. Increased expression of interleukin-6 (IL-6) gene transcript in relation to IL-6 promoter hypomethylation in gingival tissue from patients with chronic periodontitis.

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    Kobayashi, Tetsuo; Ishida, Kohei; Yoshie, Hiromasa

    2016-09-01

    DNA methylation of the cytokine genes may play a role in the pathogenesis of periodontitis. The aim of this study is to evaluate whether the alteration of interleukin-6 (IL-6) gene promoter methylation in the gingival tissue (GT) and peripheral blood (PB) is unique to chronic periodontitis (CP). DNA isolated from the GT and PB of 25 patients with (CP) and 20 healthy controls (H) was modified with sodium bisulfite and analyzed for IL-6 promoter methylation with direct sequencing. The levels of IL-6 mRNA and serum IL-6 protein were evaluated by a quantitative reverse transcription polymerase chain reaction and an enzyme-linked immunosorbent assay. The CP group showed that the overall methylation rates of IL-6 promoter that contained 19 cytosine-guanine dinucleotide (CpG) motifs were significantly decreased in GT in comparison to PB (p<0.001), which was significantly negatively correlated with the probing depth (p=0.003). The GT and PB of the H group displayed similar overall methylation rates. No significant difference was observed in the methylation rates at each CpG in GT in comparison to the PB in both groups. The levels of IL-6 mRNA in the GT and PB and serum IL-6 of the two groups were comparable. The ratio of IL-6 mRNA in the GT relative to the PB was significantly higher in the CP group than in the H group (p=0.03). The increased expression of IL-6 gene transcription may be related to IL-6 promoter hypomethylation in the GT from CP patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. 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

  3. 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.

  4. Hypoxemia increases serum interleukin-6 in humans

    DEFF Research Database (Denmark)

    Klausen, T; Olsen, Niels Vidiendal; Poulsen, T D

    1997-01-01

    Serum concentrations of interleukin (IL) 1 beta, IL-1 receptor antagonist (IL-1ra), IL-6, tumor necrosis factor (TNF) alpha, and C-reactive protein (CRP) were determined in ten healthy men at sea level and during four days of altitude hypoxia (4350m above sea level). The mean (SD) arterial blood...

  5. Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6

    DEFF Research Database (Denmark)

    Keller, Pernille; Penkowa, Milena; Keller, Charlotte

    2005-01-01

    Contracting muscle fibers produce and release IL-6, and plasma levels of this cytokine are markedly elevated in response to physical exercise. We recently showed autocrine regulation of IL-6 in human skeletal muscle in vivo and hypothesized that this may involve up-regulation of the IL-6 receptor....... Infusion of rhIL-6 to humans had no effect on the mRNA level of the IL-6 receptor, whereas there was an increase at the protein level. IL-6 receptor mRNA increased similarly in muscle of both IL-6 KO mice and wild-type mice in response to exercise. In conclusion, exercise increases IL-6 receptor production....... Therefore, we investigated IL-6 receptor regulation in response to exercise and IL-6 infusion in humans. Furthermore, using IL-6-deficient mice, we investigated the role of IL-6 in the IL-6 receptor response to exercise. Human skeletal muscle biopsies were obtained in relation to: 3 h of bicycle exercise...

  6. Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the neonatal mouse brain: possible role for IL-6 trans-signaling in brain development and functional neurobehavioral outcomes.

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    Brunssen, Susan H; Moy, Sheryl S; Toews, Arrel D; McPherson, Christopher A; Harry, G Jean

    2013-01-01

    Adverse neurodevelopmental outcomes are linked to perinatal production of inflammatory mediators, including interleukin 6 (IL-6). While a pivotal role for maternal elevation in IL-6 has been established in determining neurobehavioral outcomes in the offspring and considered the primary target mediating the fetal inflammatory response, questions remain as to the specific actions of IL-6 on the developing brain. CD-1 male mice received a subdural injection of the bioactive fusion protein, hyper IL-6 (HIL-6) on postnatal-day (PND)4 and assessed from preweaning until adulthood. Immunohistochemical evaluation of astrocytes and microglia and mRNA levels for pro-inflammatory cytokines and host response genes indicated no evidence of an acute neuroinflammatory injury response. HIL-6 accelerated motor development and increased reactivity to stimulation and number of entries in a light/dark chamber, decreased ability to learn to withhold a response in passive avoidance, and effected deficits in social novelty behavior. No changes were observed in motor activity, pre-pulse startle inhibition, or learning and memory in the Morris water maze or radial arm maze, as have been reported for models of more severe developmental neuroinflammation. In young animals, mRNA levels for MBP and PLP/DM20 decreased and less complexity of MBP processes in the cortex was evident by immunohistochemistry. The non-hydroxy cerebroside fraction of cerebral lipids was increased. These results provide evidence for selective effects of IL-6 signaling, particularly trans-signaling, in the developing brain in the absence of a general neuroinflammatory response. These data contribute to our further understanding of the multiple aspects of IL-6 signaling in the developing brain. Published by Elsevier Inc.

  7. Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6

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    Yan Jin

    2012-01-01

    Full Text Available Abstract Background Migraine headache is one of the most common neurological disorders, but the pathophysiology contributing to migraine is poorly understood. Intracranial interleukin-6 (IL-6 levels have been shown to be elevated during migraine attacks, suggesting that this cytokine may facilitate pain signaling from the meninges and contribute to the development of headache. Methods Cutaneous allodynia was measured in rats following stimulation of the dura with IL-6 alone or in combination with the MEK inhibitor, U0126. The number of action potentials and latency to the first action potential peak in response to a ramp current stimulus as well as current threshold were measured in retrogradely-labeled dural afferents using patch-clamp electrophysiology. These recordings were performed in the presence of IL-6 alone or in combination with U0126. Association between ERK1 and Nav1.7 following IL-6 treatment was also measured by co-immunoprecipitation. Results Here we report that in awake animals, direct application of IL-6 to the dura produced dose-dependent facial and hindpaw allodynia. The MEK inhibitor U0126 blocked IL-6-induced allodynia indicating that IL-6 produced this behavioral effect through the MAP kinase pathway. In trigeminal neurons retrogradely labeled from the dura, IL-6 application decreased the current threshold for action potential firing. In response to a ramp current stimulus, cells treated with IL-6 showed an increase in the numbers of action potentials and a decrease in latency to the first spike, an effect consistent with phosphorylation of the sodium channel Nav1.7. Pretreatment with U0126 reversed hyperexcitability following IL-6 treatment. Moreover, co-immunoprecipitation experiments demonstrated an increased association between ERK1 and Nav1.7 following IL-6 treatment. Conclusions Our results indicate that IL-6 enhances the excitability of dural afferents likely via ERK-mediated modulation of Nav1.7 and these responses

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

    International Nuclear Information System (INIS)

    Kayaalti, Zeliha; Tekin, Deniz; Aliyev, Vugar; Yalcin, Serap; Kurtay, Guelay; Soeylemezoglu, Tuelin

    2011-01-01

    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: → We studied between the association of IL-6 polymorphism and metal levels in the placenta tissues. → It was the first report evaluating the association

  9. 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

  10. 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

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

    Science.gov (United States)

    Ciejka, Elżbieta; Skibska, Beata; Gorąca, Anna

    2017-06-27

    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. 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. 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). 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. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  12. The accuracy of serum interleukin-6 and tumour necrosis factor as markers for ovarian torsion.

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    Cohen, S B; Wattiez, A; Stockheim, D; Seidman, D S; Lidor, A L; Mashiach, S; Goldenberg, M

    2001-10-01

    The aim of this study was to investigate a possible role for interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) as pre-operative markers for the diagnosis of ovarian torsion. Twenty consecutive patients admitted to the gynaecological emergency room with suspected clinical diagnosis of ovarian torsion were prospectively assigned to the study. Blood samples were drawn pre-operatively and examined for serum concentrations of IL-6 and TNF-alpha. Surgeons were blinded to laboratory results prior to laparoscopy. The pre-operative diagnosis of ovarian torsion was confirmed during an urgent diagnostic laparoscopy in 8 (40%) patients. The surgical diagnosis among the remaining 12 patients was a large ovarian cyst not in torsion. In six out of eight (75.0%) patients with ovarian torsion serum IL-6 concentrations were elevated. None of the 12 patients without torsion had elevated serum IL-6 concentrations. This difference was statistically significant (P < 0.001). There was no significant difference in the proportion of women with elevated serum TNF-alpha concentrations, two of eight (25.0%) patients with torsion and four of 12 (33.3%) control cases. Elevated serum IL-6 concentrations, but not serum TNF-alpha concentrations, were significantly associated with the occurrence of ovarian torsion. In patients with vague clinical signs of ovarian torsion, serum IL-6 might help to distinguish which patients should undergo diagnostic laparoscopy.

  13. Clinical significance of changes of serum gas, IL-6 and IL-10 levels after treatment in patients with peptic ulcer

    International Nuclear Information System (INIS)

    Ye Yuexian

    2009-01-01

    Objective: To explore the clinical significance of changes of serum Gas, Interleukin-6(IL-6) and Interleukin-10(IL-10) levels in patients with peptic ulcer. Methods: Serum Gas, IL-6 and IL-10 (with RIA) levels were determined in 61 patients with peptic ulcer both before and after treatment as well as in 35 controls. Results: Before treatment the serum Gas, IL-6 and IL-10 levels were significantly higher in the patients with peptic ulcer than those in controls (P 0.05). Conclusion: Serum Gas, IL-6 and IL-10 levels were closely related to the diseases process of peptic ulcer and were of prognostic values. (authors)

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

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    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.

  15. 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.

  16. A study of interleukin 6 (IL-6 and tumor necrosis factor alpha (TNF-α serum levels in rats subjected to fecal peritonitis and treated with intraperitoneal ropivacaine Avaliação dos níveis séricos de interleucina 6 (IL-6 e fator de necrose tumoral (TNF-α em ratos submetidos a peritonite fecal e tratado com ropivacaína intraperitoneal

    Directory of Open Access Journals (Sweden)

    Marcos Célio Brocco

    2012-07-01

    Full Text Available PURPOSE: The objective of this study was to assess the cytokine serum levels of IL-6 and TNF-α in rats subjected to fecal peritonitis and treated with peritoneal lavage with 0.2% ropivacaine by peritoneal lavage. METHODS: We subjected 16 Wistar rats to laparotomy 6 hours after the induction of fecal peritonitis with autogenous stool and subsequently divided the rats randomly into 4 groups: I-control, no treatment; II- drying of the abdominal cavity; III- lavage of the abdominal cavity with 3 mL of 0.9% normal saline and drying; IV- lavage of the abdominal cavity with 3 mL of 0.2% ropivacaine and drying. Six hours following the laparotomy, the animals underwent cardiac puncture, and 1 mL of blood was collected for cytokine assessment before the animals were euthanized. RESULTS: The lavage with ropivacaine resulted in smaller TNF-α levels compared with those observed in the other treatment groups (p 0.05 between groups III and IV. CONCLUSION: Peritoneal lavage with 0.2% ropivacaine was shown to reduce plasma levels of IL-6 and TNF-α in the treatment of fecal peritonitis in rats.OBJETIVO: O objetivo do presente estudo foi avaliar as dosagens séricas das citocinas Il-6 e TNF-α em ratos submetidos à peritonite fecal e tratados com lavagem peritoneal com ropivacaína a 0,2%. MÉTODOS: Utilizaram-se 16 ratos Wistar, submetidos à laparotomia 6 horas após a indução de peritonite fecal com fezes autógenas, distribuídos aleatoriamente em 4 grupos: I- Controle, nenhum tratamento; II- Enxugamento da cavidade abdominal; III- Lavagem da cavidade abdominal com 3 ml de solução salina 0,9% e enxugamento; IV- Lavagem da cavidade abdominal com 3 ml de ropivacaína a 0,2% e enxugamento. Seis horas após a laparotomia os animais foram submetidos à punção cardíaca com retirada de 1 mL de sangue para a dosagem das citocinas e, a seguir, eutanasiados. RESULTADOS: A lavagem com ropivacaína apresentou valores de TNF-α menores do que os observados com

  17. Development of a quick serum IL-6 measuring system in rheumatoid arthritis.

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    Koyama, Kensuke; Ohba, Tetsuro; Ishii, Kentaro; Jung, Giman; Haro, Hirotaka; Matsuda, Kenichi

    2017-07-01

    Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of rheumatoid arthritis (RA). Both fulfillment of remission criteria and assessment of other methods of evaluation of RA are important for preventing joint damage progression. Measurement of serum IL-6 concentrations has been reported to be useful for monitoring RA disease activity. However, it takes at least 4-5h to measure serum IL-6 concentrations using traditional methods, which limits its utility during routine assessment in daily clinical practice settings. We established a novel method that enables measurement of serum IL-6 within 24min and requires a very small blood volume. We investigated the accuracy and efficacy of this system in RA patients. One hundred fifty blood samples collected from 76 patients were measured using the two systems. We first developed the prototype of the Human IL-6 RAYFAST. Then, we examined the correlation between the prototype RAYFAST and chemiluminescent enzyme immunoassay (CLEIA) methods. Finally, we compared IL-6 concentrations and clinical parameters using both systems. The correlation between RAYFAST (x) and CLEIA (y) for IL-6 was y=0.895x-5.94, r=0.941 (p<0.0001). Serum IL-6 concentrations in RAYFAST correlated with DAS28-CRP (r=0.372, p<0.05) and DAS28-ESR (r=0.397, p<0.01). Serum IL-6 concentrations in CLEIA correlated with DAS28-CRP (r=0.313, p<0.001) and DAS28-ESR (r=0.353, p<0.001). This new cytokine quick measure system is as accurate as CLEIA methods. Serum IL-6 concentrations can be measured in 24min using the prototype RAYFAST. It might be usable in the daily clinical practice setting, thereby contributing to improved RA management. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Clinical study of serum interleukin-6 in children with community-acquired pneumonia

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    Ahmed A. Khattab

    2018-06-01

    Full Text Available Background: Community-acquired pneumonia (CAP is an important childhood killer. Excessive production of cytokines, including interleukin-6 (IL-6, might be associated with severe disease course but pediatric data is limited. Aim: To assess value of IL-6 in predicting CAP severity in children. Methods: A prospective study conducted on 73 children hospitalized for CAP and 15 healthy controls. Pneumonia severity was evaluated according to World Health Organization (WHO classification, Respiratory Index of Severity Score (RISC, Predisposition, Insult, Response, Organ dysfunction modified (PIROm score, and Pediatric Respiratory Severity Score (PRESS. Serum IL-6 was measured within 24 h of admission. The primary outcome was occurrence of any pneumonia complications or death within 30 days. Results: IL-6 was significantly higher among patients compared with controls. Unlike CRP, IL-6 was significantly higher among children with severe pneumonia as determined by WHO, PRESS, and RISC (p = 0.001 for all. IL-6 was significantly higher among children with PICU admission, mechanical ventilation, shock (p = 0.001 for all, hypoxia (p < 0.001, and lobar consolidation (p = 0.042. IL-6 had positive correlations with PRESS (rs=0.8, P < 0.001, RISC (rs=0.6, p < 0.001, and PIROm (rs=0.59, p < 0.001 while a negative correlation was found with Oxygen saturation [r = −0.61, p = 0.001]. IL-6 was not significantly correlated with CRP. Receiver Operating Characteristic curve (ROC analysis revealed large area under the curve (AUC of IL-6 for prediction of severe pneumonia as classified by WHO, PRESS, and RISC (AUC = 0.95, 0.94, and 0.89 respectively. Conclusion: IL-6 appears to be valuable for assessment of CAP severity in children compared with conventional biomarkers. Keywords: Interleukin-6, Community acquired pneumonia, C-reactive protein, Prognosis, Pediatric

  20. Serum IL-6 level and associated factors: hemodialysis patients

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    Seifi S, Mokhtari A

    2008-07-01

    Full Text Available "nBackground: The annual amount of mortality in ESRD exceeds the expectation and represents the recent evidences of the inflammation as its etiology. The etiology of inflammation is not clearly known. Chronic inflammation is a dominant occurrence of ESRD which increases the risk of atherosclerosis, malnutrition and peripheral vascular disease. Inflammatory responses are orchestrated by cytokines. Some of the proinflammatory cytokines like IL-6 have a crucial role in this phenomenon. The IL-6 and its receptor activity is up regulated in ESRD patients and the increased level of IL-6 predicts cardiovascular mortality and morbidity in normal and CRF patients. This study devotes itself to determining the serum level of IL-6 and factors affecting it in patients undergoing chronic hemodialysis in Imam Khomeini Hospital which can represent the Iranian Society. By identifying factors affecting the serum level of IL-6 and high-risk patients we can provide treatment possibilities, a decrease in mortality and an improvement in its prognosis. "n"nMethods: In this study 42 patients in Imam Dialysis Center were chosen and their serum IL-6 levels were measured at 2 times at three month interval and at the same time blood sample analysis were done for the following: Alb CPR, Ca, P, PTH, TIBC, Ferritin, TG, Chol, LDL, HDL, Uric Acid, Hb, WBC and urea."n"nResults: The mean serum level of IL-6 in hemodialysis patients was 6.35±4.47pg/ml (minimum: 0.55, maximum: 18.25 with the normal range of 1.3±3.2pg/ml."n"nConclusions: The IL-6 level was higher than normal range in the 52% of the patients. The serum IL-6 level had a significant correlations with CPR, Ferritin, TIBC, WBC and their serum IL-6 level was significantly higher in patients with hypertension, but no significant correlation was observed between other parameters and IL-6

  1. 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.

  2. Normal mitogen-induced suppression of the interleukin-6 (IL-6) response and its deficiency in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Warrington, R.J.; Rutherford, W.J.

    1990-01-01

    A low-frequency suppressor-cell population in normal peripheral blood inhibits the B-cell CESS response to IL-6, following pokeweed mitogen stimulation. The suppression of IL-6 responsiveness is radiation sensitive, directed against CESS targets and not mediated by inhibition of IL-6 production, and associated with nonspecific cytotoxic activity against CESS targets. The generation of these cytolytic cells is also radiation sensitive. A correlation was found between PWM-induced cytotoxicity against CESS and the suppression of IL-6-dependent IgG production. But cytotoxicity toward CESS targets is not responsible for this suppression because IL-2 induces equivalent or greater nonspecific cytotoxicity against CESS in the total absence of suppression of CESS-derived IgG production and suppression is also induced by mitogen-activated PBL separated from CESS targets by a cell-impermeable membrane. This suppression was not mediated by TNF alpha/beta or IFN-gamma. In systemic lupus erythematosus, suppression of IL-6-dependent IgG production is impaired in patients with active disease (29.2 +/- 13.7%) compared to patients with inactive disease (70 +/- 19.5%) or normal controls (82.8 +/- 9.2%). There is also a defect in mitogen-induced nonspecific cytotoxicity in active SLE (specific lysis 15.1 +/- 3.5%, compared to 34 +/- 4% in normals). Pokeweed mitogen-activated PBL can therefore normally induce suppression of B-cell IL-6 responses and this response is deficient in lupus

  3. Relations Between Serum Essential Fatty Acids, Cytokines (IL-6 & IL ...

    African Journals Online (AJOL)

    The aim of this study was to investigate the relations between free radical generation, interleukins (IL-6 & IL-8), apoptotic marker soluble Fas (sFas), and the level of ... IL-6, IL-8 and sFas whereas serum fatty acid revealed that Linoleicacid (LA) and alpha linolenic acid (ALA) were significantly decreased in the studied cases .

  4. Influence of correlation between HLA-G polymorphism and Interleukin-6 (IL6) gene expression on the risk of schizophrenia.

    Science.gov (United States)

    Shivakumar, Venkataram; Debnath, Monojit; Venugopal, Deepthi; Rajasekaran, Ashwini; Kalmady, Sunil V; Subbanna, Manjula; Narayanaswamy, Janardhanan C; Amaresha, Anekal C; Venkatasubramanian, Ganesan

    2018-07-01

    Converging evidence suggests important implications of immuno-inflammatory pathway in the risk and progression of schizophrenia. Prenatal infection resulting in maternal immune activation and developmental neuroinflammation reportedly increases the risk of schizophrenia in the offspring by generating pro-inflammatory cytokines including IL-6. However, it is not known how prenatal infection can induce immuno-inflammatory responses despite the presence of immuno-inhibitory Human Leukocyte Antigen-G (HLA-G) molecules. To address this, the present study was aimed at examining the correlation between 14 bp Insertion/Deletion (INDEL) polymorphism of HLA-G and IL-6 gene expression in schizophrenia patients. The 14 bp INDEL polymorphism was studied by PCR amplification/direct sequencing and IL-6 gene expression was quantified by using real-time RT-PCR in 56 schizophrenia patients and 99 healthy controls. We observed significantly low IL6 gene expression in the peripheral mononuclear cells (PBMCs) of schizophrenia patients (t = 3.8, p = .004) compared to the controls. In addition, schizophrenia patients carrying Del/Del genotype of HLA-G 14 bp INDEL exhibited significantly lower IL6 gene expression (t = 3.1; p = .004) than the Del/Ins as well as Ins/Ins carriers. Our findings suggest that presence of "high-expressor" HLA-G 14 bp Del/Del genotype in schizophrenia patients could attenuate IL-6 mediated inflammation in schizophrenia. Based on these findings it can be assumed that HLA-G and cytokine interactions might play an important role in the immunological underpinnings of schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Serum levels of interleukin 6 in schizophrenic patients during treatment augmentation with sarcosine (results of the PULSAR study).

    Science.gov (United States)

    Strzelecki, Dominik; Urban-Kowalczyk, Małgorzata; Wysokiński, Adam

    2018-03-01

    Augmentation of sarcosine, a natural inhibitor of the glycine transporter type I, normalizes glutamatergic neurotransmission, having beneficial impact on primary negative symptoms in schizophrenia and may also influence immune system and interleukin 6 (IL-6) levels. Finding a relationship between initial IL-6 serum concentrations or its changes and severity of symptoms as a result of sarcosine addition to stable antipsychotic treatment. Fifity-eight individuals with schizophrenia with predominantly negative symptoms completed a 6-month randomized, double-blind placebo-controlled prospective study. Patients received 2 g of sarcosine (n = 29) or placebo (n = 30) daily per os. We measured IL-6 levels and severity of symptoms at the beginning, after 6 weeks and 6 months. As main clinical tools, we used Positive and Negative Syndrome Scale (PANSS) and Calgary depression scale for schizophrenia (CDSS). Augmentation with sarcosine had no effect on IL-6 serum levels in all time points. We noted significant improvements in negative symptoms, general psychopathology, and total PANSS score in the sarcosine group. We found correlation of initial serum IL-6 with severity of positive symptoms and negative association between IL-6 levels reduction and positive symptoms reduction. Sarcosine does not significantly affect IL-6 concentrations but IL-6 may be involved in mechanisms related to the presence of positive symptoms. Copyright © 2018 John Wiley & Sons, Ltd.

  6. 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

  7. Association between serum interleukin-6 concentrations and mortality in older adults: the Rancho Bernardo study.

    Directory of Open Access Journals (Sweden)

    Jeffrey K Lee

    Full Text Available Interleukin-6 (IL-6 may have a protective role in acute liver disease but a detrimental effect in chronic liver disease. It is unknown whether IL-6 is associated with risk of liver-related mortality in humans.To determine if IL-6 is associated with an increased risk of all-cause, cardiovascular disease (CVD, cancer, and liver-related mortality.A prospective cohort study included 1843 participants who attended a research visit in 1984-87. Multiple covariates were ascertained including serum IL-6. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous (log transformed variable with all-cause, CVD, cancer, and liver-related mortality. Patients with prevalent CVD, cancer and liver disease were excluded for cause-specific mortality.The mean (± standard deviation age and body-mass-index (BMI of participants was 68 (± 10.6 years and 25 (± 3.7 Kg/m(2, respectively. During the 25,802 person-years of follow-up, the cumulative all-cause, CVD, cancer, and liver-related mortality were 53.1% (N = 978, 25.5%, 11.3%, and 1.3%, respectively. The median (± IQR length of follow-up was 15.3 ± 10.6 years. In multivariable analyses, adjusted for age, sex, alcohol, BMI, diabetes, hypertension, total cholesterol, HDL, and smoking, one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause, CVD, cancer, and liver-related mortality, with hazard ratios of 1.48 (95% CI, 1.33-1.64, 1.38 (95% CI, 1.16-1.65, 1.35 (95% CI, 1.02-1.79, and 1.88 (95% CI, 0.97-3.67, respectively. CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant, independent of CRP levels.In community-dwelling older adults, serum IL-6 is associated with all-cause, CVD, cancer, and liver-related mortality.

  8. Effect of flurbiprofen aretilon on serum hs-CRP, IL-6 levels in patients undergoing esophageal cancer surgery

    International Nuclear Information System (INIS)

    Li Jiakai

    2011-01-01

    Objective: To investigate the effect of flurbiprofen axetil on serum high sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6) in the patients undergoing esophageal cancer surgery. Methods: Thirty patients were divided into 2 groups with 15 cases each. The patients in groups A were given flurbiprofen axetil and those in group B were not as the controls. Serum hs-CRP (immuno-turbidity method) and IL-6 (RIA) levels were determined before anesthesia induction and after extubation. Results: The levels of serum hs-CRP, IL-6 were significantly higher in group B than those in group A (P<0.05). Conclusion: Flurbiprofen axetil could reduce serum hs-CRP, IL-6 levels in patients undergoing Esophageal cancer surgery. (authors)

  9. 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 oral 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.

  10. The Role of Serum Leptin and IL-6 Levels in Post Viral Hepatitis Cirrhotic patients

    International Nuclear Information System (INIS)

    Mohamed, S.K.

    2010-01-01

    Chronic liver disease is characterized by numerous metabolic alterations resulting in the clinical picture of malnutrition or even cachexia and contributing to complications such as hepatic encephalopathy and ascites. Leptin is a hormone that plays an important role in regulating energy intake and expenditure including appetite and metabolism. Interleukin-6 (IL-6), on the other hand, is generally considered to be one of the important cytokines that regulate immunologic and metabolic actions. The aim of the present study was to investigate serum leptin and IL-6 levels in liver cirrhosis, as well as to determine their levels in relation to liver functions and lipid profile. This study was conducted on 25 patients with post- viral hepatic cirrhosis compared to 20 healthy matched individuals served as controls with the same age and sex. The severity of the disease assessed with Child-Pugh criteria yielded 8 patients (3 women, 5 men) with stage A, 10 patients (4 women, 6 men) with stage B and 7 patients (2 women, 5 men) with stage C. Compared to controls, body mass index (BMI) was decreased and reached statistical significance in group C liver cirrhosis (P< 0.05). Also, serum leptin level was highly significantly decreased in the three groups, while IL-6 level showed highly significant increase. Leptin level negatively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin and positively correlated with serum albumin, triglycerides (TG), cholesterol and low density lipoprotein (LDL). In contrast, serum IL-6 level positively correlated with parameters of liver functions and negatively correlated with parameters of lipid profile. Additionally, there was highly significant negative correlation between serum leptin and IL-6 levels (P < 0.001) in post-hepatic cirrhotic patients. We concluded that leptin and IL-6 have important role in diagnosis and prognosis of patients with post-hepatic liver cirrhosis

  11. The Role of Serum Leptin and IL-6 Levels in Post Viral Hepatitis Cirrhotic patients

    Energy Technology Data Exchange (ETDEWEB)

    Mohamed, S.K., E-mail: Safaa-K-mohamed@hotmail.co [Health Radiation Research Department, National Center for Radiation Research and Technology, P. O. Box:29 Nasr City, Cairo (Egypt)

    2010-07-01

    Chronic liver disease is characterized by numerous metabolic alterations resulting in the clinical picture of malnutrition or even cachexia and contributing to complications such as hepatic encephalopathy and ascites. Leptin is a hormone that plays an important role in regulating energy intake and expenditure including appetite and metabolism. Interleukin-6 (IL-6), on the other hand, is generally considered to be one of the important cytokines that regulate immunologic and metabolic actions. The aim of the present study was to investigate serum leptin and IL-6 levels in liver cirrhosis, as well as to determine their levels in relation to liver functions and lipid profile. This study was conducted on 25 patients with post- viral hepatic cirrhosis compared to 20 healthy matched individuals served as controls with the same age and sex. The severity of the disease assessed with Child-Pugh criteria yielded 8 patients (3 women, 5 men) with stage A, 10 patients (4 women, 6 men) with stage B and 7 patients (2 women, 5 men) with stage C. Compared to controls, body mass index (BMI) was decreased and reached statistical significance in group C liver cirrhosis (P< 0.05). Also, serum leptin level was highly significantly decreased in the three groups, while IL-6 level showed highly significant increase. Leptin level negatively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin and positively correlated with serum albumin, triglycerides (TG), cholesterol and low density lipoprotein (LDL). In contrast, serum IL-6 level positively correlated with parameters of liver functions and negatively correlated with parameters of lipid profile. Additionally, there was highly significant negative correlation between serum leptin and IL-6 levels (P < 0.001) in post-hepatic cirrhotic patients. We concluded that leptin and IL-6 have important role in diagnosis and prognosis of patients with post-hepatic liver cirrhosis

  12. Post-MI depression and levels of serum IL-6 and CRP in AMI patients

    International Nuclear Information System (INIS)

    Huang Tiejun

    2004-01-01

    Objective: To explore the relationship between the presence and severity of post-MI depression and the increased inflammatory activity, as marked by the serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) after myocardial infarction. Methods: Serum IL-6 and CRP levels were measured in 58 AMI patients within 36 hours after onset of event. Depression was evaluated by self-reporting standardized questionnaire, using a validated Chinese version of Hospiatla Anxiety and Depression Scale (HADS)-Depression Subscale (7 items) within 7 days. Demographic and medical data including LVEF, NYHA cardiac function grading, atherosclerosis severity shown from angiography as well as cardiac risk factors were recorded. Results: Serum levels of IL-6 and CRP were higher in depressive AMI patients than those in non-depressive ones (0.93 ± 0.64 vs 0.48 ± 0.37 ng/L, P<0.05 and 0.96 ± 0.41 vs 0.47 ± 0.26 mg/dL, P<0.05). Neither levels of IL-6 nor HADS-D scores were found to be correlated to the severity of atherosclerosis shown in angiography. Conclusion: Presence and severity of post-MI depression is associated with increased activity of inflammation in patients after myocardial infarction. (authors)

  13. Correlation between serum interleukin-6 level and type 1 diabetes mellitus: A systematic review and meta-analysis.

    Science.gov (United States)

    Chen, Yin-Ling; Qiao, Yong-Chao; Pan, Yan-Hong; Xu, Yan; Huang, Yong-Cheng; Wang, Yin-Hui; Geng, Li-Jun; Zhao, Hai-Lu; Zhang, Xiao-Xi

    2017-06-01

    This report aimed to explore the association between the change of circulating interleukin-6 (IL-6) in patients and the development of type 1 diabetes mellitus (T1DM). Four databases (PubMed, CNKI, WanFang and Civip) were used to search and list all clinical case-control studies about serum IL-6 level in T1DM patients between Jan 1, 2000 and Aug 31, 2016. A total of 20 case-control studies with 1238 T1DM patients and 742 healthy controls were included in this study. Compared to healthy controls, the serum content of IL-6 in patients with T1DM was significantly greater (overall: SMD, 1.49; 95% CI, 1.04 to 1.93; pAmerican group (SMD, 1.68; 95% CI, 0.85-2.51; pdiabetes mellitus. Copyright © 2017. Published by Elsevier Ltd.

  14. Serum hepcidin levels are associated with serum triglycerides and interleukin-6 concentrations in patients with end-stage renal disease.

    Science.gov (United States)

    Samouilidou, Elisabeth; Pantelias, Konstantinos; Petras, Dimitrios; Tsirpanlis, George; Bakirtzi, Joulia; Chatzivasileiou, George; Tzanatos, Helen; Grapsa, Eirini

    2014-06-01

    Hepcidin has emerged as a peptide with a key role in the regulation of iron homeostasis in patients with chronic kidney disease (CKD), having a strong dependence on inflammation. Recent studies reveal that hepcidin may be also associated with the progression of atherosclerosis. This study was performed to analyze the relation of hepcidin to markers of atherosclerosis and inflammation in patients on dialysis. A total of 90 individuals were enrolled. Sixty patients with end-stage renal disease, who were on hemodialysis (HD) (N = 30) and peritoneal dialysis (N = 30) were compared with 30 normal controls (NC). Age, body mass index, time on dialysis, serum lipids, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured and analyzed in correlation with hepcidin concentration. It was found that patients on HD and peritoneal dialysis have significantly higher (P triglycerides (r = 0.401, P = 0.005), HDL-C (r = -0.268, P = 0.048), CRP (r = 0.436, P = 0.0007) and IL-6 (r = 0.569, P triglycerides (β = 0.402, P = 0.041) and IL-6 (β = 0.559, P = 0.006). Moreover, patients with high triglycerides in combination with high IL-6 levels have significantly increased concentrations of hepcidin than those with low triglycerides and low IL-6 levels (P triglycerides and high IL-6 serum concentrations. This probably suggests that hepcidin may play a role to the progression of atherosclerosis and inflammation, but this hypothesis should be further evaluated. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  15. Application value of Serum Hs-CRP, IL-6 and plasma FIB joint detection in COPD

    Directory of Open Access Journals (Sweden)

    Feng Ji

    2016-11-01

    Full Text Available Objective: To discuss the application value of High sensitivity C-reactive protein (Hs-CRP, interleukin-6 (IL-6 and fibrinogen (FIB joint detection in chronic obstructive pulmonary disease (COPD. Methods: A total of 181 COPD cases were divided to be COPD stable phase group (65 cases and COPD acute exacerbation phase group (116 cases per the course of disease. COPD acute exacerbation phase group was classified into grade I (39 cases, grade II (43 cases and grade III (34 cases based on pulmonary function. Then survival group (87 cases and death group (29 cases were divided based on illness transition. Meanwhile, 80 cases of healthy people at the same phase were set to be healthy group. Differences in levels of Serum hs-CRP, IL-6 and FIB in these groups were analyzed, and according to these indexes, prognostic potency of COPD acute exacerbation phase could be evaluated. Results: Difference in serum hs-CRP, IL-6 and FIB levels in COPD stable phase group, COPD acute exacerbation phase group and healthy group were statistical significant (P<0.05. both for healthy group serum hs-CRP, IL-6 and FIB levels in grade I, II, III of pulmonary function in the COPD acute exacerbation phase group were statistical significant (P<0.05 both for grade 1 < grade 2 < grade 3. Result of person analyzing showed significant positive correlation on grading of pulmonary function and serum hs-CRP, IL-6 and FIB levels, the correlation coefficient was 0.573. Differences of hs-CRP, IL-6 and FIB levels between survival group and death group were statistical significant. Serum hs-CRP, IL-6 and FIB levels were utilized respectively to evaluate area under curve of receiver operating characteristic in prognostic COPD acute exacerbation phase group, namely, 0.836, 0.815, 0.776. Sensitivities of “death”, which was evaluated by the various indexes, respectively showed as: 72.41%, 65.51% and 75

  16. 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

  17. 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.

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

    Science.gov (United States)

    Chen, Qianming; Xia, Juan; Lin, Mei; Zhou, Hongmei; Li, Bingqi

    2007-01-01

    Objective. To examine alteration of serum interleukin-6 and its clinical significance in burning mouth syndrome (BMS) patients. Methods. 48 BMS patients and 31 healthy controls participated in the study. Serum interleukin-6 was measured by means of ELISA. Hamilton rating scale of depression (HRSD) and visual analogue scale (VAS) were used to quantitiate depressive status and pain levels of subjects, respectively. Results. 15 (31%) patients displayed substantial depressive symptoms (HRSD ≧ 16). HRSD scores of patients were significantly higher than controls and positively correlated to their VAS values (P = .002). Serum interleukin-6 in patients was much lower than controls and negatively correlated to their VAS values (P = .011). However, no significant relations were found between interleukin-6 and HRSD scores (P = .317). 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. PMID:17641729

  19. 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.

  20. Serum level of IL-6 in liver cirrhosis patients

    Science.gov (United States)

    Rey, I.; Effendi-YS, R.; Dairi, L. B.; Siregar, G. A.; Zain, L. H.

    2018-03-01

    Cytokines are polypeptides that have a wide spectrum of inflammatory, metabolic, hematopoietic and immunologic regulatory properties. The liver represents an important site of synthesis and clearance organ for several cytokines. This study aimed to evaluate serum IL-6 in liver cirrhosis with the type of underlying disease, child pugh group and various clinical and laboratory parameter. This cross-sectional study was at Adam Malik General Hospital and Pirngadi General Hospital from July - December 2016. We examine 75 patients with liver cirrhosis. The exclusion criteria were hepatoma, sepsis and renal impairment. There were 28 (37.3%), 8 (10.6%) and 39 (52%) for HBV-positive; HCV-positive and HBV- HCV negative liver cirrhosis patients, respectively were 14 (18.7 %), 15 (20 %) and 46 (61.3%) for Child- Pugh A, B and C respectively. There was no significant difference value of IL-6 between HBV positive, HCV positive, and HBV-HCV negative group (7.7/6.1/10.9). There was no significant difference value of IL-6 between child pugh A, B, and C group (4.2/11.0/7.9).

  1. 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...

  2. 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.

  3. The Role of Serum High Mobility Group Box 1 and Interleukin-6 Levels in Acute Pancreatitis: A Meta-Analysis.

    Science.gov (United States)

    Li, Nuo; Wang, Bao-Ming; Cai, Shuang; Liu, Peng-Liang

    2018-01-01

    The purpose of this meta-analysis was to comprehensively investigate the correlation between high mobility group box 1 (HMGB1) and interleukin-6 (IL-6) in relation to acute pancreatitis. A highly regulated exploration of various electronic databases, supplemented by manual searching methods, was performed in an attempt to identify pertinent articles of a useful nature. Subsequently, high-quality cohort studies that were deemed to comply with the arduous inclusion and exclusion criteria were selected for our meta-analysis. The extensive data analyses reported in our meta-analysis were conducted in connection with the Comprehensive Meta-analysis 2.0 (CMA 2.0). A total of 395 studies (135 Chinese studies and 260 English studies) were initially retrieved. 27 of those studies were selected for our meta-analysis, comprising of 896 cases of mild acute pancreatitis (MAP), 700 cases of severe acute pancreatitis (SAP) as well as 312 healthy controls. Pooled data suggested that serum HMGB1 and IL-6 levels of SAP and MAP patients were higher than in healthy controls. Moreover, serum HMGB1 and IL-6 levels of SAP patients exhibited significantly higher levels than in that of MAP patients. Based on the rigorous investigation of our meta-analysis, it was concluded that serum HMGB1 and IL-6 levels might be used as effective indicators for pancreatic lesions as well as the degree of inflammatory response, owing ultimately to the observations and data analyses, suggesting that serum HMGB1 and IL-6 levels share a close correlation with the severity of pancreatitis. J. Cell. Biochem. 119: 616-624, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Treatment with anti-IL-6 receptor antibody prevented increase in serum hepcidin levels and improved anemia in mice inoculated with IL-6–producing lung carcinoma cells

    International Nuclear Information System (INIS)

    Noguchi-Sasaki, Mariko; Sasaki, Yusuke; Shimonaka, Yasushi; Mori, Kazushige; Fujimoto-Ouchi, Kaori

    2016-01-01

    Hepcidin, a key regulator of iron metabolism, is produced mainly by interleukin-6 (IL-6) during inflammation. A mechanism linking cancer-related anemia and IL-6 through hepcidin production is suggested. To clarify the hypothesis that overproduction of IL-6 elevates hepcidin levels and contributes to the development of cancer-related anemia, we evaluated anti-IL-6 receptor antibody treatment of cancer-related anemia in an IL-6–producing human lung cancer xenograft model. Nude mice were subcutaneously inoculated with cells of the IL-6–producing human lung cancer cell line LC-06-JCK and assessed as a model of cancer-related anemia. Mice bearing LC-06-JCK were administered rat anti-mouse IL-6 receptor antibody MR16-1 and their serum hepcidin levels and hematological parameters were determined. LC-06-JCK–bearing mice developed anemia according to the production of human IL-6 from xenografts, with decreased values of hemoglobin, hematocrit, and mean corpuscular volume (MCV) compared to non–tumor-bearing (NTB) mice. LC-06-JCK–bearing mice showed decreased body weight and serum albumin with increased serum amyloid A. MR16-1 treatment showed significant inhibition of decreased body weight and serum albumin levels, and suppressed serum amyloid A level. There was no difference in tumor volume between MR16-1-treated mice and immunoglobulin G (IgG)-treated control mice. Decreased hemoglobin, hematocrit, and MCV in LC-06-JCK–bearing mice was significantly relieved by MR16-1 treatment. LC-06-JCK–bearing mice showed high red blood cell counts and erythropoietin levels as compared to NTB mice, whereas MR16-1 treatment did not affect their levels. Serum hepcidin and ferritin levels were statistically elevated in mice bearing LC-06-JCK. LC-06-JCK–bearing mice showed lower values of MCV, mean corpuscular hemoglobin (MCH), and serum iron as compared to NTB mice. Administration of MR16-1 to mice bearing LC-06-JCK significantly suppressed levels of both serum hepcidin and

  5. 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.

  6. 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.

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

    Science.gov (United States)

    Randau, Thomas M; Friedrich, Max J; Wimmer, Matthias D; Reichert, Ben; Kuberra, Dominik; Stoffel-Wagner, Birgit; Limmer, Andreas; Wirtz, Dieter C; Gravius, Sascha

    2014-01-01

    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.

  8. 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.

  9. 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

    2018-05-01

    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.

  10. Clinical significance of measurements of serum IL-6 levels in patients with cardiovascular and cerebrovascular diseases

    International Nuclear Information System (INIS)

    Wu Cuihua; Luo Nanping; Zhang Daojie; Wei Hong

    2004-01-01

    Objective: To explore the clinical significance of changes of serum IL-6 levels in patients with cardiovascular and cerebrovascular diseases. Methods: Serum IL-6 levels were determined with RIA in 35 patients with coronary heart disease, 20 patients with essential hypertension, 28 patients with cerebral infarction and 30 controls. Results: Serum IL-6 levels in patients with coronary heart disease and cerebral infarction were significantly higher than those in the controls (P 0.05). Conclusion: Serum IL-6 levels changes could reflect the severity of the inflammatory process and would be helpful in clinical assessment. (authors)

  11. Changes in serum interleukin-6, C-reactive protein and thrombomodulin levels under periodontal ultrasonic debridement.

    Science.gov (United States)

    Ushida, Yuka; Koshy, Geena; Kawashima, Yoko; Kiji, Makoto; Umeda, Makoto; Nitta, Hiroshi; Nagasawa, Toshiyuki; Ishikawa, Isao; Izumi, Yuichi

    2008-11-01

    This study aimed to compare the effect of single-visit full-mouth mechanical debridement (FMD) and quadrant-wise mechanical debridement (QMD) on the levels of serum interleukin (IL)-6, C-reactive protein (CRP) and soluble thrombomodulin. Thirty-six subjects with chronic periodontitis were randomly allocated to three groups: undergoing QMD, single-visit FMD with povidone iodine or with water. Serum IL-6 and soluble thrombomodulin were measured by enzyme-linked immunosorbent assay, and serum CRP was measured by the latex-enhanced nephelometric method. Serum IL-6 level increased significantly immediately after debridement in all the three groups, with this increase being greatest in the full-mouth groups. However, the increase in the full-mouth groups was not significantly higher than that of quadrant-wise group. In the quadrant-wise group, serum IL-6 level decreased significantly 1 month after debridement compared with baseline. Serum-soluble thrombomodulin decreased significantly in the full-mouth groups but not in the quadrant-wise group. Changes in CRP level were not significant at baseline or after debridement in all the three groups. FMD increased serum IL-6 and reduced serum-soluble thrombomodulin to a greater extent than QMD, suggesting that the former technique has stronger transient effects on systemic vascular endothelial functions than the latter.

  12. The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein.

    Science.gov (United States)

    Shimada, Yasuko; Komatsu, Yasutaka; Ikezawa-Suzuki, Ikuyo; Tai, Hideaki; Sugita, Noriko; Yoshie, Hiromasa

    2010-08-01

    Previous studies suggest that periodontitis is closely related to obesity and metabolic syndrome. Leptin, a pleiotrophic hormone produced by adipose tissue, has been reported to be related to periodontitis. This study investigates the effects of periodontal treatment on the serum levels of leptin and other cytokines in patients with chronic periodontitis (CP). Serum samples were taken from 33 CP patients (22 non-smokers, 11 smokers) and 18 healthy subjects. The serum leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, and C-reactive protein (CRP) levels were measured before and after non-surgical periodontal treatment. Significant differences between healthy and CP patients were found in serum leptin, IL-6, and CRP levels (P = 0.0018, P = 0.0064, and P = 0.0095, respectively). The serum leptin level was associated with mean probing depth, mean clinical attachment level, mean alveolar bone loss, and body mass index. There were significant associations between serum leptin levels and IL-6 and CRP levels. After non-surgical periodontal treatment, serum leptin, IL-6, and CRP levels were significantly decreased (mean +/- SD before and after, P value, respectively: leptin, 8.02 +/- 5.5, 7.10 +/- 4.4, P = 0.015; IL-6, 1.73 +/- 1.02, 1.36 +/- 0.73, P = 0.048; and CRP, 802.0 +/- 1065, 491.2 +/- 479.3, P = 0.047). Periodontal treatment is effective in reducing serum leptin, IL-6, and CRP levels. The results suggest that leptin, IL-6, and CRP could be mediating factors that connect metabolic syndrome and periodontitis.

  13. 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

  14. 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.

  15. 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

  16. Association of interleukin 2 (IL-2), interleukin 6 (IL-6), and TNF-alpha (TNFα) gene polymorphisms with paranoid schizophrenia in a Polish population.

    Science.gov (United States)

    Paul-Samojedny, Monika; Owczarek, Aleksander; Kowalczyk, Małgorzata; Suchanek, Renata; Palacz, Marta; Kucia, Krzysztof; Fila-Daniłow, Anna; Borkowska, Paulina; Kowalski, Jan

    2013-01-01

    Numerous reports have brought attention to the potential role of cytokines in schizophrenia. The aim of the study was to determine whether polymorphisms of IL-2, IL-6, and TNFα genes are risk factors for development of paranoid schizophrenia in a Polish population. Promoter polymorphisms of IL-6 (rs1800795), TNFα (rs1800629), and IL-2 (rs2069762) genes in patients (N=115) and controls (N=135) were genotyped by PCR-RFLP and AS-PCR methods, respectively. Genotype TT and allele T for IL-2 polymorphism, and genotype AA and allele A for TNFα polymorphism were found to be significantly associated with paranoid schizophrenia. Similarly, haplotypes CTA and GTA increased the risk (4.4 times and 5.9 times, respectively) of schizophrenia. To reveal associations between Positive and Negative Symptom Scale subscales and age at onset of schizophrenia, the authors used a novel method called Grade Correspondence Analysis. This analysis revealed that patients with early age at onset have higher scores on the Negative and General subscales of PANSS, and, in that group of patients, haplotype CTA was the most represented. As far as is known, this analysis was used for the first time with reference to genetic data.

  17. 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)

  18. Changes of serum procalcitonin (PCT) and IL-6 levels in patients with sepsis

    International Nuclear Information System (INIS)

    Wang Jinjiang

    2007-01-01

    Objective: To investigate the importance of determination of changes of serum procalcitonin (PCT) and IL-6 levels in patients with sepsis. Methods: Serum PCT (with double-sandwich immunofluorescence assay) and IL-6 (with ELISA) levels were measured repeatedly in 130 patients with sepsis on d1, d3, d5, d7 after admission. Values in 130 healthy individuals were also measured as control. Results: The serum levels of PCT and IL-6 in the patients with sepsis of admission were significantly higher than those in controls. The levels dropped markedly in the survivors by d7. Among the septic patients, the levels in the succumbed patients were significantly higher those in the survivors (P<0.05). Conclusion: Serum PCT and IL-6 values appeared to be of prognostic value in patients with sepsis. (authors)

  19. Serum TNF-α, IL-6 and Resistin Levels in Chronic Plaque Psoriasis

    Directory of Open Access Journals (Sweden)

    Yasemin Yıldırım

    2012-09-01

    Full Text Available Background and Design: Psoriasis is a chronic recurrent inflammatory disease of the skin. Despite previous extensive studies, etiology is still unclear. Obesity is a significant risk factor for psoriasis and body mass index (BMI correlates with the disease severity. In recent years, the relationship between psoriasis and adipose tissue cytokines has been reported. Therefore, in this study, we aimed to determine the levels of adipose tissue cytokines TNF-α, IL-6 and resistin in psoriasis patients and to evaluate their relation with disease severity.Material and Methods: Our study was performed between January 2010 and February 2010 on a total of 40 patients who were admitted to Abant Izzet Baysal University, Medical School Clinic of Dermatology with complaints of psoriasis. Additionally, forty healthy individuals whose age, gender and BMI did not differ from the patients’ ones formed the control group. TNF-α, IL-6, and resistin levels were measured in both the patients diagnosed with psoriasis and the control group using ELISA methods. The t-test and Mann-Whitney U test were performed to examine the differences between the two groups. Results: In our study, TNF-α, IL-6, and resistin levels were all significantly elevated in the patient group, and serum IL-6 and resistin correlated with disease severity. Psoriasis Area Severity Index (PASI score showed statistically significant association with IL-6 and resistin levels. Furthermore, it was detected that BMI did not correlate with serum TNF-α, IL-6, and resistin levels.Conclusion: The results of our study showed that TNF-α, IL-6, and resistin play a part in psoriasis etiopathogenesis, and IL-6 and resistin can be used as markers to assess the severity of the disease. Also, our study showed that the elevation in serum TNF-α, IL-6, and resistin levels is independent from the increase in adipose tissue. Larger studies are needed to support our findings.

  20. Three-Dimensional Conformal Radiotherapy in Prostate Cancer Patients: Rise in Interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, Tumor Necrosis Factor-{alpha}, MIP-1-{alpha}, and LIF Levels

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Lopes, Carlos [Universidade do Vale do Paraiba, Centro de Oncologia Radioterapica do Vale do Paraiba, Universidade do Vale do Paraiba Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, Sao Jose dos Campos, Sao Paulo (Brazil); Callera, Fernando, E-mail: fcallera@gmail.com [Centro de Hematologia Onco-hematologia e Transplantes de Medula Ossea do Vale do Paraiba, Sao Paulo (Brazil)

    2012-03-15

    Purpose: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-{alpha}), macrophage inflammatory protein-1-alpha (MIP-1-{alpha}) and leukemia inhibitory factor (LIF) in patients with prostate cancer. Methods and Materials: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. Results: The mean IL-2 values were elevated before and during the RT in contrast with those of IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. Conclusions: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.

  1. 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 maca consumers when compared to non-consumers (P maca consumers successfully completed the SUCSD test compared to non-consumers (P 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.

  2. Clinical significance of changes of serum IL-6 and TNF-α levels in rat models of hypoxic-ischemia brain injury

    International Nuclear Information System (INIS)

    Niu Tingxian; Shi Zhiyong; Luo Jianjun

    2009-01-01

    Objective: To explore the clinical significance of changes of serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in rat models of hypoxic-ischemia (HI) brain injury. Methods: Seventy five rat HI brain injury nodels were prepared with bilateral occlusion of common carotid artery for 24rs followed 2hrs later by hypoxia (breathing 8% oxygen) for 2hrs. One fifth of the animals were sacrificed at 4h, 8h, 12h, 24h and 48h later respectively, the serum and brain homogenate concentrations of IL-6 and TNF-α were determined with RIA and brain tissues were pathologically examined. Results: The concentrations of IL-6 and TNF-α were dynamically changed within 48h in serum and brain homogenate. Peak values occurred at 24h with serum and at 12h with brain homogenate. Meanwhile, levels of both cytokines were significantly higher in the models than those in controls (P<0.01 or P<0.05). Conclusion: The concentrations of IL-6 and TNF-α were dynamically(sham operation only, 15 animals) changed and might be regarded as the clinical markers of degree of HI brain injury. (authors)

  3. Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19-9) in gastric cancer.

    Science.gov (United States)

    Lukaszewicz-Zając, Marta; Mroczko, Barbara; Gryko, Mariusz; Kędra, Bogusław; Szmitkowski, Maciej

    2011-06-01

    Gastric cancer (GC) is a second most common cause of cancer-related death and represents an inflammation-driven malignancy. It has been suggested that interleukin 6 (IL-6) and C-reactive protein (CRP) play a potential role in the growth and progression of GC. The aim of the present study was to compare clinical significance of IL-6 and CRP with classic tumor markers-carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in GC patients. The study included 92 patients with GC and 70 healthy subjects. The serum concentrations of IL-6, CEA and CA 19-9 were determined using immunoenzyme assays, whereas CRP using immunoturbidimetric method. We defined the diagnostic criteria and prognostic value for proteins tested. In GC patients, the serum concentrations of all the proteins tested were significantly higher than in healthy subjects. The IL-6, CEA and CA 19-9 levels correlated with nodal metastases, while CRP with tumor stage, gastric wall invasion, presence of nodal and distant metastases. Diagnostic sensitivity of IL-6 was higher (85%) than those of other markers (CRP 66%, CA 19-9 34%, CEA 22%) and increased in combined use with CRP or CEA (88%). The area under ROC curve for IL-6 was larger than those of CRP and classic tumor markers (CEA and CA 19-9). None of the proteins tested was independent prognostic factor for the survival of GC patients. Our findings indicate better usefulness of serum proinflammatory proteins-IL-6 and CRP than classic tumor markers-CEA and CA 19-9 in the diagnosis of GC.

  4. 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......, but S-YKL-40 show a strong positive correlation with S-IL-6 consistent with a possible IL-6 mediated regulation of YKL-40 secretion demonstrated in previous studies. Table 1     Normal S-YKL-40 N   Median (range)     Elevated S-YKL-40 N   Median (range)     p-value   S-IL-6, ng/L             PB 23 3 (1...

  5. The Dose–Response Association between Nitrogen Dioxide Exposure and Serum Interleukin-6 Concentrations

    Directory of Open Access Journals (Sweden)

    Jennifer L. Perret

    2017-05-01

    Full Text Available Systemic inflammation is an integral part of chronic obstructive pulmonary disease (COPD, and air pollution is associated with cardiorespiratory mortality, yet the interrelationships are not fully defined. We examined associations between nitrogen dioxide (NO2 exposure (as a marker of traffic-related air pollution and pro-inflammatory cytokines, and investigated effect modification and mediation by post-bronchodilator airflow obstruction (post-BD-AO and cardiovascular risk. Data from middle-aged participants in the Tasmanian Longitudinal Health Study (TAHS, n = 1389 were analyzed by multivariable logistic regression, using serum interleukin (IL-6, IL-8 and tumor necrosis factor-α (TNF-α as the outcome. Mean annual NO2 exposure was estimated at residential addresses using a validated satellite-based land-use regression model. Post-BD-AO was defined by post-BD forced expiratory ratio (FEV1/FVC < lower limit of normal, and cardiovascular risk by a history of either cerebrovascular or ischaemic heart disease. We found a positive association with increasing serum IL-6 concentration (geometric mean 1.20 (95% CI: 1.1 to 1.3, p = 0.001 per quartile increase in NO2. This was predominantly a direct relationship, with little evidence for either effect modification or mediation via post-BD-AO, or for the small subgroup who reported cardiovascular events. However, there was some evidence consistent with serum IL-6 being on the causal pathway between NO2 and cardiovascular risk. These findings raise the possibility that the interplay between air pollution and systemic inflammation may differ between post-BD airflow obstruction and cardiovascular diseases.

  6. Serum IL 6 and umbilical artery Doppler indices in pre-eclamptic ...

    African Journals Online (AJOL)

    Medhat Y. Anwer

    2016-03-07

    Mar 7, 2016 ... increased activation of the complement system.6 Macrophages, neutrophils ..... teine, folic acid and vitamin B 12 levels with the severity of pre- · eclampsia and ... Maternal serum levels of TNF-alpha and IL-6 long after delivery.

  7. Clinical significance of changes of plasma endothelin vasoactive factors (ET and NO) as well as serum related interleukin (IL-6 and IL-8) levels in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Chen Ying

    2009-01-01

    Objective: To investigate the clinical etiological significance of changes of plasma endothelin (ET) and nitric oxide (NO) as well as serum interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in patients with pregnancy induced hypertension. Methods: Plasma ET (with RIA), NO (with biochemistry) and serum IL-6, IL-8 (with RIA) levels were measured in 32 pregnant women with PIH, 35 normal pregnant women without PIH and 35 non-pregnant women (as controls). Results: The plasma ET, NO level were significantly higher in normal pregnant women than those in the non-pregnant women controls, while serum levels of IL-6 and IL-8 levels were only slightly higher without significance (P>0.05). Before treatment, the blood ET, IL-6 and IL- 8 levels were significantly higher in patients with pregnancy induced hypertension than those in the control (P<0.01), while plasma levels of NO were significantly decreased (P<0.01), Two weeks after treatment, the plasma ET, NO and serum IL-6 and IL-8 levels were markedly corrected with no significantly differences from those in controls. The ET levels and serum IL-6, IL-8 levels were mutually positively correlated (r=0.6097, 0.7213, P<0.01). Conclusion: Determination of changes of plasma ET and NO, serum IL-6 and IL-8 levels in patients with pregnancy induced hypertension was helpful for outcome prediction. (authors)

  8. Elevated serum high-sensitivity C-reactive protein levels in fibromyalgia syndrome patients correlate with body mass index, interleukin-6, interleukin-8, erythrocyte sedimentation rate.

    Science.gov (United States)

    Xiao, Yangming; Haynes, Wanda L; Michalek, Joel E; Russell, I Jon

    2013-05-01

    The levels of several inflammatory cytokines are abnormal in many patients with the fibromyalgia syndrome (FMS) and may play a role in its pathogenesis. The inflammatory marker C-reactive protein (CRP) is associated with the disease activity in patients with inflammatory rheumatic diseases, but its role in FMS is unknown. We undertook this study to determine whether high-sensitivity CRP (hsCRP) is elevated in FMS and whether its levels relate to key biologic or clinical measures. One hundred and five patients with FMS (1990 ACR criteria) and 61 healthy normal controls (HNC) at a ratio of 2:1 were recruited. The serum concentrations of hsCRP, interleukin-8 (IL-8), and interleukin-6 (IL-6) were assessed using enzyme-linked immunosorbent assays. The hsCRP levels were marginally higher in FMS than in HNC (p = 0.06) and its abnormality rate (>1.5 SD above the HNC mean) was significantly higher in FMS (25 %) compared with HNC (6.8 %) (p = 0.03). Serum IL-8 levels, IL-6 levels, and erythrocyte sedimentation rate (ESR) in FMS did not differ from those in HNC. Body mass index (BMI), ESR, IL-8, and IL-6 levels correlated with hsCRP levels in FMS. No associations were found between hsCRP and age, gender, ethnicity, or other clinical measures. Serum CRP levels were higher in FMS and significantly correlated with BMI, ESR, IL-8, and IL-6 levels, suggesting that inflammation may contribute to the symptoms in some FMS patients, particularly those who are obese. Weight loss and therapies directed against inflammation may be useful in the management of FMS patients with elevated hsCRP.

  9. Clinical significance of changes of serum TNF-α and IL-6 levels in elderly patients with chronic bronchial asthma

    International Nuclear Information System (INIS)

    Li Mei

    2005-01-01

    Objective: To explore the clinical significance of changes of serum TNF-α and IL-6 levels in elderly patients with chronic bronchial asthma. Methods: Serum TNF-α and IL-6 levels were determined with RIA in 55 elderly patients with chronic bronchial asthma and 35 controls. Results: Serum TNF-α and IL-6 levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Abnormal high serum TNF-α and IL-6 levels were important pathophysiologic features in chronic bronchial asthma. (authors)

  10. 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)

  11. Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Ward Norman H

    2010-03-01

    Full Text Available Abstract Background Increased intracranial pressure (ICP is a serious, life-threatening, secondary event following traumatic brain injury (TBI. In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patient's risk for developing this pathology. Methods In the present study, we employed antibody array and Luminex-based screening methods to interrogate the levels of inflammatory cytokines in the serum of healthy volunteers and in severe TBI patients (GCS≤8 with or without incidence of elevated intracranial pressure (ICP. De-identified samples and ELISAs were used to confirm the sensitivity and specificity of IL-6 as a prognostic marker of elevated ICP in both isolated TBI patients, and polytrauma patients with TBI. Results Consistent with previous reports, we observed sustained increases in IL-6 levels in TBI patients irrespective of their ICP status. However, the group of patients who subsequently experienced ICP ≥ 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained ≤20 mm Hg. When blinded samples (n = 22 were assessed, a serum IL-6 cut-off of 128 pg/ml correctly identified 85% of isolated TBI patients who subsequently developed elevated ICP, and values between these cut-off values correctly identified 75% of all patients whose ICP remained ≤20 mm Hg throughout the study period. In contrast, the marker had no prognostic value in predicting elevated ICP in polytrauma patients with TBI. When the levels of serum IL-6 were assessed in patients with orthopedic injury (n = 7 in the absence of TBI, a significant increase was found in these patients compared to healthy volunteers, albeit lower than that observed in TBI patients. Conclusions Our results suggest that serum IL-6 can be used for the

  12. Serum concentration of IL-6, IL-2, TNF-α, and IFNγ in Vitiligo patients

    Directory of Open Access Journals (Sweden)

    Suman Singh

    2012-01-01

    Full Text Available Background: Vitiligo is an acquired depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. Although the etiology of vitiligo is unknown, over the last few years, substantial data from clinical research has greatly supported the ′Autoimmune theory′ and this is supported by the frequent association of vitiligo with disorders that have an autoimmune origin, including Hashimoto′s thyroiditis, Graves disease, type 1 insulin-dependent diabetes mellitus, and Addison′s disease. As cytokines are important mediators of immunity, there is evidence to suggest that they play a major role in the pathogenesis of autoimmune diseases. Aim: Keeping this in view we have assayed sera for cytokine IL-6, IL-2, Tumor necrosis factor (TNF-α, and IFNγ in 80 cases of vitiligo and compared it with healthy subjects, in order to find out whether they play a role in the pathogenesis of vitiligo or not. Materials and Methods: Serum IL-6, IL-2, TNF-α, and IFNγ were done by the indirect enzyme linked immunosorbent assay (ELISA. Results: The mean serum IL-6 and IL-2 levels in the patient group were significantly higher when compared with those of the normal controls. The mean serum IFNγ level in patients with vitiligo was significantly lower than that in the control group. There was no significant difference in the serum level of TNF-α between vitiligo and healthy controls. Conclusion : An increase in the production of proinflammatory cytokines such as IL-6 and IL-2 in vitiligo patients may play an important role in melanocytic cytotoxicity. Thus, we speculate that the cytokine production of epidermal microenvironment may be involved in vitiligo.

  13. Clinical significance of changes of serum NSE, TNF-α and IL-6 levels in patients with hypoxic ischemic encephalopathy

    International Nuclear Information System (INIS)

    Zhang Yuhong; Zhang Yujuan; Zhou Xiujuan; Shan Huali

    2010-01-01

    Objective: To study the clinical significance of changes of serum NSE, TNF-α and IL-6 levels in neonates with hypoxic ischemic encephalopathy. Methods: Serum NSE (with ELISA) and TNF-α, IL-6 (with RIA) levels were measured in 30 neonates with hypoxic ischemic encephalopathy and 30 controls. Results: Serum NSE, TNF-α and IL-6 levels were significantly higher in neonates with hypoxic-ischemic encephalopathy than those in controls (P<0.01). Serum NSE levels were positively correlated with those of TNF-α, IL-6 (r=0.5812, 0.6014, P<0.01). Conclusion: Serum NSE, TNF-α and IL-6 levels were closely related to the diseases process of hypoxic-ischemic encephalopathy. (authors)

  14. Study on the changes of serum IL-2, IL-6, IL-8 and TNF levels in patients with diabetic nephrosis

    International Nuclear Information System (INIS)

    Qin Wenjing

    2005-01-01

    Objective: To investigate the changes of serum IL-2, IL-6, IL-8 and TNF levels in patients with diabetic nephrosis. Methods: Serum IL-2, IL-6, IL-8 and TNF levels were measured with RIA in 38 patients with diabetic nephrosis and 36 controls. Results: Serum levels of IL-6, IL-8 and TNF were significantly higher in patients with diabetic nephrosis than those in controls (P<0.01), but serum IL-2 levels were significantly lower in the patients (P<0.01). Conclusion: These cytokines participated in the pathogenesis of diabetic nephrosis. Monitoring the changes of their serum levels was helpful for the management of the disease. (authors)

  15. Study on the changes of serum IL-2, IL-6 and TNF-α levels in patients with psoriasis

    International Nuclear Information System (INIS)

    Xie Chuntao

    2007-01-01

    Objective: To investigate the changes of serum IL-2, IL-6 and TNF-α levels in patients with psoriasis. Methods: Serum IL-2, IL-6 and TNF-α levels were measured with KIA in 38 patients with psoriasis and 35 controls. Results: Serum levels of IL-6 and TNF-α were significantly higher in patients with psoriasis than those in controls (P<0.01), but serum IL-2 levels were significantly lower (P<0.01). Conclusion: These cytokines participated in the pathogenesis of psoriasis. Monitoring the changes of their serum levels was helpful for the management of the diseases. (authors)

  16. Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis

    Science.gov (United States)

    Migita, K; Izumi, Y; Jiuchi, Y; Kozuru, H; Kawahara, C; Izumi, M; Sakai, T; Nakamura, M; Motokawa, S; Nakamura, T; Kawakami, A

    2014-01-01

    The Janus kinase inhibitor tofacitinib is currently being investigated as a disease-modifying agent in rheumatoid arthritis (RA). We investigated the in-vivo effects of tofacitinib treatment for 4 weeks on elevated circulating acute-phase serum amyloid (SAA) levels in 14 Japanese patients with RA. SAA levels fell from 110·5 ± 118·5 μg/ml (mean ± standard deviation) at treatment initiation to 15·3 ± 13·3 μg/ml after 4 weeks treatment with tofacitinib. The reduction in SAA levels was greater in patients receiving tofacitinib plus methotrexate compared with those receiving tofacitinib monotherapy. Tofacitinib was also associated with reduced serum interleukin (IL)-6, but had no effect on serum levels of soluble IL-6 receptor. Patients were divided into groups with adequate (normalization) and inadequate SAA responses (without normalization). Serum IL-6 levels were reduced more in the group with adequate SAA response compared with those with inadequate SAA response. These results suggest that tofacitinib down-regulates the proinflammatory cytokine, IL-6, accompanied by reduced serum SAA levels in patients with active RA. The ability to regulate elevated serum IL-6 and SAA levels may explain the anti-inflammatory activity of tofacitinib. PMID:24665995

  17. 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

  18. Relationship of obesity with serum concentrations of leptin, CRP and IL-6 in breast cancer survivors

    International Nuclear Information System (INIS)

    Babaei, Z; Mosapour, A.; Moslemi, D.; Parsian, H.; Pouramir, M.; Khafri, S.

    2015-01-01

    Introduction: Several mechanisms have been proposed to explain the adverse effect of obesity on quality of life among women with breast cancer, including alteration in some inflammatory markers. The aim of this study was to determine the status of serum levels of leptin, IL-6 and CRP in obese, overweight and normal weight breast cancer survivors in order to determine the relationship between inflammatory markers’ levels and obesity. Materials and methods: This cross-sectional study was done on 75 women with breast cancer, 30 obese, 15 overweight and 30 normal weight patients. Serum leptin, IL-6, CRP, total protein, albumin and lipid profile as well as anthropometric parameters were measured in three groups. Results: Serum leptin levels of obese patients were significantly higher than those of overweight and normal weight patients ( P < 0.05). Higher serum CRP and lower albumin levels were observed in obese patients in comparison with normal weight patients ( P < 0.05). HDL-C level was significantly different between overweight and normal weight patients ( P < 0.05). Significant differences in serum IL-6 levels were not observed between the study groups ( P > 0.05). Moreover, multiple regression analysis showed that leptin was significantly associated with BMI ( P < 0.001), while albumin was negatively correlated with BMI ( P < 0.05). CRP levels were significantly correlated with BMI and waist-to-hip ratio (WHR) ( P < 0.05). Conclusions: In conclusion, high leptin levels and alteration in acute phase proteins in obese patients may exaggerate the inflammation status. As inflammation has the potential to increase the susceptibility of the patients to metastasis development, it is necessary to decline its rate.

  19. The efficacy of radiofrequency ablation in the treatment of pediatric arrhythmia and its effects on serum IL-6 and hs-CRP.

    Science.gov (United States)

    Li, Chunli; Jia, Libo; Wang, Zhenzhou; Niu, Ling; An, Xinjiang

    2017-10-01

    The aim of this study was to investigate the efficacy of radiofrequency ablation in the treatment of pediatric arrhythmia and to assess the changes in serum interleukin-6 (IL-6) and hs-CRP levels after treatment. Hundred and six children with tachyarrhythmia who were admitted to Xuzhou Children's Hospital from November, 2014 to December, 2015 were recruited for study. The efficacies of radiofrequency in the treatment of different types of arrhythmia were analyzed. Successful ablation was found in 104 cases (98.11%) and recurrence was found in 7 cases (6.73%). Among 62 cases of atrioventricular reentrant tachycardia (AVRT), successful ablation was found in 60 cases (96.77%) and recurrence was found in 3 cases (4.84%). Among 33 cases of atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation was found in 33 cases (100%) and recurrence was found in 2 cases (6.06%). Among 5 cases of ventricular tachycardia (VT), successful ablation was found in 5 cases (100%) and no recurrence was found. Among 4 cases of atrial tachycardia (AT), successful ablation was found in 4 cases (100%) and recurrence was found in 1 case (25%). Among 2 cases of atrial flutter (AFL), successful ablation was found in both (100%) and recurrence was found in 1 case (50%). After operation, the levels of IL-6 and hs-CRP were increased and were continually increased within 6 h after operation. The levels of IL-6 and hs-CRP at 24 h after operation were reduced but still higher than preoperative levels. The duration of radiofrequency and ablation energy were positively correlated with the levels of IL-6 and hs-CRP, while the number of discharges was not significantly correlated with either. In conclusion, radiofrequency ablation is a safe and effective treatment for pediatric arrhythmia. Postoperative monitoring of IL-6 and hs-CRP levels is conducive to understanding postoperative myocardial injury and inflammatory response.

  20. Effects of metformin treatment on serum levels of C-reactive protein and interleukin-6 in women with polycystic ovary syndrome: a meta-analysis

    Science.gov (United States)

    Wang, Jiao; Zhu, Lingyan; Hu, Kaixiang; Tang, Yunliang; Zeng, Xiangxia; Liu, Jianying; Xu, Jixiong

    2017-01-01

    Abstract Background: Metformin is effective for the treatment of polycystic ovary syndrome (PCOS), but conflicting results regarding its impact on serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in women with PCOS have been reported. To provide high-quality evidence about the effect of treatment with metformin on CRP and IL-6 in PCOS, relevant studies that assessed the serum levels of CRP and IL-6 in women with PCOS receiving metformin treatment were reviewed and analyzed. Methods: A literature search was conducted in the Science Citation Index, PubMed, Embase, and Cochrane Library databases, and personal contact was made with the authors. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (95% CIs). To ensure synthesis of the best available evidence, subgroup analysis, sensitivity analysis, meta-regression analysis, and publication bias were performed. Results: Of 216 studies identified, 20 were included in the meta-analysis (7 prospective, nonrandomized studies, and 13 randomized control trials). Data suggest that serum levels of CRP were decreased after metformin treatment in PCOS patients with an SMD (95% CI) of −0.86 [−1.24 to −0.48] and P = .000 (random-effects). However, significant heterogeneity was detected across studies (I2 = 84.6% and P = .000). Unfortunately, the sources of heterogeneity were not found by subgroup analysis and meta-regression analysis. Serum IL-6 concentrations were not significantly changed after metformin treatment in PCOS with an SMD (95% CI) of −0.48 [−1.26 to 0.31] and P > .05 (random-effects). Significant heterogeneity was also detected across studies (I2 = 90.9% and P = .000). The subgroup analysis suggested that treatment-related reductions in serum IL-6 levels were significantly correlated with BMI, whereas the sources of heterogeneity were not found. In addition, we noticed that metformin treatment could decrease

  1. Cutaneous expressions of interleukin-6 and neutrophil elastase as well as levels of serum IgA antibodies to gliadin nonapeptides, tissue transglutaminase and epidermal transglutaminase: implications for both autoimmunity and autoinflammation involvement in dermatitis herpetiformis.

    Science.gov (United States)

    Gornowicz-Porowska, Justyna; Bowszyc-Dmochowska, Monika; Seraszek-Jaros, Agnieszka; Kaczmarek, Elżbieta; Pietkiewicz, Paweł; Dmochowski, Marian

    2014-01-01

    Dermatitis herpetiformis (DH) seems to be a chronic immune-mediated inflammatory disease of partially known origin. In light of its known biological functions and its involvement in tissue pathology in other disease states, particularly in nickel-induced allergic contact dermatitis coexisting with DH, it would appear that the central and peripheral response by neutrophils and their mediators (e.g. neutrophil elastase - NE) in DH may be partially mediated by interleukin-6 (IL-6). The aim of the study was to assess the role of IL -6 in DH lesions by examining the relationships between IL -6/NE cutaneous expression and levels of serum anti-nonapeptides of gliadin (npG) IgA, anti-tissue transglutaminase (tTG) immunoglobulin A (IgA), anti-epidermal transglutaminase (eTG) IgA in DH. In total, 24 DH patients having IgA cutaneous deposition were studied. Immunohistochemistry on paraffin-embedded sections with quantitative digital morphometry was used to measure the intensity of IL -6 and NE cutaneous expressions. Levels of serum anti-npG IgA, anti-tTG IgA and anti-eTG IgA were evaluated with ELISA. We found no statistically significant correlation between the NE and IL -6 expression intensities. Our results revealed also a lack of correlations between NE/IL -6 expressions and levels of anti-npG IgA, anti-tTG IgA, anti-eTG IgA in DH. However, the IL -6 expression level was significantly lower than that of NE. The lack of correlations suggested no substantial interactions between IL -6, NE, IgA/npG, IgA/tTG or IgA/eTG in DH. Presented results might indicate the heterogenetic nature of DH pathogenesis suggesting further that both autoimmune and autoinflammatory phenomena may be involved in DH cutaneous pathology.

  2. 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

  3. Occupational Exposure to Trichloroethylene and Serum Concentrations of IL-6, IL-10, and TNF-alpha

    Science.gov (United States)

    Bassig, Bryan A.; Zhang, Luoping; Tang, Xiaojiang; Vermeulen, Roel; Shen, Min; Smith, Martyn T.; Qiu, Chuangyi; Ge, Yichen; Ji, Zhiying; Reiss, Boris; Hosgood, H. Dean; Liu, Songwang; Bagni, Rachel; Guo, Weihong; Purdue, Mark; Hu, Wei; Yue, Fei; Li, Laiyu; Huang, Hanlin; Rothman, Nathaniel; Lan, Qing

    2015-01-01

    To evaluate the immunotoxicity of trichloroethylene (TCE), we conducted a cross-sectional molecular epidemiology study in China of workers exposed to TCE. We measured serum levels of IL-6, IL-10, and TNF-α, which play a critical role in regulating various components of the immune system, in 71 exposed workers and 78 unexposed control workers. Repeated personal exposure measurements were taken in workers before blood collection using 3 M organic vapor monitoring badges. Compared to unexposed workers, the serum concentration of IL-10 in workers exposed to TCE was decreased by 70% (P = 0.001) after adjusting for potential confounders. Further, the magnitude of decline in IL-10 was >60% and statistically significant in workers exposed to <12 ppm as well as in workers with exposures ≥ 12 ppm of TCE, compared to unexposed workers. No significant differences in levels of IL-6 or TNF-α were observed among workers exposed to TCE compared to unexposed controls. Given that IL-10 plays an important role in immunologic processes, including mediating the Th1/Th2 balance, our findings provide additional evidence that TCE is immunotoxic in humans. PMID:23798002

  4. Expression of serum MMP-13, TNF-α and IL-6 in patients with chronic hepatitis and liver cirrhosis

    International Nuclear Information System (INIS)

    Xu Zhengfu; Yao Dengfu; Qiu Liwei; Wu Wei; Wu Xinhua; Lu Cuihua

    2005-01-01

    Objective: To detect serum MMP-13, TNF-α and IL-6 levels of the patients with chronic hepatitis B and liver cirrhosis, and evaluate their significant changes. To explore the correlation between serum TNF-α, IL-6 and MMP-13 levels. Method: Double antibody Sandwich Enzyme-Linked Immunosorbent Assay (DAS-ELISA) was used to detect chronic hepatitis in 13 cases, Liver cirrhosis in 28 cases and MMP-13 in the 13 controls, TNF-α in the 20 controls and IL-6 in the 30 controls. Results: Compared with the controls and chronic hepatitis, the serum MMP-13 levels of the patients with liver cirrhosis were significantly higher; the serum TNF-α and IL-6 levels of patients with chronic hepatitis as well as liver cirrhosis were significantly higher; the serum TNF-α and IL-6 levels did not relate to serum MMP-13 in patients with chronic hepatitis and liver cirrhosis. Conclusions: MMP-13 has important effect on formation of liver fibrosis. TNF-α and IL-6 have little effect on expression of MMP-13 levels of the patients with chronic hepatitis and liver cirrhosis. (authors)

  5. Serum levels of interleukin-6 are linked to the severity of the disease caused by Andes Virus.

    Directory of Open Access Journals (Sweden)

    Jenniffer Angulo

    2017-07-01

    Full Text Available Andes virus (ANDV is the etiological agent of hantavirus cardiopulmonary syndrome in Chile. In this study, we evaluated the profile of the pro-inflammatory cytokines IL-1β, IL-12p70, IL-21, TNF-α, IFN-γ, IL-10 and IL-6 in serum samples of ANDV-infected patients at the time of hospitalization. The mean levels of circulating cytokines were determined by a Bead-Based Multiplex assay coupled with Luminex detection technology, in order to compare 43 serum samples of healthy controls and 43 samples of ANDV-infected patients that had been categorized according to the severity of disease. When compared to the controls, no significant differences in IL-1β concentration were observed in ANDV-infected patients (p = 0.9672, whereas levels of IL-12p70 and IL-21 were significantly lower in infected cases (p = <0.0001. Significantly elevated levels of TNF-α, IFN-γ, IL-10, and IL-6 were detected in ANDV-infected individuals (p = <0.0001, 0.0036, <0.0001, <0.0001, respectively. Notably, IL-6 levels were significantly higher (40-fold in the 22 patients with severe symptoms compared to the 21 individuals with mild symptoms (p = <0.0001. Using multivariate regression models, we show that IL-6 levels has a crude OR of 14.4 (CI: 3.3-63.1. In conclusion, the serum level of IL-6 is a significant predictor of the severity of the clinical outcome of ANDV-induced disease.

  6. Clinical significance of measurement of serum NO, IL-6 and IL-8 levels after treatment in patients with schizophrenia

    International Nuclear Information System (INIS)

    Gao Wanqin

    2010-01-01

    Objective: To study the significance of changes of serum NO, IL-6 and IL-8 levels after treatment in patients with schizophrenia. Methods: Serum IL-6, IL-8 (with RIA) and NO (with bio-chemistry) levels were determined in 37 patients with schizophrenia both before and after treatment as well as in 35 controls. Results: Before treatment, the serum IL-6, IL-8 levels in the patients were significantly higher than those in controls (P<0.01). While the serum NO levels were significantly lower (P<0.01). After six weeks' treatment, the levels of IL-6, IL-8 in the patients, though dropped markedly still remained significantly higher (P<0.05) than those in controls. The serum NO levels, though markedly increased after treatment, were still remained significantly lower than those in the controls (P<0.05). Conclusion: Serum NO, IL-6 and IL-8 levels were closely related to the diseases process of schizophrenia and were of prognostic values. (authors)

  7. Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy

    Science.gov (United States)

    Yakabe, Mitsutaka; Ota, Hidetaka; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi; Akishita, Masahiro

    2018-01-01

    Background Interleukin-6 (IL-6) is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear. Methods Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB) and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy. Results Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1) expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice. Conclusion Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy. PMID:29351340

  8. Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy.

    Directory of Open Access Journals (Sweden)

    Mitsutaka Yakabe

    Full Text Available Interleukin-6 (IL-6 is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear.Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy.Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1 expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice.Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy.

  9. Dynamic monitoring of serum IFN-γ, IL-2, and IL-6 contents in patients with Graves' disease

    International Nuclear Information System (INIS)

    Zou Jianwen; Li Weiguo

    2006-01-01

    Objective: To investigate the possible role of cytokines (IFN-γ, IL-2, IL-6) in the pathogenesis of Graves' disease. Methods: Serum FT 3 , FT 4 , TSH (with CLIA), IL-2, IL-6 (with RIA) and IFN-γ (with ELISA) contents were measured in the following subjects: (1) 42 patients with Graves' disease before any treatment, (2) 40 patients in remission after successful treatment with antithyroid drugs (ATD), (3) 25 patients in relapse (around 6 months after cessation of two years' ATD treatment, (4) 40 controls. Results: The serum IFN-γ and IL-6 contents in the patients before treatment and patients in relapse were significantly higher than those in the controls (P 3 , FT 4 levels while the serum IL-2 contents were linearly negatively correlated with FT 3 , FT 4 levels before treatment. Conclusion: Contents of these cytokines fluctuated dynamically along with the status of Graves' disease and might be related to the pathogenesis in some way. (authors)

  10. Study on the changes of serum IL-2, IL-6 and TNF-α levels in patients with chronic glomerulonephritis

    International Nuclear Information System (INIS)

    Xie Jianping; Feng Jiangchao; Zhang Guoyuan; Xiong Gang; Tu Lirong; Xia Chengyun

    2003-01-01

    Objective: To investigate the changes of serum IL-2, IL-6 and TNF-α levels in patients with chronic glomerulonephritis of various types and stages. Methods: Serum IL-2, IL-6 and TNF-α levels were measured with RIA in 71 patients with chronic glomerulonephritis and 36 controls. Results: 1) Serum levels of IL-6 and TNF-α were significantly higher in patients with chronic glomerulonephritis than those in controls (p<0.01) but serum IL-2 levels were significantly lower in the patients (p<0.01). 2)Serum IL-6 and TNF-α levels were positively correlated to BUN levels (p<0.01). 3)There were no significant differences of these cytokines levels among the different types of patients (i.e. general type n=18, nephrotic type n=33 and hypertensive type n=20). Conclusion: These cytokines participated in the pathogenesis of chronic glomerulonephritis. Monitoring the changes of their serum levels was helpful for the management of the disease

  11. Correlation between Interleukin-6 (IL-6, High Sensitivity C-Reactive Protein (hsCRP, Endothelin-1 (ET-1, Asymmetric Dimethylarginine (ADMA and Insulin Resistance (HOMA-IR in Central Obese Men

    Directory of Open Access Journals (Sweden)

    Andri Hidayat

    2011-04-01

    Full Text Available BACKGROUND: Many studies have shown that obesity was closely related to insulin resistance via several pathways such as inflammation, oxidative stress, lipolysis, and endothelial dysfunction. This study was carried out to observe the correlation between inflammation (IL-6 and hsCRP, lipolysis process (ET-1, and endothelial dysfunction (ADMA and insulin resistance (HOMA-IR in centrally obese men. METHODS: This was a cross sectional study on 62 male subjects aged 30–60 years old with waist circumference (WC >90 cm. IL-6, ET-1 and ADMA levels were measured using ELISA method, while hsCRP and insulin were measured using chemiluminescence method. All blood testings were conducted in Prodia Clinical Laboratory. RESULTS: The results showed that WC was significantly correlated with hsCRP (r=0.294, p=0.022, ET-1 (r=0.257, p=0.047 and ADMA (r=0.338, p=0.009. We also found a significant correlation between hsCRP with HOMA-IR (r=0.324, p=0.021, ADMA with HOMA-IR (r=0.280, p=0.045 and IL-6 with hsCRP (r=0.437, p=0.003. CONCLUSIONS: hsCRP and ADMA have significant correlation with HOMA-IR in centrally obese men. HOMA-IR significantly increases in subjects with ADMA above median and either IL-6 or hsCRP above median, as compared to those in the other groups. Inflammation and endothelial dysfunction are important causal pathways of insulin resistance state in centrally obese men. KEYWORDS: obesity, IL-6, hsCRP, ET-1, ADMA, HOMA-IR.

  12. Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis.

    Science.gov (United States)

    Pan, Y W; Zhou, Z G; Wang, M; Dong, J Q; Du, K P; Li, S; Liu, Y L; Lv, P J; Gao, J B

    2016-11-03

    Early detection and treatment is critically important for lung cancer patients. Inflammatory mediators such as IL-6, IL-10, and MCP-1 participate in lung cancer regulation. CEA, CA125, and ProGRP are commonly used serum tumor markers for lung cancer. In this study, we assessed the sensitivity and specificity of CEA, CA125, and ProGRP when used in combination with IL-6, IL-10, and MCP in lung cancer diagnosis. Serum from three different groups (healthy controls, individuals with high risk for lung cancer, and lung cancer patients) was collected. Electrochemiluminescence was used to detect expressions of CEA, CA125, and ProGRP; ELISA was used to examine serum levels of IL-6, IL-10, and MCP-1. Specificity and sensitivity of single as well as combination markers in lung cancer diagnosis were determined. Results indicated that CEA, CA125, ProGRP, and MCP-1 were significantly up-regulated in lung cancer patients as compared to those in controls and high risk individuals. Higher IL-6 and IL-10 levels were observed in both lung cancer patients and high-risk individuals as compared to those in controls. Highest sensitivity (95.2%) in cancer diagnosis was achieved when all six markers were used. This was followed by a combination of IL-6, IL-10, CEA, CA125, and ProGRP (92.6%). The most sensitive (88.6%). Four-marker combination was composed of IL-6, CEA, CA125, and ProGRP. As the combined usage of CEA, CA125, ProGRP, IL-6, IL-10, and MCP-1 significantly improved sensitivity of lung cancer detection; this biomarker arrangement may be beneficial for early diagnosis, treatment, and prognosis of lung cancer.

  13. IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients

    Directory of Open Access Journals (Sweden)

    M.R. Bacci

    2015-05-01

    Full Text Available Community-acquired pneumonia (CAP is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II. The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1 and interleukin-6 (IL-6, tumor necrosis factor alpha (TNF-α, C-reactive protein (CRP, and homocystein were collected at the time of admission (day 1 as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1 to 8 pg/mL (day 7 (P=0.016. The median levels of TNF-α were higher in patients: i with acute kidney injury (AKI (P=0.045, ii requiring mechanical ventilation (P=0.040, iii with short hospital stays (P=0.009, iv admitted to the intensive care unit (ICU (P=0.040, v who died early (P=0.003, and vi with worse CRB scores (P=0.013. In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.

  14. IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients.

    Science.gov (United States)

    Bacci, M R; Leme, R C P; Zing, N P C; Murad, N; Adami, F; Hinnig, P F; Feder, D; Chagas, A C P; Fonseca, F L A

    2015-05-01

    Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.

  15. IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients

    International Nuclear Information System (INIS)

    Bacci, M.R.; Leme, R.C.P.; Zing, N.P.C.; Murad, N.; Adami, F.; Hinnig, P.F.; Feder, D.; Chagas, A.C.P.; Fonseca, F.L.A.

    2015-01-01

    Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI

  16. IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients

    Energy Technology Data Exchange (ETDEWEB)

    Bacci, M.R.; Leme, R.C.P.; Zing, N.P.C. [Departamento de Cliníca Médica, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Murad, N. [Departamento de Cardiologia, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Adami, F.; Hinnig, P.F. [Departamento de Cliníca Médica, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Feder, D. [Departamento de Farmacologia, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Chagas, A.C.P. [Departamento de Cardiologia, Faculdade de Medicina do ABC, Santo André, SP (Brazil); Fonseca, F.L.A. [Departamento de Cliníca Médica, Faculdade de Medicina do ABC, Santo André, SP (Brazil)

    2015-02-24

    Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.

  17. Effects of chemotherapy on changes of serum cytokines (TNF, IL-6, TGF-α) levels in patients with hematologic malignancies

    International Nuclear Information System (INIS)

    Ye Liping; Ye Yixiu; Shi Bing; Liu Lihui; Liu Li

    2005-01-01

    Objective: To study the changes of serum cytokines (TNF, IL-6, TGF-α) levels during chemotherapy in patients with hematologic malignancies. Methods: Serum TNF, IL-6 and TGF-α levels were measured with RIA in 92 patients with hematologic malignancies both before and after chemotherapy as well as in 30 controls. Results: Before chemotherapy, serum levels of TNF and IL-6 were significantly higher in all the patients than those in controls (P<0.01). After chemotherapy at remission, the values dropped considerably (vs before chemotherapy, P<0.01). The serum TGF-α levels before chemotherapy in these patients were also significantly higher than those in controls (P<0.01) with the exception of patients with myelodysplastic syndrome (vs controls, not mach different) and patients with multiple myeloma (significantly lower than those in controls, P<0.01). The values were greatly corrected after chemotherapy in all these patients (vs before chemotherapy, P<0.01). In the patients relapsed (acute leukemia, n=4; chronic myelogenic leukemia, n=4; myelodysplastic syndrome, n=5), the cytokines levels rose abruptly to pre-chemotherapy levels or even higher. Conclusion: Serum TNF, IL-6 and TGF-α levels in patients with hematologic malignancies were closely related to the disease status and were of prognostic value. (authors)

  18. Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

    Science.gov (United States)

    McNearney, Terry A; Sallam, Hanaa S; Hunnicutt, Sonya E; Doshi, Dipti; Chen, Jiande D Z

    2013-01-01

    We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

  19. Effects of flurbiprofen axetil on postoperative serum IL-2 and IL-6 levels in patients with colorectal cancer.

    Science.gov (United States)

    Jiang, W W; Wang, Q H; Peng, P; Liao, Y J; Duan, H X; Xu, M; Li, Y; Zhang, P B

    2015-12-09

    We explored the effects of flurbiprofen axetil on interleukin (IL)-2 and IL-6 levels in postoperative patients with colorectal cancer. A total of 120 patients (American Society of Anesthesiologists I and II) scheduled to undergo colorectal cancer surgery were randomly divided into 3 groups (N = 40 in each group): flurbiprofen axetil group (group F), morphine group (group M), and tramadol group (group T). Group M received 0.1 mg/kg morphine, group T received 1.5 mg/kg tramadol, and group F received 1.5 mg/kg flurbiprofen axetil. Patients in the 3 groups were administered treatments through intravenous injection 10 min before surgery. Serum IL-2 and IL-6 levels were detected. Postoperative adverse reactions were recorded, such as nausea, vomiting, and pruritus. The serum IL-6 level of the 3 groups increased 3 h after surgery. Compared with group M, IL-6 level was higher in group T and group F at 1 day after the surgery, and the differences between group M and the other groups were significant (P Flurbiprofen axetil promoted the secretion of IL-2 and inhibited IL-6; additionally, flurbiprofen axetil may have a lower incidence of adverse reactions compared to other treatments.

  20. 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

  1. Clinical significance of determination of changes of serum GM-CSF, IL-8, IL-6 levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Xue Hongfeng

    2006-01-01

    Objective: To investigate the changes of serum GM-CSF, IL-8 and IL-6 levels both before and after treatment in pediatric patients with bronchial asthma. Methods: Serum GM-CSF, IL-8 and IL-6 levels were measured with RIA in 32 pediatric patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment, the serum GM-CSF, IL-8, IL-6 levels were significantly higher in the patients than those in the controls (P 0.05). Conclusion: Abnormal high serum GM-CSF, IL-8, IL-6 levels played important role in the pathogenesis of bronchial asthma in children. (authors)

  2. Changes of serum levels of some relevant cytokine (IL-2, IL-6, TNF-α) after antithyroid treatment in patients with graves' disease

    International Nuclear Information System (INIS)

    Ren Xiaohua; Jiang Boyong

    2010-01-01

    Objective: To study the effect of antithyroid treatment on the changes of serum levels of IL-2, IL-6 and TNF-α in patients with Graves' disease. Methods: Serum levels of IL-2, IL-6 and TNF-α were measured with RIA in 30 patients with Graves' disease (both before and after treatment with antithyroid drug) and 30 controls. Results: Before treatment serum levels of IL-6 and TNF-α in the patients were significantly higher than those in controls (P 0.05). Conclusion: Changes of serum IL-2, IL-6 and TNF-α levels might be important in the pathogenesis of Graves' disease. (authors)

  3. Clinical significance of measurement of changes of serum IL-6, IL-18 and IL-1β levels after treatment in patients with endometriosis

    International Nuclear Information System (INIS)

    Zhang Chunyan; Zhang Shumin; Zhou Dongxia; Wang Enbo

    2008-01-01

    Objective: To explore the clinical significance of changes of serum IL-6, IL-18 and IL-1β levels after treatment in patients with endometriosis. Methods: Serum IL-6 (with RIA) and IL-18, IL-1β (with ELISA) levels were determined in 38 patients with endometriosis both before and after treatment as well as 35 controls. Results: Before treatment, the serum IL-6, IL- 18 and IL-1β levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum IL-6, IL-18 and IL- 1β levels might reflect the progress of diseases in patients with endometriosis. (authors)

  4. 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.

  5. Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19-9) in gastric cancer

    OpenAIRE

    Łukaszewicz-Zając, Marta; Mroczko, Barbara; Gryko, Mariusz; Kędra, Bogusław; Szmitkowski, Maciej

    2010-01-01

    Gastric cancer (GC) is a second most common cause of cancer-related death and represents an inflammation-driven malignancy. It has been suggested that interleukin 6 (IL-6) and C-reactive protein (CRP) play a potential role in the growth and progression of GC. The aim of the present study was to compare clinical significance of IL-6 and CRP with classic tumor markers—carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in GC patients. The study included 92 patients with GC and 70 ...

  6. Cytokines and Bone Loss in a 5-Year Longitudinal Study—Hormone Replacement Therapy Suppresses Serum Soluble Interleukin-6 Receptor and Increases Interleukin-1-Receptor Antagonist

    DEFF Research Database (Denmark)

    Abrahamsen, B.; Bonnevie-Nielsen, V.; Ebbesen, E.N.

    2000-01-01

    ) and the soluble IL-6 receptor (sIL-6R) potentially modify cytokine bioactivity. We therefore assessed the impact of menopause and hormone replacement therapy (HRT) on cytokines and activity modifiers in serum within a 5-year longitudinal study. One hundred sixty perimenopausal women (age 50.1 +/- 2.8 years) were.......16; p = 0.17). In conclusion, serum IL-1ra and sIL-6R are influenced by HRT and are associated with the rate of bone loss in perimenopausal women....

  7. Clinical significance of changes of serum hs-CRP, IL-6 and TNF-α levels after treatment in patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Yang Wen; Wang Ying

    2010-01-01

    Objective: To explore the clinical significance of changes of serum hs-CRP, IL-6 and TNF-α levels in patients with polycystic ovary syndrome. Methods: Serum hs-CRP (with immuno turbidity method), IL-6, TNF-α (with RIA) levels were determined in 31 patients with polycystic ovary syndrome both before and after six, month's treatment as well as 35 controls. Results: Before treatment, the serum hs-CRP, IL-6 and TNF-α levels in the 31 patients with polycystic ovary syndrome were significantly higher than those in controls (P 0.05). Serum hs-CRP levels were positive correlate with serum IL-6, TNF-α levels (r=0.6014, 0.5982, P<0.01). Conclusion: Serum hs-CRP, IL-6 and TNF-α levels were correlated to the development of polycystic ovary syndrome (PCOS). (authors)

  8. Polymorphism of the NFKB1 affects the serum inflammatory levels of IL-6 in Hashimoto thyroiditis in a Turkish population.

    Science.gov (United States)

    Koc, Arzuhan; Batar, Bahadir; Celik, Ozlem; Onaran, Ilhan; Tasan, Ertugrul; Sultuybek, Gonul Kanigur

    2014-07-01

    Hashimoto thyroiditis (HT) is a chronic inflammatory autoimmune disease of thyroid gland affected by interaction of multiple genes and various cytokines. Variants in the genes coding for the NFKB and IKB proteins can be potentially involved in the development of the inflammatory diseases. NFKB, a key transcription factor of the regulation of immune responses, is interesting candidate for association studies about autoimmune disorder. The aim of the present study was to investigate the relationship between NFKB1 and NFKBIA (NFKB1 inhibitor gene) polymorphisms, and the risk of HT in a Turkish Population in the context of IL-6 serum levels which may contribute to susceptibility to the disease. We analyzed the distribution of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms using PCR-RFLP method and IL-6 serum levels using ELISA method in 120 HT patients and 190 healthy controls in Turkish population. Although, there was no statistical significant difference in distribution of the genotypes and alleles of NFKB1-94ins/del ATTG or NFKBIA 3'UTR A→G polymorphisms in patients and control subjects as single, ins/ins/GG combined genotype had protective effect on the disease when compared to ins/ins/AG combined genotype as combined genotypes of both polymorphisms. In addition to this finding, IL-6 serum levels in HT patients with del/del genotype were significantly higher than in patients with del/ins genotype (p<0.001). According to the combined genotype analysis of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms, IL-6 levels were also higher in patients with del/del genotype when at least one G allele existing (p=0.007). Therefore, our findings suggest that the functional promoter NFKB1-94ins/del ATTG polymorphism was significantly associated with population HT disease through acting by directly modulating IL-6 serum levels. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. Brain-derived neurotrophic factor and interleukin-6 levels in the serum and cerebrospinal fluid of children with viral infection-induced encephalopathy.

    Science.gov (United States)

    Morichi, Shinichiro; Yamanaka, Gaku; Ishida, Yu; Oana, Shingo; Kashiwagi, Yasuyo; Kawashima, Hisashi

    2014-11-01

    We investigated changes in the brain-derived neurotrophic factor (BDNF) and interleukin (IL)-6 levels in pediatric patients with central nervous system (CNS) infections, particularly viral infection-induced encephalopathy. Over a 5-year study period, 24 children hospitalized with encephalopathy were grouped based on their acute encephalopathy type (the excitotoxicity, cytokine storm, and metabolic error types). Children without CNS infections served as controls. In serum and cerebrospinal fluid (CSF) samples, BDNF and IL-6 levels were increased in all encephalopathy groups, and significant increases were noted in the influenza-associated and cytokine storm encephalopathy groups. Children with sequelae showed higher BDNF and IL-6 levels than those without sequelae. In pediatric patients, changes in serum and CSF BDNF and IL-6 levels may serve as a prognostic index of CNS infections, particularly for the diagnosis of encephalopathy and differentiation of encephalopathy types.

  10. Clinical significance of measurement of plasma leptin and serum IL-6, IL-18 levels after treatment in patients with children nephrotic syndrome

    International Nuclear Information System (INIS)

    Wang Xiaoyan

    2011-01-01

    Objective: To explore the clinical significance of changes of plasma leptin and serum IL-6, IL-18 levels after treatment in patients with children nephrotic syndrome. Methods: Plasma leptin (with RIA) serum IL-6, IL-18 (with ELISA) levels were measured in 31 patients with children nephrotic syndrome both before and after treatment as well as in 30 controls. Results: Before treatment,the plasma leptin and serum IL-6, IL-18 levels were significantly higher than those in controls(P <0.01). After treatment for 3 months, the levels in patients though dropped markedly remained significantly higher than those in controls (P<0.05). Plasma leptin levels were positively correlated with IL-6, IL-18 levels (r=0.6138, 0.5784, P<0.01). Conclusion: Changes of plasma leptin and serum IL-6, IL-18 levels after treatment might be of prognostic importance in patients with children nephrotic syndrome. (authors)

  11. 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.

  12. Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

    Science.gov (United States)

    Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

    2015-07-01

    Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Milica Milovan Borovcanin

    2017-11-01

    Full Text Available 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.

  14. Clinical significance of determination of serum IL-2, IL-6 and GM-CSF levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Wang Zhuo; Sun Jin; Yao Li

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IL-2, IL-6 and GM-CSF levels after treatment in pediatric patients with bronchial asthma. Methods: Serum levels of IL-2, IL-6 and GM-CSF were measured with RIA in 36 pediatric patients with bronchiol asthma and 30 controls. Results: Before treatment, the serum levels of IL-6, GM-CSF were significantly higher in the patients than those in controls (P 0.05), Serum IL-2 levels were negatively correlated with the IL-6 and GM-CSF levels (r=-0.5846, -0.6018, P<0.01). Conclusion: These cytokines participated in the pathogenesis of bronchial asthma in pediatric patients. Mornitoring the changes of their serum levels was helpful for the management of the diseases. (authors)

  15. Clinical significance of determination of changes in serum hs-CRP, IL-6, IL-10, and IL-18 levels after treatment in patients with acute conjunctivitis

    International Nuclear Information System (INIS)

    Liu Jun

    2007-01-01

    Objective: To study the clinical significance of changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels in patients with acute conjunctivitis after treatment. Methods: Serum IL-6, IL-10 (with RIA) hs-CRP (with Immuno-turbidity) and IL-18 (with ELISA) levels were measured in 38 patients with acute conjunctivitis both before and after treatment as well as in 35 controls. Results: The serum hs-CRP, IL-6, IL-10 and IL-18 levels in the patients before treatment were significantly higher than those in the controls (P 0.05). Conclusion: Measurement of the changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels after treatment might be inportant for outcome prediction in patients with acute conjunctivitis. (authors)

  16. Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia

    International Nuclear Information System (INIS)

    Wang Guanghui; Chen Chuanbing; Wang Xianwu

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 (with RIA) and hs-CRP (with immunoturbidity method) levels were determined in 36 pediatric patients with bronchopneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and hs-CRP levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Determination of serum IGF-II, IL-6, IL-8 and hs-CRP levels in pediatric patients with bronchopneumonia was important for diagnosis and outcome prediction. (authors)

  17. Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8, TNF-α levels after treatment in children with bronchopneumonia

    International Nuclear Information System (INIS)

    Feng Yue

    2011-01-01

    Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and TNF-α levels after treatment in children with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 and TNF-α levels with RIA were detected both before and after treatment in 33 patients with children bronchopneumonia as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and TNF-α levels were significantly higher in the patients than those in the controls (P 0.05). Conclusions: Serum IGF-II, IL-6, IL-8 and TNF-α could take part in the pathogenesis of children bronchopneumonia in various ways and determination of these levels was clinically important. (authors)

  18. Clinical significance of determination of changes of serum IL-6, IL-8, IL-10 and IL-18 levels after treatment in patients with chronic renal diseases

    International Nuclear Information System (INIS)

    Liu Congjiang; Li Fen; Zhang Lei; Liu Jianhua

    2008-01-01

    Objective: To explore the changes of serum IL-6, IL-8, IL-10 and IL-18 levels after treatment in patients with chronic renal diseases. Methods: Serum IL-6, IL-8, IL-10 levels were determined with RIA and IL-18 levels with ELISA in 32 patients with chronic renal diseases both before and after treatment as well as in 35 controls. Results: Before treatment the serum IL -6, IL-8, IL-10 and IL-18 levels were significantly higher in the patients than those in controls (P<0.01). After 6 months of treatment, the levels though dropped markedly remained significantly higher (P<0.05). Conclusion: Levels of serum IL-6, IL- 8, IL-10 and IL-18 increased significantly in patients with chronic renal diseases, especially in those advanced cases. (authors)

  19. Clinical significance of determination of changes of serum IL-6, IL-10 and GM-CSF levels after treatment in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Qin Wenjing

    2008-01-01

    Objective: To explore the changes of Serum IL-6, IL-10 and GM-CSF levels after treatment in pediatric patients with bronchial asthma. Methods: Serum IL-6, IL-10 and GM-CSF levels were measured with RIA in 33 pediatric patients with bronchial asthma both before and after treatment as well as in 30 controls. Results: Before treatment, the serum IL-6, IL-10 and GM-CSF levels were significantly higher than those in controls (P 0.05). Conclusion: Detection of serum IL-6, IL-10 and GM-CSF levels were useful for assessment of therapeutic efficacy and were of important clinical values in pediatric patients with bronchial asthma. (authors)

  20. Clinical significance of measurement of changes of serum hs-CRP, IL-6, IL-8 M-CSF levels after treatment in patients with endometriosis

    International Nuclear Information System (INIS)

    Chen Xiaochao; Zhou Dongxia; Zhang Limin; Liu Hongshu

    2008-01-01

    Objective: To explore the significance of changes of serum hs-CRP, IL-6, IL-8 and M-CSF levels after treatment in patients with endometriosis. Methods: Serum IL-6, IL-8, M -CSF(with RIA), hs-CRP(with immuneturbidity method)levels were determined in 33 patients with endometriosis both before and after treatment as well as in 35 controls. Results: Before treatment, the serum hs-CRP, IL-6, IL-8 and M-CSF levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum hs-CRP, IL-6, IL-8 and M-CSF levels might reflect the progress of diseases in patients with endometriosis. (authors)

  1. Effects of Shugan Jieyuling self-made on behavior and levels of serum IL-2, IL-6 and cortisol in depression models

    International Nuclear Information System (INIS)

    Li Qiubo; Yao Di; Zhang Ping; Li Youtian; Xu Dan; Jiang Sailin; Xu Caiyun

    2005-01-01

    Objective: To study the effects of Shugan Jieyuling self-made (SJSM) on behavior, levels of serum IL-2, IL-6 and cortisol in depression model mice. Methods: The adult mice separately raised and treated with chronic unpredictable middle stress stimulus were used to establish depression models. The curative effect of SJSM was observed in depression model mice. The changes of weight and behavior were detected in a period. Radioimmunoassay (RIA) was used to examine the contents of serum IL-2, IL-6 and cortisol levels. Results: The increased weights of the depression model mice were declined compared with the normal mice before administration. The mental state and behavior of the depression mice were changed. The mice were starling, dreadful, helpless and immobile. At the same time the contents of serum IL-2, IL-6 and cortisol were obviously lower than those of the normal mice. SJSM (large and low doses) and Baiyoujie changed the increased weights and behaviors of the depression after administration for 21 d. The mental state was meliorated simultaneously, and the serum IL-2, IL-6 and cortisol levels in the depression model mice were decreased significantly compared with normal mice. Conclusion: The levels of serum IL-2, IL-6 and cortisol may be the guideline for the diagnosis of depression disease. SJSM can obviously improve both the symptoms of the depression models and the levels of serum IL-2, IL-6 and cortisol. (authors)

  2. Effect of low-dose ketamine on post-operative serum IL-6 production ...

    African Journals Online (AJOL)

    Department of Anaesthesia Mulago National Referral Hospital's ... Materials and methods: Institutional Review Board's approval was sought and RCT was ... Blood samples were collected and laboratory analyzed at baseline, ... The greater the surgical trauma, the greater the serum ..... Plasma, urine, and cerebrospinal fluid.

  3. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice

    Directory of Open Access Journals (Sweden)

    Margarita Vida

    2015-07-01

    Full Text Available Interleukin-6 (IL-6 has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD in wild-type (WT and IL-6-deficient (IL-6−/− mice. Additionally, HFD-fed IL-6−/− mice were also chronically treated with recombinant IL-6 (rIL-6. Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1 and signal transducer and activator of transcription-3 (STAT3, increased AMP kinase phosphorylation (p-AMPK, and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS and stearoyl-CoA desaturase 1 (SCD1. The HFD-fed IL-6−/− mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β, FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6−/− mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis.

  4. Clinical significance of measurement of changes of serum TNF-α, IL-6 and IL-8 centent after treatment in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Wang Guiying

    2008-01-01

    Objective: To explore the clinical significance of changes of serum TNF-α, IL-6 and IL-8 levels in patients with pregnancy induced hypertension. Methods: Serum TNF-α, IL-6 and IL-8 levels were measured with RIA in 36 patients with pregnancy induced hypertension both before and after 2 weeks of treatment as well as in 35 controls. Results: Before treatment, the serum TNF-α, IL-6 and IL-8 levels were significantly higher in patients with PIH than those in the controls (P 0.05). Conclusion: The inflammatory cytokines such as TNF-α, IL-6 and IL-8 may play important roles in the pathogenesis of pregnancy induced hypertension. (authors)

  5. Clinical significance of measurement of changes of serum TNF-α, IL-6 levels in patients with chronic congestive heart failure

    International Nuclear Information System (INIS)

    Yang Chun; Gu Ling; Zhang Yanjun; Huang Rongchong; Lu Yan

    2006-01-01

    Objective: To study the clinical significance of the detection of changes of serum TNF-α and IL-6 levels in patients with chronic congestive heart failure. Methods: The serum levels of TNF-α and IL-6 were determined with RIA in 176 patients with chronic heart failure (CHF) and 30 controls. Results: The serum levels of TNF-α and IL-6 in patients with CHF were significantly higher than those in controls (P<0.05). The levels increased along with the increase of severity of cardiac failure. The levels in patients with cardiac function of any grade were significantly different from those in patients with another grade of cardiac function. Conclusion: Immunological activation and myocardial inflammation exist in CHF patients. The increasing levels of TNF-α and IL-6 can trigger the onset and development of CHF. (authors)

  6. Observations on the relationship between the levels of serum IL-6 and TNF-α and the severity of diabetic retinopathy and curative effect in cataract extraction with intraocular lens implantation in diabetics

    International Nuclear Information System (INIS)

    Wang Yumin; Ma Xinying; Song Yuebing; Liang Yong; Zhang Xiaoguang

    2001-01-01

    Objective: To determine the sequential changes of blood levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in diabetics with extracapsular extraction and posterior chamber intraocular lens implantation and to study their correlation with curative effects and pos-operative complications. Methods: The serum concentrations of IL-6 and TNF-α in 39 diabetics and non-diabetics were measured by radioimmunoassay at preoperative, post-operative and on days 7, 14 and 90 postoperatively. Results: There was significant difference in the levels of the two factors between the diabetic group and non-diabetic group preoperatively (P<0.05). The serum levels of the two factors in patients with proliferative diabetic retinopathy were higher than those in non-diabetic retinopathy, and simple diabetic retinopathy post-operative (P<0.01). Post-operative complication rate was higher in patients with proliferative diabetic retinopathy than those without retinopathy and those having simple diabetic retinopathy. Conclusion: The levels of the two factors correlate with complications and curative effect of patients with proliferative diabetic retinopathy undergoing intraocular lens implantation

  7. 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.

  8. Diagnostic value of combined determination of serum and chest fluid adenosine deaminase (ADA), IL-2, IL-6, IL-10 contents for differentiation of tuberculous from malignant pleural effusion

    International Nuclear Information System (INIS)

    Wu Jiaming; Wang Limin

    2005-01-01

    Objective: To investigate the possible diagnostic value of combined determination of serum and chest fluid contents of ADA, IL-2, IL-6, IL-10 in patients with tuberculous and malignant pleural effusion. Methods: Serum and chest fluid ADA (with biochemical method), IL-2, IL-6, IL-10 (with ELISA) contents were measured in 56 patients with tuberculosis pleural effusion, 53 patients with malignant effusion and 30 controls (in serum only). The receiving operative characteristic (ROC) curve for each parameter was analyzed for study of respective area under curse (Auc). Results: The serum IL-6 levels in both groups of patients were significantly higher than those in the controls (P<0.05). The chest fluid contents of ADA, IL-2, IL-6 and IL-10 in patients with tuberculous effusion were all significantly higher than those in patients with malignancies (P<0.05). The Auc in the ROC was largest in the case of ADA, followed by IL-10, IL-6 with IL-2 the least. Conclusion: Determination of chest fluid ADA, IL-2, IL-6, IL-10 contents was helpful in the differentiation of tuberculous from malignant pleural effusion. Combined determination of chest fluid ADA and IL-10 provided the highest accuracy rate for differentional diagnosis. (authors)

  9. Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology patients with neutropenia and fever for the assessment of low-risk

    Directory of Open Access Journals (Sweden)

    Kontny Udo

    2008-03-01

    Full Text Available Abstract Background Patients with chemotherapy-related neutropenia and fever are usually hospitalized and treated on empirical intravenous broad-spectrum antibiotic regimens. Early diagnosis of sepsis in children with febrile neutropenia remains difficult due to non-specific clinical and laboratory signs of infection. We aimed to analyze whether IL-6 and IL-8 could define a group of patients at low risk of septicemia. Methods A prospective study was performed to assess the potential value of IL-6, IL-8 and C-reactive protein serum levels to predict severe bacterial infection or bacteremia in febrile neutropenic children with cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test, Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating Characteristics. Results The analysis of cytokine levels measured at the onset of fever indicated that IL-6 and IL-8 are useful to define a possible group of patients with low risk of sepsis. In predicting bacteremia or severe bacterial infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42 pg/ml showing a high sensitivity (90% and specificity (85%. Conclusion These findings may have clinical implications for risk-based antimicrobial treatment strategies.

  10. Study on the changes of serum TNF-α, IL-1β, IL-6 and IL-8 levels in patients with coronary cardiac heart diseases

    International Nuclear Information System (INIS)

    Lu Xiaozhuo; Yu Xian

    2003-01-01

    Objective: To study the role TNF-α, IL-1β, IL-6 and IL-8 played in the pathogenesis of coronary cardiac heart diseases. Methods: Serum levels of TNF-α, IL-1β, IL-6 and IL-8 levels were determined by chemiluminescence immunoassay in 32 patients with stable angina, 39 patients with acute myocardial infarction and 36 controls. Results: Serum TNF-α, IL-1β, IL-6 and IL-8 levels in all patients were higher than those in controls. Remarkably increased level were seen in acute myocardial infarction group. Difference between control and patient groups were: stable angina group TNF-α, p<0.05, IL-6, p<0.01 and IL-8, p<0.05; acute myocardial infarction group TNF-α, p<0.01, IL-1β, p<0.05, IL-6, p<0.001 and IL-8, p<0.001. Conclusion: There is close relationship between serum TNF-α, IL-1β, IL-6, IL-8 levels and development of coronary cardiac heart disease. They play an important role in the pathogenesis through mutual induction and synergistic actions

  11. 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.)

  12. Clinical significance of determination of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis

    International Nuclear Information System (INIS)

    Wang Tongwu

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis. Methods: Serum IL-6, saliva secretory IgA (with RIA) and serum hs-CRP (with immuno-tarbility method) levels were measured in 42 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment serum IL-6, hs-CRP and saliva secretory IgA levels in the patients wree significantly higher than those in controls (P 0.05). However, the saliva secreatory IgA levels were still significantly higher than those in controls (P<0.05). Conclusion: There was disturbance of immunomodulation in patients with periodontitis as expressed by the changes of cytokines levels in the course of the diseases. (authors)

  13. Clinical significance of changes of serum IL-2, IL-6 and gastrin levels before and after treatment in patients with chronic eczema

    International Nuclear Information System (INIS)

    Mou Xudong; Ren Hong

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IL-2, IL-6 and gastrin levels after treatment in patients with chronic eczema. Methods: Serum IL-2, IL-6 and gastin were detected with RIA both before and after treatment in 38 patients with chronic eczema and 35 controls. Results: Before treatment, serum IL-2 levels in the patients were significantly lower than those in the controls (P 0.05), however, the IL-2 levels were still significantly lower than those in controls (P>0.05). Conclusion: Serum IL-2, IL-6 and gastrin levels in the patients with chronic eczema were closely related to the severity of the diseases process and could be taken as indicator of treatment efficacy. (authors)

  14. CHANGES IN SERUM LEVELS OF IL-6 IN THE EARLY POSTOPERATIVE PERIOD AFTER PREEMPTIVE ANALGESIA WITH NIMESULIDE, METAMIZOLE SODIUM AND PLACEBO IN REMOVAL OF IMPACTED MANDIBULAR THIRD MOLARS

    Directory of Open Access Journals (Sweden)

    Deyan Zdravkov Neychev

    2016-08-01

    Full Text Available Abstract Objective: The objective of this study is to determine the change in IL-6 serum levels in patients undergoing preemptive analgesia and surgical removal of an impacted mandibular third molar. Study Design: This is a prospective, double-blind, placebo-controlled study in 80 patients who had an atypical extraction of an impacted mandibular third molar. Results: After surgical removal of impacted mandibular third molars, elevated levels of IL-6 in the early postoperative period were found, and the highest level was 14 pg/ml. Conclusion: Postoperative IL-6 levels rise regardless of the medication used for preemptive analgesia. In the group treated with nimesulide, a trend to reducing IL-6 levels was observed, but further study in a larger number of patients is needed.

  15. Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

    Science.gov (United States)

    Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

    2011-01-01

    Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14 th and 21 st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

  16. [Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

    Science.gov (United States)

    Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

    2016-01-01

    To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (Pprostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (Pprostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

  17. Clinical significance of changes of serum IL-2, IL-6 and TNF-α levels after treatment in patients with periodontitis

    International Nuclear Information System (INIS)

    Wei Dong

    2005-01-01

    Objective: To investigate the changes of serum IL-2, IL-6 and TNF-α levels after one month of comprehensive treatment in patients with periodontitis. Methods: Serum IL-2, IL-6 and TNF-α levels were measured with RIA in 48 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, serum levels of IL-6, TNF- α in the patients were significantly higher and IL-2 levels were significantly lower than those in the controls (both P 0.05). However, the IL-2 levels were still significantly lower than those in controls (P<0.05). Conclusion: There was disturbance of immuno-modulation in patients with periodontitis as expressed by the changes of cytokines levels in the course of the disease. (authors)

  18. 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.)

  19. 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 ...

  20. Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population

    Directory of Open Access Journals (Sweden)

    Rajendran Karthick

    2012-08-01

    Full Text Available Abstract Background Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6 and high sensitivity - C reactive protein (hs-CRP. Results Serum leptin levels were significantly higher in AMI patients when compared to Non-CVD controls. IL-6 and hs-CRP were also elevated in the AMI group and leptin correlated positively with IL-6 and hs-CRP. Incidentally this is the first report from Chennai based population, India. Conclusions The strong correlation between serum levels of leptin and IL-6 implicates an involvement of leptin in the upregulation of inflammatory cytokines during AMI. We hypothesise that the increase in values of IL-6, hs-CRP and their correlation to leptin in AMI patients could be due to participation of leptin in the signaling cascade after myocardial ischemia.

  1. Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population.

    Science.gov (United States)

    Rajendran, Karthick; Devarajan, Nalini; Ganesan, Manohar; Ragunathan, Malathi

    2012-08-14

    Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD) including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI) patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product) is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6) and high sensitivity - C reactive protein (hs-CRP). Serum leptin levels were significantly higher in AMI patients when compared to Non-CVD controls. IL-6 and hs-CRP were also elevated in the AMI group and leptin correlated positively with IL-6 and hs-CRP. Incidentally this is the first report from Chennai based population, India. The strong correlation between serum levels of leptin and IL-6 implicates an involvement of leptin in the upregulation of inflammatory cytokines during AMI. We hypothesise that the increase in values of IL-6, hs-CRP and their correlation to leptin in AMI patients could be due to participation of leptin in the signaling cascade after myocardial ischemia.

  2. study on the serum levels of E2, IL-6 and IGF-I in patients with post-menopausal osteoporosis (PMO)

    International Nuclear Information System (INIS)

    Lv Kuan; Liu Chunyu; Lu Yingju

    2006-01-01

    Objective: To study the changes of serum levels of E 2 , IL-6, IGF-I in patients with post-menopausal osteoporosis (PMO). Methods: Serum levels of E 2 (with CLIA), IL-6, IGF-I, BGP (with RIA) were measured in the following subjects: (1) 32 patients with PMO (2) 32 post-menopausal women without PMO and (3) 30 pre-menopausal controls. Serum P, Ca and AKP levels were also determined. Results: As a whole, serum levels of IL -6 in postmenopausal women were higher than those in controls. Levels in subjects with PMO were significantly higher than those without PMO (P 2 and BMD index (r=-0. 587, - 0. 438 respectively, P 2 and BMD index (r=0.569, 0.433 respectively, P 2 levels will in someway promote the expression of IL-6 ( osteoclastic) and reduce the expression of IGF-I (osteoclastic), resulting in lessening of bone mass. HRT, despite of the controversy over cardio-vascalar safety, is beneficial for osteoporosis. (authors)

  3. Effect of IL-6 on proliferation and IG production of human EBV-transformed cell lines in serum free culture media

    NARCIS (Netherlands)

    Jochems, G. J.; Jordens, R.; van Lier, R. A.; Zeijlemaker, W. P.

    1990-01-01

    To optimalize growth and Ig production of EBV transformed B cells for large scale tissue culture, we analyzed five stable monoclonal EBV-B cell lines for their responsiveness to interleukin (IL)-6 in standard medium with 5% FCS and in several serum-free media. As we previously demonstrated these

  4. [The study on the changes of serum IL- 6, TNF-α and peripheral blood T lymphocyte subsets in the pregnant women during perinatal period].

    Science.gov (United States)

    Li, Juan

    2011-03-01

    To study the change law of serum IL-6, TNF-α and peripheral blood T lymphocyte subsets in the pregnant women during perinatal period. 100 pregnant women in our hospital from November 2009 to October 2010 were selected as research object, and the serum IL-6, TNF-α and peripheral blood T lymphocyte subsets be-fore and at labor onset occurring, after delivery at the first and third day were analyzed and compared. According the study, the serum IL-6 and TNF-aat labor onset occurring were higher than those before labor onset and af-ter delivery at the first and third day , the CD3(+), CD4 (+), CD8(+) and CD4/CD8 decreased first and then increased, all P < 0. 05, there were significant differences. The changes of serum IL-6, TNF-α and peripheral blood T lymphocyte subsets in the pregnant women during perinatal period has a regular pattern, and it is worthy of.

  5. Role of interleukin-6 and pentraxin 3 as an early marker in Peyronie’s disease

    Directory of Open Access Journals (Sweden)

    Arda Atar

    2017-04-01

    Full Text Available Inflammation is mechanistically involved in the development of Peyronie’s disease (PD. The aim of this study is to assess the relevance of serum pentraxin 3 (PTX3 and interleukin-6 (IL-6 concentrations in PD. The study enrolled 40 patients with PD in the acute phase and 40 healthy controls. Plasma PTX3 and IL-6 concentrations were evaluated in 40 patients in the acute phase of PD and 40 healthy controls by enzyme-linked immunosorbent assay. Serum concentrations of both PTX3 and IL-6 were significantly higher in the PD patients than in the control group (p=0.001 and p=0.001, respectively. There was a significant correlation between concentration of PTX3 and painful erections. IL-6 concentrations were significantly higher in patients with erectile dysfunction. IL-6 and PTX3 levels showed no correlation with age, serum C-reactive protein, degree of curvature, and disease duration. IL-6 trans-signaling and PTX3 amplification at the site of inflammation could have a role in pathophysiological mechanisms of PD. Biological drugs may be used for treatment during the acute phase of the disease based on this mechanism.

  6. Effects of different types of anaesthesia (regional vs general) on serum IL-6, IL-8 and M-CSF levels in surgical patients

    International Nuclear Information System (INIS)

    Xiao Jiawang

    2009-01-01

    Objective: To study the effect of anesthesia(regional vs general) on serum IL-6, IL-8 and M-CSF levels in surgical patients. Methods: Serum IL-6, IL-8 and M-CSF levels were determined with RIA 3 times in 34 patients operated under ragional anesthesia and 34 patients operted under general anesthesia (both for benign gastral ulcer). The levels were measured before induction of anesthesia, at beginning of operation and 1 hr later. Results: In patients under regional anesthesia, the IL-6, IL-8 and M-CSF levels increased significantly at the beginning of operation and 1 hr later. Though dropped remained significantly higher than the levels before induction (P<0.05); No significant change of the levels were obsorved in patients under general anesthesia through the operation, and the levels were as a whole significantly lower than the levels under regional anesthesia (P<0.05). Conclusion: General anesthesia (combined intravenous and inhalation) could abolish increases of serum IL-6, IL-8 and M-CSF levels during operation must be of clinical values. (authors)

  7. Associations of IL6 polymorphisms with lung function decline and COPD

    Science.gov (United States)

    He, Jian-Qing; Foreman, Marilyn G.; Shumansky, Karey; Zhang, Xuekui; Akhabir, Loubna; Sin, Don D; Man, S F Paul; DeMeo, Dawn L.; Litonjua, Augusto A.; Silverman, Edwin K.; Connett, John E; Anthonisen, Nicholas R; Wise, Robert A; Paré, Peter D; Sandford, Andrew J

    2010-01-01

    Background Interleukin-6 (IL6) is a pleiotropic pro-inflammatory and immunomodulatory cytokine which likely plays an important role in the pathogenesis of COPD. There is a functional single nucleotide polymorphism (SNP), −174G/C, in the promoter region of IL6. We hypothesized that IL6 SNPs influence susceptibility for impaired lung function and COPD in smokers. Methods Seven and 5 SNPs in IL6 were genotyped in two nested case-control samples derived from the Lung Health Study (LHS) based on phenotypes of rate of decline of forced expiratory volume in one second (FEV1) over 5 years and baseline FEV1 at the beginning of the LHS. Serum IL6 concentrations were measured for all subjects. A partially overlapping panel of 9 IL6 SNPs was genotyped in 389 COPD cases from the National Emphysema Treatment Trial (NETT) and 420 controls from the Normative Aging Study (NAS). Results In the LHS, three IL6 SNPs were associated with FEV1 decline (0.023 ≤ P ≤ 0.041 in additive models). Among them the IL6_−174C allele was associated with rapid decline of lung function. The association was more significant in a genotype-based analysis (P = 0.006). In the NETT-NAS study, IL6_−174G/C and four other IL6 SNPs, all of which are in linkage disequilibrium with IL6_−174G/C, were associated with susceptibility to COPD (0.01 ≤ P ≤ 0.04 in additive genetic models). Conclusion Our results suggest that the IL6_−174G/C SNP is associated with rapid decline of FEV1 and susceptibility to COPD in smokers. PMID:19359268

  8. [Effect of oral intervention on matrix metalloproteinase-2, 9 expression in carotid arteries and serum interleukin-6 in rats with chronic periodontitis].

    Science.gov (United States)

    Li, Jieting; Liu, Yujiao; Ren, Xiuyun; Chang, Le; Yue, Zijie; Shi, Xuexue

    2014-09-01

    To establish chronic periodontitis model in SD rats, and to investigate the effect of oral intervention on atherosclerosis. Fifty male SD rats were randomly divided into three groups, group A (normal control), group B (atherosclerosis,As) and group C (chronic periodontitis, CP). Group C was further divided into group C1 (natural process), group C2 (simple mechanical treatment), group C3 (systemic antibiotics), group C4-1 (teeth extraction) and group C4-2 (teeth extraction+systemic antibiotics), each group consisted of 7 rats. Every group received oral intervention. Serum interleukin (IL)- 6 levels were detected in five different time points (1, 3, 5, 7, 9 weeks after a successful modeling) by enzyme linked immunosorbent assay. All animals were killed after 24 weeks. Matrix metalloproteinase (MMP)- 2, 9 in the proximal aorta was detected by immuno histochemistry. The levels of serum IL-6 in groups B and C1 increased gradually with time and became significantly higher than that in group A (P Periodontitis could increase the risk of atherosclerosis in rats with chronic periodontitis. Periodontal mechanical treatment and teeth extraction may increase the risk of As in the short time. However, the risk would gradually reduce in a long time.

  9. Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a levels in human subjects with rheumatoid diseases.

    Directory of Open Access Journals (Sweden)

    Olaf Schultz

    2010-12-01

    Full Text Available Interleukin-6 (IL-6 is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab.11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a (Lp (a were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a levels significantly decreased.Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a serum levels, which might reduce the cardiovascular risk of human subjects.

  10. Study on the relationship between serum IL-6, Sgp80, Sgp130 levels and bone metabolism in patients with Graves' disease

    International Nuclear Information System (INIS)

    Liu Chunyu; Mu Junqing; Zou Jianwen; Liu Songtao

    2007-01-01

    Objective: To investigate the relationship between serum IL-6, Sgp80, Sgpl30 levels and bone metabolism in patients with Graves' disease. Methods: Serum levels of IL-6 (with RIA), Sgp80, Sgpl30 (with ELISA) as well as BMD of proximal femur region were determined in 78 patients with Graves' disease (26 not treated yet, 26 partially remitted and 26 in remission) and 30 controls. Results: The serum IL-6 and Sgpl30 levels in all the patients with Graves' disease were significantly higher than those in controls (P 3 , FT 4 , phosphorous, BGP and urinary hydroxy proline levels. BMD of the proximal femur region in patients partially remitted were much lower than that in controls (P<0.05). Conclusion: Serum Sgp80 level might be taken as an important parameter in studying of Graves' disease. Bone loss, both cortical and trabecular, occurred in patients with Graves' disease. Increase of bone formation as well as bone resorption were primary, not secondary to each other. (authors)

  11. Upregulation of genes related to bone formation by γ-amino butyric acid and γ-oryzanol in germinated brown rice is via the activation of GABAB-receptors and reduction of serum IL-6 in rats.

    Science.gov (United States)

    Muhammad, Sani Ismaila; Maznah, Ismail; Mahmud, Rozi; Zuki, Abu Bakar Zakaria; Imam, Mustapha Umar

    2013-01-01

    Osteoporosis and other bone degenerative diseases are among the most challenging non-communicable diseases to treat. Previous works relate bone loss due to osteoporosis with oxidative stress generated by free radicals and inflammatory cytokines. Alternative therapy to hormone replacement has been an area of interest to researchers for almost three decades due to hormone therapy-associated side effects. In this study, we investigated the effects of gamma-amino butyric acid (GABA), gamma-oryzanol (ORZ), acylated steryl glucosides (ASG), and phenolic extracts from germinated brown rice (GBR) on the expression of genes related to bone metabolism, such as bone morphogenic protein-2 (BMP-2), secreted protein acidic and rich in cysteine (SPARC), runt-related transcription factor 2 (RUNX-2), osteoblast-specific transcription factor osterix (Osx), periostin, osteoblast specific factor (Postn), collagen 1&2 (Col1&2), calcitonin receptor gene (CGRP); body weight measurement and also serum interleukin-6 (IL-6) and osteocalcin, in serum and bone. Rats were treated with GBR, ORZ, GABA, and ASG at (100 and 200 mg/kg); estrogen (0.2 mg/kg), or remifemin (10 and 20 mg/kg), compared to ovariectomized non-treated group as well as non-ovariectomized non-treated (sham) group. Enzyme-linked immunosorbent assay was used to measure the IL-6 and osteocalcin levels at week 2, 4, and 8, while the gene expression in the bone tissue was determined using the Genetic Analysis System (Beckman Coulter Inc., Brea, CA, USA). The results indicate that groups treated with GABA (100 and 200 mg/kg) showed significant upregulation of SPARC, calcitonin receptor, and BMP-2 genes (P < 0.05), while the ORZ-treated group (100 and 200 mg/kg) revealed significant (P < 0.05) upregulation of Osx, Postn, RUNX-2, and Col1&2. Similarly, IL-6 concentration decreased, while osteocalcin levels increased significantly (P < 0.05) in the treated groups as compared to ovariectomized non-treated groups. GABA and ORZ from

  12. SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

    Science.gov (United States)

    Gregoric, Pavle; Pavle, Gregoric; Sijacki, Ana; Ana, Sijacki; Stankovic, Sanja; Sanja, Stankovic; Radenkovic, Dejan; Dejan, Radenkovic; Ivancevic, Nenad; Nenad, Ivancevic; Karamarkovic, Aleksandar; Aleksandar, Karamarkovic; Popovic, Nada; Nada, Popovic; Karadzic, Borivoje; Borivoje, Karadzic; Stijak, Lazar; Stefanovic, Branislav; Branislav, Stefanovic; Milosevic, Zoran; Zoran, Milosević; Bajec, Djordje; Djordje, Bajec

    2010-01-01

    Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.

  13. 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

    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...... in serum CXCL-1 (5-fold) and liver CXCL-1 mRNA expression (24-fold) compared with control. Because IL-6 expression and release are known to be augmented during exercise in glycogen-depleted animals, CXCL-1 and IL-6 expression were examined after exercise in overnight-fasted mice.We found that fasting...... 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....

  14. 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.

  15. Relationship among IL-6, LDL cholesterol and lipid peroxidation.

    Science.gov (United States)

    Lubrano, Valter; Gabriele, Morena; Puntoni, Maria Rita; Longo, Vincenzo; Pucci, Laura

    2015-06-01

    Previous studies evidenced a significant reduction in serum cholesterol levels during an episode of acute inflammation. The aim of the present study was to verify the hypothesis of a regulatory role of cytokines through an in vitro model that simulates a situation of vascular inflammation and high levels of LDL or lipoperoxides. Human microvascular endothelial cells-1 were used in all experiments. The cells were exposed for 24 h to increasing doses of LDL, oxidized lipoprotein, and 8-isoprostane (in the absence or presence of SQ29.548, a TXA2 receptor antagonist). Moreover, LDL receptor and oxidized lipoprotein receptor expression analyzed after endothelial cells' incubation with increasing doses of interleukin-6. The ELISA test and quantitative real-time PCR were performed. Endothelial cells showed a significant increase in interleukin-6 medium levels associated with LDL, oxidized LDL and with the degree of oxidation (absence or presence of SQ29.548), while 8-isoprostane did not. Treatment of human microvascular endothelial cells-1 for 24 h with increasing doses of interleukin-6 significantly enhanced LDL receptor and oxidized lipoprotein receptor-1 mRNA expression. Our data suggest the presence of a compensatory mechanism. The induction of a significant increase of IL-6 does not seem to be caused by the presence of the biological activity of 8-isoprostane.

  16. IL-6 and mouse oocyte spindle.

    Directory of Open Access Journals (Sweden)

    Jashoman Banerjee

    Full Text Available Interleukin 6 (IL-6 is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001 as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.

  17. Interleukin-6 and procalcitonin as biomarkers in mortality prediction of hospitalized patients with community acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Ilija Andrijevic

    2014-01-01

    Full Text Available Introduction: Community acquired pneumonia (CAP may present as life-threatening infection with uncertain progression and outcome of treatment. Primary aim of the trial was determination of the cut-off value of serum interleukin-6 (IL-6 and procalcitonin (PCT above which, 30-day mortality in hospitalized patients with CAP, could be predicted with high sensitivity and specificity. We investigated correlation between serum levels of IL-6 and PCT at admission and available scoring systems of CAP (pneumonia severity index-PSI, modified early warning score-MEWS and (Confusion, Urea nitrogen, respiratory rate, Blood pressure, ≥65 years of age-CURB65. Methods: This was prospective, non-randomized trial which included 101 patients with diagnosed CAP. PSI, MEWS and CURB65 were assessed on first day of hospitalization. IL-6 and PCT were also sampled on the first day of hospitalization. Results: Based on ROC curve analysis (AUC ± SE = 0.934 ± 0.035; 95%CI(0.864-1.0; P = 0.000 hospitalized CAP patients with elevated IL-6 level have 93.4% higher risk level for lethal outcome. Cut-off value of 20.2 pg/ml IL-6 shows sensitivity of 84% and specificity of 87% in mortality prediction. ROC curve analysis confirmed significant role of procalcitonin as a mortality predictor in CAP patients (AUC ± SE = 0.667 ± 0.062; 95%CI(0.546-0.789; P = 0.012. Patients with elevated PCT level have 66.7% higher risk level for lethal outcome. As a predictor of mortality at the cut-off value of 2.56 ng/ml PCT shows sensitivity of 76% and specificity of 61.8%. Conclusions: Both IL-6 and PCI are significant for prediction of 30-day mortality in hospitalized patients with CAP. Serum levels of IL6 correlate with major CAP scoring systems.

  18. Comparison between preoperative administration of methylprednisolone with its administration before and during congenital heart surgery on serum levels of IL-6 and IL-10.

    Science.gov (United States)

    Abbasi Tashnizi, Mohammad; Soltani, Ghasem; Moeinipour, Ali Asghar; Ayatollahi, Hossein; Tanha, Amir Saber; Jarahi, Lida; Sepehri Shamloo, Alireza; Zirak, Nahid

    2013-02-01

    Steroid administration during cardiopulmonary bypass is considered to improve cardiopulmonary function by modulating inflammations caused by bypass. This study was performed to compare effectiveness of preoperative and intraoperative methylprednisolone (MP) to preoperative methylprednisolone alone in post bypass inflammatory (IL-6) and anti-inflammatory (IL-10) factors. Fifty pediatric patients undergoing cardiopulmonary bypass surgery from August 2011 to 2012 in the cardiac surgery department of Imam Reza Hospital, the major center for CPB, in Mashhad, Iran were randomly assigned to receive preoperative and intraoperative MP (30 mg/kg, 4 hours before bypass and in bypass prime, number 25) or preoperative MP only (30 mg/kg, number 25). Before and after bypass, four and 24 hours after bypass, serum IL-6 and IL-10 were measured by ELISA. In both groups, no significant difference with variation of expression for IL-6 (inflammatory factor) and IL-10 (anti-inflammatory factor) in different times after bypass was observed. No significant difference in reducing post bypass inflammation between preoperative steroid treatment and combined preoperative and intraoperative steroid administration reported and they had the same effects.

  19. Comparison of IL-6, IL-8 Concentrations in H. pylori- and non-H. pylori-associated Gastritis

    Directory of Open Access Journals (Sweden)

    Gontar Alamsyah Siregar

    2014-12-01

    Full Text Available BACKGROUND: Helicobacter pylori is a non-invasive microorganism causing intense gastric mucosal inflammatory and immune reaction. The gastric mucosal levels of the proinflammatory cytokines Interleukin 6 (IL-6 and IL-8 have been reported to be increased in H. pylori infection, but the serum levels in H. pylori infection is still controversial. The purpose of this study was to investigate the serum levels of IL-6 and IL-8 in H. pylori infection. METHODS: A cross sectional study was done on eighty consecutive gastritis patients admitted to endoscopy units at Adam Malik General Hospital and Permata Bunda Hospital, Medan, Indonesia from May-October 2014. Histopathology was performed for the diagnosis of gastritis. Rapid urease test for diagnosis of H. pylori infection. Serum samples were obtained to determine circulating IL-6 and IL-8. Univariate and bivariate analysis (independent t test were done. RESULTS: There were 41.25% patients infected with H. pylori. Circulatory IL-6 levels were significantly higher in H. pylori-infected patients compared to H. pylori negative, but there were no differences between serum levels of IL-8 in H. pylori positive and negative patients. CONCLUSIONS: The immune response to H. pylori promotes systemic inflammation, which was reflected in an increased level of serum IL-6. Serum levels of IL-8 were not significantly different between H. pylori positive and negative. KEYWORDS: Helicobacter pylori, gastritis, IL-6, IL-8, cytokine.

  20. IgG4-related disease involving polyserous effusions with elevated serum interleukin-6 levels: a case report and literature review.

    Science.gov (United States)

    Tong, Xiang; Bai, Min; Wang, Weiya; Han, Qingbing; Tian, Panwen; Fan, Hong

    2017-08-01

    Immunoglobulin G4-related disease (IgG4-RD) is a recently described immune-mediated fibroinflammatory disease with a characteristic histopathologic appearance that can affect various organs. We report a 43-year-old Chinese female patient with IgG4-RD involving polyserous effusions with reports of worsening exertional dyspnea for 3 months. Laboratory blood tests revealed that serum interleukin (IL)-6, carbohydrate antigens (CA-199 and CA-125), and alpha-fetoprotein levels were significantly increased, but serum IgG4 levels were normal. Repeat pleural effusion and ascite analysis showed lymphocyte-predominant exudates. In addition, computed tomography scan showed massive pleural effusion in the right pleural cavity, abdominal effusion, and some pericardial effusion with a partial compression atelectasis. Further, medical thoracoscopy was performed to examine the pleural cavity and found multiple nodules on the pleura and partly thickened pleura with a reddish color. Histopathologic and immunohistochemical examination revealed marked lymphocytes and IgG4-positive plasma cell infiltration. The patient was finally diagnosed with IgG4-RD according to the comprehensive diagnostic criteria, although the patient presented similar serological and pathological manifestations of Castleman disease (CD). Our case suggests that IgG4-RD may be one of the causes of polyserous effusions and shows the difficulties in differentiating between IgG4-RD and CD.

  1. PROCALCITONIN AND INTERLEUKIN-6 AS MARKERS OF SEVERE INFECTION IN CHILDREN WITH FEBRILE NEUTROPENIA

    Directory of Open Access Journals (Sweden)

    Lidija Kitanovski

    2004-12-01

    Full Text Available Background. The results of the study conducted to determine whether procalcitonin (PCT and interleukin-6 (IL-6 are more sensitive and specific markers of severe infection in children with febrile neutropenia (FN than routinelly used C-reactive protein (CRP are presented in the article. 68 episodes of FN experienced by 32 patients were divided into three groups according to the site of infection. Group 1: episodes of bacteraemia and/or clinical sepsis (n = 16, group 2: episodes of focal infection (n = 16 and group 3: episodes of fever of unknown origin (FUO (n = 36. Blood samples for further PCT and IL-6 determination were collected on three consecutive days. CRP concentrations were measured daily in each patient until the resolution of fever. PCT, IL-6 and CRP concentrations were measured on one occassion in each of the 18 afebrile patients with malignant disase forming the reference group. Serum PCT and IL-6 concentrations were measured by immunochemiluminometric and immunoenzymatic assay. Receiver Operating Characteristic (ROC curves were used to determine optimum sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of the studied parameters.Conclusions. PCT and IL-6 were found to be earlier and more sensitive markers of severe infection in neutropenic patients than CRP. The erliest one was IL-6, followed by PCT and CRP. Sequential determination of PCT up to 72 hours improved its diagnostic value, which was not the case for IL-6.In patients with gramnegative bacteraemias PCT concentracions were 3–5 times higher comparing to grampositive, whereas IL-6 concentrations were comparable in both groups.

  2. 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 ...

  3. Raised IL-6 Levels

    African Journals Online (AJOL)

    user

    Cardiovascular Associated Complications in HIV. Positive Zambians before ... compare plasma levels of IL-6 in HIV positive and. HIV negative .... cancer. Results from this study showed that IL-6 levels in. HIV positive ART naive individuals were significantly higher than in the HIV positive individuals on ART. Our findings ...

  4. Clinical Phenotype of Depression Affects Interleukin-6 Synthesis.

    Science.gov (United States)

    Zadka, Łukasz; Dzięgiel, Piotr; Kulus, Michał; Olajossy, Marcin

    2017-06-01

    Major depressive disorder (MDD) is not a single disease, but a number of various ailments that form one entity. Psychomotor retardation, anhedonia, sleep disorders, an increased suicide risk, and anxiety are the main symptoms that often define the clinical diagnosis of depression. Interleukin-6 (IL-6), as one of the proinflammatory cytokines, seems to be overexpressed during certain mental disorders, including MDD. Overexpression of IL-6 in depression is thought to be a factor associated with bad prognosis and worse disease course. IL-6 may directly affect brain functioning and production of neurotransmitters; moreover, its concentration is correlated with certain clinical symptoms within the wide range of depressive symptomatology. Furthermore, there is a strong correlation between IL-6 synthesis and psychosomatic functioning of the patient. This article discusses potential sources and significance of IL-6 in the pathogenesis of depression.

  5. Effect of blocking TNF on IL-6 levels and metastasis in a B16-BL6 melanoma/mouse model.

    Science.gov (United States)

    Cubillos, S; Scallon, B; Feldmann, M; Taylor, P

    1997-01-01

    We studied the relationship between tumour necrosis factor (TNF) and interleukin 6 (IL-6) levels, and the metastatic process in C57BL/6 mice after intravenous inoculation of B16-BL6 melanoma cells. Bioactive TNF was not detectable in the sera of inoculated mice, but these animals did show higher TNF levels following intraperitoneal challenge with lipopolysaccharide (LPS) compared to control animals. Serum IL-6 levels were increased in inoculated animals. Injection of a hybrid molecule (p55-sf2) composed of the human p55 TNF receptor extracellular domain coupled to a human constant region backbone, decreased serum TNF (after LPS challenge) and IL-6 levels in inoculated animals. Lung metastases at 7-14 days were reduced, compared to human IgG-injected control animals, but this effect was lost at day 21 postinoculation. The results suggest that the reduction in the number of metastases may be related to the effect of blocking TNF activity.

  6. 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.

  7. 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.

  8. Evaluation of interleukin-6 and serotonin as biomarkers to predict response to fluoxetine.

    Science.gov (United States)

    Manoharan, Aarthi; Rajkumar, Ravi Philip; Shewade, Deepak Gopal; Sundaram, Rajan; Muthuramalingam, Avin; Paul, Abialbon

    2016-05-01

    Only 30% of major depressive disorder (MDD) patients achieve complete remission with a serotonergic antidepressant (selective serotonin reuptake inhibitor). We investigated the potential of serotonin (5-HT) and interleukin-6 (IL-6) to serve as functional biomarkers of fluoxetine response. Serum IL-6 and 5-HT were measured in 73 MDD patients (39 responders and 34 non-responders) pre- and 6 weeks post-treatment and in 44 normal controls with ELISA. Fluoxetine and norfluoxetine were measured using LC MS/MS. IL-6 levels were significantly higher in MDD patients when compared with controls (p Fluoxetine and norfluoxetine concentrations were not significantly different in responders and non-responders, and there was no correlation between fluoxetine concentrations and percentage reduction in 5-HT from week 0 to 6. 5-HT and IL-6 may not serve as useful markers of response to fluoxetine because of inconsistent results across different studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. 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

  10. 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.

  11. Evaluation of C-reactive protein and interleukin-6 in the peripheral blood of patients with chronic periodontitis.

    Science.gov (United States)

    Gani, Dhruva Kumar; Lakshmi, Deepa; Krishnan, Rama; Emmadi, Pamela

    2009-05-01

    The aim of the present study was to investigate systemic levels of inflammatory markers of cardiovascular diseases like C-reactive protein and interleukin-6 in patients with chronic periodontitis, in comparison to periodontally healthy individuals. A total of 42 individuals, both males and females above the age of 30 years, were included in the study. Healthy controls (Group I, n = 14), chronic localized periodontitis (Group II, n = 14), and chronic generalized periodontitis (Group III, n = 14), all without any medical disorder, were recruited. Peripheral blood samples were taken and C-reactive protein (CRP) levels were estimated in the serum samples by using the Particle-Enhanced Turbidimetric Immunoassay (PETIA) technique. Serum samples of Interleukin-6 (IL-6) were assayed by using the Chemiluminescent Immunoassay (IMMULITE) technique. When mean CRP levels were compared between the groups, group III showed statistical significance when compared to group I (P = 0.04). Group III had a higher median IL-6 level (6.35 pg/mL) than Group II (Periodontitis results in higher systemic levels of CRP and IL-6. These elevated inflammatory factors may increase inflammatory activity in atherosclerotic lesions and potentially increasing the risk for cardiovascular events.

  12. Interleukin-6 overexpression induces pulmonary hypertension.

    Science.gov (United States)

    Steiner, M Kathryn; Syrkina, Olga L; Kolliputi, Narasaish; Mark, Eugene J; Hales, Charles A; Waxman, Aaron B

    2009-01-30

    Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.

  13. Adjunctive N-acetylcysteine in depression: exploration of interleukin-6, C-reactive protein and brain-derived neurotrophic factor.

    Science.gov (United States)

    Hasebe, Kyoko; Gray, Laura; Bortolasci, Chiara; Panizzutti, Bruna; Mohebbi, Mohammadreza; Kidnapillai, Srisaiyini; Spolding, Briana; Walder, Ken; Berk, Michael; Malhi, Gin; Dodd, Seetal; Dean, Olivia M

    2017-12-01

    This study aimed to explore effects of adjunctive N-acetylcysteine (NAC) treatment on inflammatory and neurogenesis markers in unipolar depression. We embarked on a 12-week clinical trial of NAC (2000 mg/day compared with placebo) as an adjunctive treatment for unipolar depression. A follow-up visit was conducted 4 weeks following the completion of treatment. We collected serum samples at baseline and the end of the treatment phase (week 12) to determine changes in interleukin-6 (IL6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following NAC treatment. NAC treatment significantly improved depressive symptoms on the Montgomery-Asberg Depression Rating Scale (MADRS) over 16 weeks of the trial. Serum levels of IL6 were associated with reductions of MADRS scores independent of treatment response. However, we found no significant changes in IL6, CRP and BDNF levels following NAC treatment. Overall, this suggests that our results failed to support the hypothesis that IL6, CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression. IL6 may be a useful marker for future exploration of treatment response.

  14. Interleukin-6 modifies mRNA expression in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Hassing, Helle Adser; Wojtaszewski, Jørgen; Jakobsen, Anne Hviid

    2011-01-01

    Aim: The aim of the present study was to test the hypothesis that interleukin-6 plays a role in exercise-induced PGC-1a and TNFa mRNA responses in skeletal muscle and to examine the potential IL-6 mediated AMPK regulation in these responses. Methods: Whole body IL-6 knockout and wildtype (WT) mal...

  15. 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

  16. 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

    Full Text Available Davood Attaran1, Shahrzad M Lari1, Mohammad Towhidi1, Hassan Ghobadi Marallu2, Hossein Ayatollahi1, Mohammad Khajehdaluee1, Mostafa Ghanei3, Reza Basiri11Lung Disease and Tuberculosis Research Center, Mashhad University of Medical Science, 2Ardabil University of Medical Sciences, 3Research Center of Chemical Injuries, Baqiyatallah University of Medical Sciences, Tehran, IranObjectives: Chronic obstructive pulmonary disease (COPD is one of the main late complications of sulfur mustard poisoning. The aim of this study was to evaluate serum levels of interleukin (IL-6 in war veterans with pulmonary complications of sulfur mustard poisoning and their correlation with severity of airways disease.Methods: Fifty consecutive patients with sulfur mustard poisoning and stable COPD, and of mean age 46.3 ± 9.18 years were enrolled in this study. Thirty healthy men were selected as controls and matched to cases by age and body mass index. Spirometry, arterial blood gas, six-minute walk test, BODE (body mass index, obstruction, dyspnea, and exercise capacity, and St George’s Respiratory Questionnaire about quality of life were evaluated. Serum IL-6 was measured in both patient and control groups.Results: Fifty-four percent of patients had moderate COPD. Mean serum IL-6 levels were 15.01 ± standard deviation (SD 0.61 pg/dL and 4.59 ± 3.40 pg/dL in the case and control groups, respectively (P = 0.03. There was a significant correlation between IL-6 levels and Global Initiative for Chronic Obstructive Lung Disease stage (r = 0.25, P = 0.04 and between IL-6 and BODE index (r = 0.38, P = 0.01. There was also a significant negative correlation between serum IL-6 and forced expiratory volume in one second (FEV1, r = -0.36, P = 0.016.Conclusion: Our findings suggest that serum IL-6 is increased in patients with sulfur mustard poisoning and COPD, and may have a direct association with airflow limitation.Keywords: sulfur mustard, chronic obstructive pulmonary

  17. The preparation of recombinant interleukin-6 and its protection for irradiated guinea-pigs

    International Nuclear Information System (INIS)

    Wang Junfu; Zhang Jie; Zhang Jianhua; Feng Jinbo; Xu Jie; Wang Baohong

    2002-01-01

    Objective: To purify recombinant human interleukin-6 from gene-engineered E. coli and study the effects of IL-6 on survival period and platelet count of irradiated guinea-pigs. Methods: Recombinant human IL-6 was expressed in gene-engineered E. coli and purified with reversed phase chromatography. Purified IL-6 was then administered to irradiated guinea-pig. Results: IL-6 could significantly prolong the survival period and increase the platelet count of irradiated guinea-pigs. Conclusion: IL-6 showed its effective protection for irradiated guinea-pigs

  18. Tumour Necrosis Factor-Α, Interleukin-1 and Interleukin-6 Serum Levels and Its Correlation with Pain Severity in Chronic Tension-Type Headache Patients: Analysing Effect of Dexketoprofen Administration.

    Science.gov (United States)

    Rambe, Aldy Safruddin; Sjahrir, Hasan; Machfoed, Moh Hasan

    2017-03-15

    The purpose of this study is to see the effect of Dexketoprofen on TNF-α, IL-1, and IL-6 serum levels in Chronic Tension-Type Headache (CTTH) patients and its correlation with pain severity. The study subjects were recruited consecutively from the study population. Venous blood was taken at baseline to measure serum levels of TNF-α, IL-1, and IL-6 and after ten consecutive days of Dexketoprofen 25 mg once daily. Twenty three subjects participated in this study, 3 male (13.0%) and 20 female (87%). A significant difference between NRS score at baseline and after treatment (4.86 ± 1.82 vs. 1.96 ± 1.40, p = 0.001) was found. No significant difference found between baseline and after treatment TNF-α (1.48 ± 0.65 pg/dl vs. 1.48 ± 0.63 pg/dl, p = 0.963), IL-1 (0.16 ± 0.80 pg/dl vs. 0.26 ± 0.31 pg/dl, p = 0.168) nor IL-6 serum levels (1.06 ± 0.83 pg/dl vs. 1.04 ± 0.81 pg/dl, p = 0.915). A weak negative (R = -0.266) non significant correlation (p = 0.219) was found between NRS score and TNF-α. A positive weak negative (R = 0.221) non significant correlation (p = 0.311) between NRS score and IL-1. NRS score and IL-6 had a negative very weak (R = -0.019) non significant negative correlation (p = 0.931). Dexketoprofen decreased pain intensity significantly (p = 0.001), but had no effect on TNF-α IL-1 nor IL-6 serum levels. NRS score had a weak and non significant negative correlation with TNF-α, a weak and non significant positive correlation with IL-1, and a very weak and non significant negative correlation with IL-6 serum levels.

  19. Tumour Necrosis Factor-Α, Interleukin-1 and Interleukin-6 Serum Levels and Its Correlation with Pain Severity in Chronic Tension-Type Headache Patients: Analysing Effect of Dexketoprofen Administration

    Directory of Open Access Journals (Sweden)

    Aldy Safruddin Rambe

    2017-02-01

    Full Text Available AIM: The purpose of this study is to see the effect of Dexketoprofen on TNF-α, IL-1, and IL-6 serum levels in Chronic Tension-Type Headache (CTTH patients and its correlation with pain severity. METHOD: The study subjects were recruited consecutively from the study population. Venous blood was taken at baseline to measure serum levels of TNF-α, IL-1, and IL-6 and after ten consecutive days of Dexketoprofen 25 mg once daily. RESULTS: Twenty three subjects participated in this study, 3 male (13.0% and 20 female (87%. A significant difference between NRS score at baseline and after treatment (4.86 ± 1.82 vs. 1.96 ± 1.40, p = 0.001 was found. No significant difference found between baseline and after treatment TNF-α (1.48 ± 0.65 pg/dl vs. 1.48 ± 0.63 pg/dl, p = 0.963, IL-1 (0.16 ± 0.80 pg/dl vs. 0.26 ± 0.31 pg/dl, p = 0.168 nor IL-6 serum levels (1.06 ± 0.83 pg/dl vs. 1.04 ± 0.81 pg/dl, p = 0.915. A weak negative (R = -0.266 non significant correlation (p = 0.219 was found between NRS score and TNF-α. A positive weak negative (R = 0.221 non significant correlation (p = 0.311 between NRS score and IL-1. NRS score and IL-6 had a negative very weak (R = -0.019 non significant negative correlation (p = 0.931. CONCLUSIONS: Dexketoprofen decreased pain intensity significantly (p = 0.001, but had no effect on TNF-α IL-1 nor IL-6 serum levels. NRS score had a weak and non significant negative correlation with TNF-α, a weak and non significant positive correlation with IL-1, and a very weak and non significant negative correlation with IL-6 serum levels.

  20. Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women.

    Science.gov (United States)

    Bustamante, M; Nogués, X; Mellibovsky, L; Agueda, L; Jurado, S; Cáceres, E; Blanch, J; Carreras, R; Díez-Pérez, A; Grinberg, D; Balcells, S

    2007-11-01

    Osteoporosis and obesity are complex diseases with a strong genetic component. Bone mineral density (BMD) and body mass index (BMI) linkage studies identified a locus at 1q21-23, where the interleukin-6 receptor (IL6R) gene is located. The IL6R and the gp130 receptors are the mediators of IL6 action. Serum levels of IL6 and sIL6R (the soluble form of IL6R) are higher in several diseases such as osteoporosis or obesity. Variants at IL6R have been associated with BMI and obesity. However, IL6R is an as-yet-unexplored osteoporosis candidate gene. In the present study we analysed two polymorphisms in the IL6R promoter, -1435 C/T (rs3887104) and -208 G/A (rs4845617), and the Asp358Ala polymorphism (rs8192284), in relation to both BMD and BMI in a cohort of 559 postmenopausal Spanish women. The promoter polymorphisms, -1435 C/T and -208 G/A were associated with femoral neck (FN) BMD (P=0.011 and P=0.025 respectively). The C-A and T-G promoter haplotypes were also associated with FN BMD. Additionally, the Asp358Ala variant was associated with lumbar spine BMD (P=0.038). Finally, the -208 G/A polymorphism and the C-G and C-A haplotypes were associated with BMI and obesity, where GG was the risk genotype (P=0.033 for BMI; P=0.010 for obesity). These data suggest that variants in the IL6R gene are not only involved in the determination of BMI but also relevant for the determination of BMD. The IL6R gene may belong to the growing list of genes known to be involved in both phenotypes.

  1. Interleukin-6 Levels in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Zheng Peng

    Full Text Available The change of serum interleukin-6(IL-6 levels in women with polycystic ovary syndrome (PCOS, as well as the relations between IL-6 levels and body mass index (BMI, insulin resistance(IR and androgen status of PCOS patients, are not fully understood.A literature search was performed in October 2015 using PubMed, Embase and the Cochrane Library databases to identify studies. Random-effects model was used to estimate the standardized mean differences (SMDs with 95% confidence intervals (CIs.Twenty articles with 25 case-control studies included 1618 women (922 PCOS patients and 696 controls were included in this study. IL-6 levels in controls were significantly lower than that of PCOS patients (SMD = 0.78, 95%CI = 0.41-1.16, P<0.001, with significant heterogeneity across studies (I2 = 91% and P<0.001. Meta-regression analysis model indicated IR status was the main source of heterogeneity (P = 0.005. Results from group analysis suggested that high IL-6 levels in PCOS were significantly associated with Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR ratio and total testosterone ratio (T ratio, and was found in both lean and obese women with PCOS. Cumulative meta-analysis results indicated the total effect size (SMD had tend to be stable since 2012(0.79 to 0.92.A high IL-6 level is not an intrinsic characteristic of PCOS, but may be a useful monitoring biomarker for the treatment of PCOS.

  2. 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

  3. Concentration of MMP-9, TNF-a and IL-6 in patients with tumors and tumor-like bone lesions

    Directory of Open Access Journals (Sweden)

    Puchinyan D.M.

    2017-09-01

    Full Text Available Aim: to determine the concentration of MMP-9, TNF-a and IL-6 in blood serum of patients with benign and malignant bone tumors and feasibility of cytokine data use for differential diagnostics of the neoplastic process nature. Material and Methods. Levels of matrix metalloproteinase-9 (MMP-9, tumor necrosis factor-a (TNF-a and interleukin-6 (IL-6 in blood serum were determined by the immunoenzyme method in 64 patients with bone tissue neoplasms (fibrous dysplasia, osteocystoma, giant-cell tumor, osteosarcoma, chondrosarcoma, bone metastases, multiple myeloma. Re-sults. MMP-9 level was heightened in patients suffered from chondrosarcoma and multiple myeloma. TNF-a and IL-6 expression was increased in cases with bone metastases. MMP-9, TNF-a and IL-6 levels were higher in cases with malignant bone neoplasms than in cases with benign bone tumors. Conclusion. MMP-9, TNF-a and IL-6 participate in the neoplastic process pathogenesis directly. Nevertheless it is too early to speak about the diagnostic value of the cytokines in cases with tumorous bone affection.

  4. Interleukin 6 modulates acetylcholinesterase activity of brain neurons

    International Nuclear Information System (INIS)

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

    1995-01-01

    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)

  5. 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

  6. Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

    NARCIS (Netherlands)

    Cenit, M.C.; Simeon, C.P.; Vonk, M.C.; Callejas-Rubio, J.L.; Espinosa, G.; Carreira, P.; Blanco, F.J.; Narvaez, J.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Garcia, I.; Garcia-Hernandez, F.J.; Gallego, M.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; Garcia de la Pena, P.; Lopez-Longo, F.J.; Gonzalez-Gay, M.A.; The Spanish Scleroderma, G.; Hesselstrand, R.; Riemekasten, G.; Witte, T.J.M. de; Voskuyl, A.E.; Schuerwegh, A.J.; Madhok, R.; Fonseca, C.; Denton, C.; Nordin, A.; Palm, O.; Laar, J.M. van; Hunzelmann, N.; Distler, J.H.; Kreuter, A.; Herrick, A.; Worthington, J.; Koeleman, B.P.; Radstake, T.R.D.J.; Martin, J.

    2012-01-01

    OBJECTIVE: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and

  7. IL-6 gene polymorphisms and sepsis in icu adult romanian patients: a prospective study

    Directory of Open Access Journals (Sweden)

    Georgescu Anca Meda

    2017-03-01

    Full Text Available Objectives: The goal of the study was to investigate the correlations between the interleukin-6 IL-6 -174 G/C and IL-6 -572 G/C gene polymorphisms and sepsis risk and severity in adult ICU patients.

  8. Clinical significance of determination of the levels of serum IL-6, TNF-α and hs-CRP in patients with DM2 complicated with coronary heart disease (CHD)

    International Nuclear Information System (INIS)

    Li Juan; Zhao Qian; Zhang Dajun

    2007-01-01

    Objective: To investigate the significance of changes of serum IL-6, TNF-α, hs-CRP levels in development of coronary heart disease in patients with type 2 diabetes mellitus. Methods: Serum IL-6, TNF-α (with RIA). hs-CRP (with CLIA) and FPG, TG, cholesterol (with biochemistry) contents were measured in (1) DM2 patients complicated with CHD, n=40 and (2) DlVI2 patients without CHD, n=48. Results: The BMI and FPG, TG levels were significantly higher in patients complicated with heart disease than those in patients without CHD (P<0.05) with the exception of cholesterol. The levels of IL-6, TNF-α and hs-CRP were also significantly higher in patients with heart disease than those in patients without heart disease (P<0.05). Conclusion: The high levels of IL-6, TNF-α and hs-CRP played important role in the development of coronary heart disease. Monitoring those levels might be helpful in assessment of treatment efficacy and outcome prediction. (authors)

  9. Resistin, interleukin-6, tumor necrosis factor-alpha, and human semen parameters in the presence of leukocytospermia, smoking habit, and varicocele.

    Science.gov (United States)

    Moretti, Elena; Collodel, Giulia; Mazzi, Lucia; Campagna, MariaStella; Iacoponi, Francesca; Figura, Natale

    2014-08-01

    To explore the relationships between resistin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and semen parameters, sperm apoptosis, and necrosis in infertile patients and in control subjects with unknown reproductive potential with/without smoking habits, leukocytospermia, and varicocele. Prospective study. Sperm laboratory. A total of 110 selected men. Family history, clinical/physical examination, ELISA determination (resistin, IL-6, TNF-α), semen analysis, annexin V/propidium iodide assay. Relationships among resistin, IL-6, and TNF-α and semen parameters in the presence of smoking habits, varicocele, leukocytospermia, and in infertile subjects. Resistin level was higher in semen than in serum. Resistin semen levels showed negative correlations with sperm motility and positive correlations with apoptotic, necrotic sperm and TNF-α and IL-6 levels. Resistin, TNF-α, and IL-6 levels were higher in smokers compared with nonsmokers and in cases with leukocytospermia, in which an increase in necrotic sperm and a decrease in the number of sperm with normal morphology and motility were observed. Cytokine levels were significantly higher in infertile patients compared with control subjects with unknown reproductive potential. A total of 74.5% of infertile patients showed leukocytospermia. Semen resistin correlated with IL-6, TNF-α, and sperm quality; in cases of leukocytospermia and smoking habits, resistin concentrations were increased, suggesting that resistin may play a regulatory role in inflammation of the male reproductive system. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Study on the serum levels of relevant cytokines IL-β, IL-6, IL-8 and tumor markers CEA, CA15-3, PRL in breast cancer patients with bone metastatic lesions shown on SPECT radio-nuclide bone scan

    International Nuclear Information System (INIS)

    Zhu Bao

    2009-01-01

    Objective: To explore the correlationship between SPECT radionuclide bone scan and serum levels of three tumor markers as well as three cytokines in patients with breast cancer. Methods: Serum levels of IL-1β, IL-6, IL-8, CEA, CA15-3(with RIA) and PRL(with CLIA) were determined in 1)20 breast cancer patients with definite bone metastatic lesions shown on radio-nuclide bone scan 2) 20 breast cancer patients without bone metastasis 3) 30 patients with benign breast disorders and 4) 35 controls. Results: The serum tumor markers levels in patients osseous metastasis were significantly higher than those in the other three groups (P 0.05). The serum levels of IL-6, IL-8, IL-1β in patients with osseous metastasis were also significantly higher than those in other groups(P<0.05). Conclusion: Over expression of CEA, CA15-3 and PRL as well as IL-6, IL-8, IL-1β were related with osseous metastasis from breast cancer. Determination of the levels of these six parameters would be helpful for dynamic monitoring of the extent of metastasis. (authors)

  11. Improvement of reduced serum cartilage oligomeric matrix protein levels in systemic juvenile idiopathic arthritis patients treated with the anti-interleukin-6 receptor monoclonal antibody tocilizumab.

    Science.gov (United States)

    Nakajima, Shoko; Naruto, Takuya; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Nishimaki, Shigeru; Yokota, Shumpei

    2009-01-01

    In this study, we determined serum cartilage oligomeric matrix protein (COMP) levels in systemic juvenile idiopathic arthritis (sJIA) patients during both the active and the remission phases to investigate how the growth cartilage turnover changed under tocilizumab treatment. Specimens were collected from 201 healthy children under 16 years of age with no growth impairment, and paired sera were collected from 11 sJIA patients treated with tocilizumab. Disease activity was assessed from white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and ferritin, and the COMP concentration was determined by sandwich enzyme-linked immunosorbent assay. Serum COMP concentrations were found independent of age, and the mean value in healthy children was 17.74+/-5.6 U/L. The mean serum COMP in sJIA patients during the active phase was 10.75+/-3.9 U/L, lower than that of healthy children. The mean serum COMP in the remission phase (14.89+/-3.9 U/L) was significantly higher than that in the active period (P<0.05). These results suggested that in sJIA patients, a reduced serum COMP concentration is a useful marker of active disease and growth impairment, and that the growth cartilage turnover suppressed during the active phase is improved in the remission phase under tocilizumab treatment.

  12. [Brd3 promotes IL-6 production via enhancing acetylase CBP recruitment and histone 3 acetylation within IL6 promoter].

    Science.gov (United States)

    Ren, Wenhui; Sun, Donghao; Wang, Chunmei; Li, Nan

    2016-10-01

    Objective To investigate the role of bromodomain containing 3 (Brd3) in LPS-triggered interleukin-6 (IL-6) production in macrophages and the underlying mechanism. Methods CRISPR-Cas9 technology was used to screen an RAW264.7 cell line with Brd3 knockout (Brd3 -/- ). The Brd3 -/- cells were used as an experimental group, and the parential cells expressing wide-type Brd3 as a control group. The IL-6 level in cell culture supernatant was detected by ELISA after 100 ng/mL LPS challenging. Effect of Brd3 knockout on the expression and activation of signal pathways involved in IL-6 expression, including the NF-κB and mitogen-activated protein kinase (MAPK) pathways were examined by Western blot analysis. Chromatin immunoprecipitation (ChIP) assay was used to evaluate the recruitment of acetylase CREB-binding protein (CBP) to IL6 gene promoter and the acetylation level of histone 3 within IL6 gene promoter. Results LPS treatment significantly downregulated Brd3 expression in mouse peritoneal macrophages. LPS-induced production of IL-6 was significantly inhibited in Brd3 -/- macrophages. The expressions and activation of signal molecules within NF-κB and MAPK pathways were barely affected. Brd3 knockout significantly decreased the recruitment of acetylase CBP to IL6 gene promoter, and the acetylation level of histone3 within IL6 gene promoter was also repressed. Conclusion Brd3 promotes LPS-triggered IL-6 production via promoting the recruitment of CBP to IL6 promoter and enhancing the acetylation level of histone 3 within IL6 promoter.

  13. Higher proliferation of peritumoral endothelial cells to IL-6/sIL-6R than tumoral endothelial cells in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhuang, Peng-Yuan; Wang, Jian-Dong; Tang, Zhao-Hui; Zhou, Xue-Ping; Quan, Zhi-Wei; Liu, Ying-Bin; Shen, Jun

    2015-01-01

    This study aimed to explore the responses to the interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) complex in peritumoral endothelial cells (PECs) and tumor endothelial cells (TECs), as well as determine the signaling pathways in the angiogenesis of hepatocellular carcinoma (HCC). The expression of IL-6, IL-6R, gp130, CD68, HIF-1α, and microvessel density (MVD) were assessed with an orthotopic xenograft model in nude mice. ECs were incubated under hypoxic conditions to detect IL-6 and gp130. The proliferation of PECs and TECs in the presence of IL-6 and sIL-6R, as well as the expression of gp130, JAK2/STAT3, PI3K/AKT in endothelial cells were measured. Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth. Hypoxia could directly induce IL-6 expression, but not gp130 in PECs. The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT. PECs exhibited higher proliferation in response to IL-6/sIL-6R co-treatment compared with TECs in HCC via the up-regulation of gp130 /JAK2/STAT3. PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment. The online version of this article (doi:10.1186/s12885-015-1763-2) contains supplementary material, which is available to authorized users

  14. ROLE OF IL-6 IN EXPERIMENTAL ARTHRITIS CAUSED BY TRANSFER OF ARTHRITOGENIC ANTIBODIES

    Directory of Open Access Journals (Sweden)

    M. S. Drutskaya

    2016-01-01

    Full Text Available Interleukin-6 (IL-6 exerts important functions on immune regulation. In case of high expression, IL-6 may promote autoimmune disorders, e.g., arthritis. Systemic IL-6 blockers based on monoclonal antibodies against IL-6, or its specific receptor subunit, are already used in clinical settings, adding to a range of known biological drugs, such as, TNF blockers. Rheumatic disorders and their experimental therapy are reproducible in mice. This study revealed systemically increased levels of IL-6 in developing arthritis caused by transfer of pathogenic antibodies, as well as the effects of IL-6 neutralization by monoclonal antibodies against murine IL-6. Our results suggest a pathogenic role of the two cytokines, TNF and IL-6, in experimental arthritis induced by passive transfer of anti-collagen antibodies.

  15. 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   

  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 (IL6) as a predictor outcome in patients with ...

    African Journals Online (AJOL)

    Elham Ragab

    2012-05-15

    May 15, 2012 ... borne infection and the leading indication for a liver transplant. [1]. Treatment ... cular hemolysis with reduction in gall bladder emptying and motility [11 .... The Child-Turcotte-Pugh classification system was used to assess the ...

  18. Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor.

    Science.gov (United States)

    Straub, Rainer H; Lehle, Karin; Herfarth, Hans; Weber, Markus; Falk, Werner; Preuner, Jurgen; Scholmerich, Jurgen

    2002-03-01

    Serum levels of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) are low in chronic inflammatory diseases, although the reasons are unexplained. Furthermore, the behaviour of serum levels of these hormones during an acute inflammatory stressful disease state is not well known. In this study in patients with an acute inflammatory stressful disease state (13 patients undergoing cardiothoracic surgery) and patients with chronic inflammation (61 patients with inflammatory bowel diseases (IBD)) vs. 120 controls, we aimed to investigate adrenal hormone shifts looking at serum levels of DHEA in relation to other adrenal hormones. Furthermore, we tested the predictive role of serum tumour necrosis factor (TNF) and interleukin-6 (IL-6) for a change of serum levels of DHEA in relation to other adrenal hormones. The molar ratio of serum levels of DHEA/androstenedione (ASD) was increased in patients with an acute inflammatory stressful disease state and was decreased in patients with chronic inflammation. The molar ratio of serum levels of DHEAS/DHEA was reduced during an acute inflammatory stressful disease state and was increased in patients with chronic inflammation. A multiple linear regression analysis revealed that elevated serum levels of TNF were associated with a high ratio of serum levels of DHEA/ASD in all groups (for IL-6 in patients with an acute inflammatory stressful disease state only), and, similarly, elevated serum levels of TNF were associated with a high ratio of serum levels of DHEAS/DHEA only in IBD (for IL-6 only in healthy subjects). This study indicates that changes of serum levels of DHEA in relation to serum levels of other adrenal hormones are completely different in patients with an acute inflammatory stressful disease state compared with patients with chronic inflammation. The decrease of serum levels of DHEAS and DHEA is typical for chronic inflammation and TNF and IL-6 play a predictive role for these changes.

  19. 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.

  20. Interleukin-6-receptor polymorphisms rs12083537, rs2228145, and rs4329505 as predictors of response to tocilizumab in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Enevold, Christian; Baslund, Bo; Linde, Louise

    2014-01-01

    Tocilizumab (TCZ), a monoclonal antibody targeting the human interleukin-6-receptor (IL-6R), is indicated for the treatment of rheumatoid arthritis (RA). We examined whether three IL6R single-nucleotide polymorphisms rs12083537, rs2228145 (formerly rs8192284), and rs4329505 with previously report...

  1. 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....

  2. Contraction and AICAR stimulate IL-6 vesicle depletion from skeletal muscle fibers in vivo.

    Science.gov (United States)

    Lauritzen, Hans P M M; Brandauer, Josef; Schjerling, Peter; Koh, Ho-Jin; Treebak, Jonas T; Hirshman, Michael F; Galbo, Henrik; Goodyear, Laurie J

    2013-09-01

    Recent studies suggest that interleukin 6 (IL-6) is released from contracting skeletal muscles; however, the cellular origin, secretion kinetics, and signaling mechanisms regulating IL-6 secretion are unknown. To address these questions, we developed imaging methodology to study IL-6 in fixed mouse muscle fibers and in live animals in vivo. Using confocal imaging to visualize endogenous IL-6 protein in fixed muscle fibers, we found IL-6 in small vesicle structures distributed throughout the fibers under basal (resting) conditions. To determine the kinetics of IL-6 secretion, intact quadriceps muscles were transfected with enhanced green fluorescent protein (EGFP)-tagged IL-6 (IL-6-EGFP), and 5 days later anesthetized mice were imaged before and after muscle contractions in situ. Contractions decreased IL-6-EGFP-containing vesicles and protein by 62% (P contraction. However, contraction-mediated IL-6-EGFP reduction was normal in muscle-specific AMP-activated protein kinase (AMPK) α2-inactive transgenic mice. In contrast, the AMPK activator AICAR decreased IL-6-EGFP vesicles, an effect that was inhibited in the transgenic mice. In conclusion, resting skeletal muscles contain IL-6-positive vesicles that are expressed throughout myofibers. Contractions stimulate the rapid reduction of IL-6 in myofibers, occurring through an AMPKα2-independent mechanism. This novel imaging methodology clearly establishes IL-6 as a contraction-stimulated myokine and can be used to characterize the secretion kinetics of other putative myokines.

  3. Elevated Circulating IL-1β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome

    OpenAIRE

    Vitoratos, Nicolaos; Papadias, Constantinos; Economou, Emmanuel; Makrakis, Evangelos; Panoulis, Constantinos; Creatsas, George

    2006-01-01

    The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding...

  4. 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.

  5. Avoidance-related EEG asymmetry predicts circulating interleukin-6.

    Science.gov (United States)

    Shields, Grant S; Moons, Wesley G

    2016-03-01

    Recent research has linked avoidance-oriented motivational states to elevated pro-inflammatory cytokine levels. According to one of many theories regarding the association between avoidance and cytokine levels, because the evolutionarily basic avoidance system may be activated when an organism is threatened or overwhelmed, an associated inflammatory response may be adaptive for dealing with potential injury in such threatening situations. To examine this hypothesis, we tested whether the neural correlate of avoidance motivation associates with baseline levels of the circulating pro-inflammatory cytokine interleukin-6 (IL-6). Controlling for covariates, greater resting neural activity in the right frontal cortex relative to the left frontal cortex-the neural correlate of avoidance motivation-was associated with baseline IL-6. These results thus support the hypothesis that the avoidance motivational system may be closely linked to systemic inflammatory activity. (c) 2016 APA, all rights reserved).

  6. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase

    OpenAIRE

    Brown, Charles O.; Salem, Kelley; Wagner, Brett A.; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R.; Goel, Apollina

    2012-01-01

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plu...

  7. Interleukin 1B variant -1473G/C (rs1143623) influences triglyceride and interleukin 6 metabolism

    Science.gov (United States)

    Interleukin 1b (IL1B or IL-1ß), is a key modulator of the immune response which exerts its functions mainly via interleukin 6 (IL6) regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susc...

  8. 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...

  9. Interleukin-6 enhances human Ig production, but not as a terminal differentiation factor for B lymphocytes

    NARCIS (Netherlands)

    van Kooten, C.; van Oers, M. H.; Aarden, L. A.

    1990-01-01

    Most B-cell differentiation systems are complicated by the fact that they are both T-cell- and monocyte-dependent. Immobilized anti-CD3 antibodies induce monocyte-independent T-cell activation, allowing investigation of the role of interleukin-6 (IL6) in the process of B-cell differentiation. We

  10. 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

  11. 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...

  12. 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…

  13. Is interleukin-6 receptor blockade the Holy Grail for inflammatory diseases?

    DEFF Research Database (Denmark)

    Febbraio, M A; Rose-John, S; Pedersen, B K

    2010-01-01

    Interleukin-6 (IL-6) has been linked to a myriad of diseases associated with inflammation, including rheumatoid arthritis (RA), Crohn's disease, and several types of cancer. In 2009 the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), t...

  14. 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

  15. 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

  16. IL-6 signaling in diabetic nephropathy: From pathophysiology to therapeutic perspectives.

    Science.gov (United States)

    Feigerlová, Eva; Battaglia-Hsu, Shyue-Fang

    2017-10-01

    Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD). Interleukin-6 (IL-6) signaling participates in inflammation responses central to the progression of DN. Current evidence suggests that these IL-6 responses are mediated via gp130-STAT3 dependent mechanisms which, on one hand, trigger globally the transition from innate to adaptive immune response, and on the other hand act locally for tissue remodeling and immune cell infiltration. In diabetic conditions the role of IL-6 is not well elucidated. Both IL-6 classical signaling pathway via receptor IL-6R (IL-6R) and IL-6 trans-signaling pathway via soluble IL-6R (sIL-6R) were shown to participate in the pathogenesis and progression of DN, and IL-6 appears to influence renal cells also in an autocrine manner. To date, evidence is limited. The goal of this review is to provide an overview of our current understanding on the role of IL-6 signaling in DN and to delineate challenges for future research. Putative sequential events related to IL-6 secretion by different cell populations in diabetic conditions are outlined. Further, we discuss potential applications of anti-IL-6 therapy in the context of DN. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Polymorphic variations in IL-1β, IL-6 and IL-10 genes, their circulating serum levels and breast cancer risk in Indian women.

    Science.gov (United States)

    Pooja, Singh; Chaudhary, Preeti; Nayak, Lakshma V; Rajender, Singh; Saini, Karan Singh; Deol, Debashish; Kumar, Sandeep; Bid, Hemant Kumar; Konwar, Rituraj

    2012-10-01

    Cytokines are known as important regulators of the entire gamut of cancer from initiation, invasion and metastasis. This fact and plethora of gene polymorphism data prompted us to investigate cytokine gene polymorphisms in breast cancer (BC) patients. Selected polymorphisms in the IL-1β [-511 T>C (rs16944) and +3954 C>T (rs1143634)]; IL-6 [-174 G>C (rs1800795)]; IL-10 [-1082 A>G (rs1800896), -819 T>C (rs1800871) and -592 A>C (rs1800872)] genes were genotyped in 200 BC patients and 200 healthy volunteers in a case-control study using PCR-RFLP and direct DNA sequencing techniques. Peripheral cytokine levels were measured using ELISA. Allele and genotype data were analyzed for significance of differences between cases and controls using Chi-Square [χ(2)] test. Two sided P-values of less than 0.05 were considered to be statistically significant. Peripheral level of all three cytokines did not show any significant difference between cases and controls. Allele and genotype frequency of IL-1β [-511 T>C (rs16944)] did not show any difference between cases and controls. On the other hand mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] associated with increased risk of BC. This was also true for pre-menopausal cases and for mutant genotype in post-menopausal cases. Mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] appeared to be protective in nature such that controls had a higher frequency of both mutant alleles and genotypes. None of the three SNPs in IL-10 gene associated with risk of BC, except significant association of mutant allele and genotypes of -1082 A>G (rs1800896) polymorphism with postmenopausal BC. Mutant allele and genotype at IL-1β [+3954 C>T (rs1143634)] site associated with increased BC risk, while mutant allele and genotypes at IL-6 [-174 G>C (rs1800795)] polymorphism appeared to be protective. Also, there was significant association of mutant allele and genotypes of IL-10 [-1082 A>G (rs1800896)] with postmenopausal BC. None of

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

    International Nuclear Information System (INIS)

    Chen, Miao-Fen; Hsieh, Ching-Chuan; Chen, Wen-Cheng; Lai, Chia-Hsuan

    2012-01-01

    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. 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.

  20. 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...

  1. 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...... (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-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

  2. 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...... (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-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

  3. 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)

  4. Stimulation of interleukin-6 production of periodontal ligament cells by Porphyromonas endodontalis lipopolysaccharide.

    Science.gov (United States)

    Ogura, N; Shibata, Y; Kamino, Y; Matsuda, U; Hayakawa, M; Oikawa, T; Takiguchi, H; Izumi, H; Abiko, Y

    1994-12-01

    Interleukin-6 (IL-6), which is a multifunctional cytokine, has important roles in acute and chronic inflammation and may also be implicated in bone resorption. We examined the IL-6 production in periodontal ligament (PDL) cells which were treated with lipopolysaccharide (LPS) from several oral inflammatory pathogens. The LPS from Porphyromonas endodontalis, which was isolated from infected root canals and radicular cyst fluids, was more potent than the LPS from any other periodontal organisms examined. P. endodontalis LPS stimulated IL-6 release from PDL cells in a time- and dose-dependent manner. Northern blot hybridization analysis revealed that the IL-6 mRNA level in PDL cells was increased by P. endodontalis LPS. These results suggest that stimulation of the IL-6 release of PDL cells by P. endodontalis LPS may have a role in the progression of inflammation and alveolar bone resorption in periodontal and periapical diseases.

  5. Effect of 13q deletion on IL-6 production in patients with multiple myeloma: a hypothesis may hold true.

    Science.gov (United States)

    Neemat, Kassem; Rania, Khalifa; Tarek, Mohamed; Hamdy, Abdel Azim

    2014-01-01

    Numerous studies have shown a correlation between 13q deletion and poor prognosis in multiple myeloma (MM), but the mechanisms are not fully understood. Earlier studies suggest that this lesion involves large segments or the entire long arm involving the retinoblastoma (Rb) gene. In myeloma, Rb gene is believed to down regulate interleukin-6 (IL-6) which plays a central role in the pathogenesis of MM. Therefore, it has been hypothesized that loss of the Rb gene might be associated with very high expression of IL-6 and subsequent bad prognosis. Hence this study evaluates IL-6 production in MM patients with and without 13q deletions and assesses their response to conventional and new therapeutic regimens. Forty MM patients and 20 matched controls were included in this study. Interphase fluorescence in situ hybridization (FISH) analysis was performed using LSI 13q14-specific probe. Serum levels of IL-6 were determined by ELISA. All patients received conventional chemotherapy. Refractory patients received other therapeutic regimens of Thalidomide or Bortezomib. Significant increase (p < 0.001) of IL-6 production was recorded in patients with a 13q deletion compared to patients with normal chromosome 13q status. These patients were also refractory to conventional chemotherapy but showed striking response to Thalidomide or Bortezomib. This study suggests that 13q deletions are associated with increased production of IL-6 in MM and this could be a possible cause of the associated bad prognosis. In addition, the results also show the potential to improve responses in patients with refractory MM with the introduction of novel therapies.

  6. IL-6 has no acute effect on the regulation of urea synthesis in vivo in rats

    DEFF Research Database (Denmark)

    Thomsen, Karen; Aagaard, Niels Kristian; Grønbæk, Henning

    2011-01-01

    Clinical or experimentally induced, active inflammation up-regulates the in vivo capacity of urea synthesis (CUNS), which promotes nitrogen removal from the body and metabolic catabolism. We have shown that tumor necrosis factor a (TNF-a) up-regulates CUNS and increases interleukin 6 expression (IL......-6) within hours of administration. The described effect of TNF-a on nitrogen homeostasis may, therefore, depend on IL-6....

  7. 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 b...

  8. 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

  9. Interleukin 6 stimulates hepatic glucose release from prelabeled glycogen pools

    International Nuclear Information System (INIS)

    Ritchie, D.G.

    1990-01-01

    Cytokines, derived from a wide variety of cell types, are now believed to initiate many of the physiological responses accompanying the inflammatory phase that follows either Gram-negative septicemia or thermal injury. Because hypoglycemia (after endotoxic challenge) and hyperglycemia (after thermal injury) represent well-characterized responses to these injuries, we sought to determine whether hepatic glycogen metabolism could be altered by specific cytokines. Cultured adult rat hepatocytes were prelabeled with [ 14 C]glucose for 24 h, a procedure that resulted in the labeling of hepatic glycogen pools that subsequently could be depleted (with concomitant [ 14 C]glucose release) by either glucagon or norepinephrine. After the addition of a highly concentrated human monocyte-conditioned medium (MCM) or various cytokines to these prelabeled cells, [ 14 C]glucose release was stimulated by MCM and recombinant human interleukin 6 (IL-6) but was not stimulated by other cytokines tested. Furthermore, only antisera to IL-6 were capable of reducing the glucose-releasing factor activity found in MCM. These data therefore suggest a novel glucoregulatory role for IL-6

  10. Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6.

    Science.gov (United States)

    Cutolo, Maurizio; Straub, Rainer H; Foppiani, Luca; Prete, Camilla; Pulsatelli, Lia; Sulli, Alberto; Boiardi, Luigi; Macchioni, Pierluigi; Giusti, Massimo; Pizzorni, Carmen; Seriolo, Bruno; Salvarani, Carlo

    2002-04-01

    To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH

  11. 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....

  12. Sex and interleukin-6 are prognostic factors for autoimmune toxicity following treatment with anti-CTLA4 blockade.

    Science.gov (United States)

    Valpione, Sara; Pasquali, Sandro; Campana, Luca Giovanni; Piccin, Luisa; Mocellin, Simone; Pigozzo, Jacopo; Chiarion-Sileni, Vanna

    2018-04-11

    Ipilimumab is a licensed immunotherapy for metastatic melanoma patients and, in the US, as adjuvant treatment for high risk melanoma radically resected. The use of ipilimumab is associated with a typical but unpredictable pattern of side effects. The purpose of this study was to identify clinical features and blood biomarkers capable of predicting ipilimumab related toxicity. We performed a prospective study aimed at analyzing potential clinical and biological markers associated with immune-related toxicity in patients treated with ipilimumab (3 mg/kg, q3w). We enrolled 140 consecutive melanoma patients treated with ipilimumab for metastatic disease. The following prospectively collected data were utilized: patient characteristics, previous therapies, level of circulating biomarkers associated with tumour burden or immune-inflammation status (lactic dehydrogenase, C-reactive protein, β2-microglobulin, vascular endothelial growth factor, interleukin-2, interleukin-6, S-100, alkaline phosphatase, transaminases) and blood cells subsets (leukocyte and lymphocyte subpopulations). Logistic regression was used for multivariate analysis of data. Out of 140 patients, 36 (26%) experienced a severe adverse event, 33 (24%) discontinued treatment for severe toxicity. Among the immune-profile biomarkers analyzed, only interleukin-6 was associated with the risk of toxicity. Female patients had a further increase of immune-related adverse events. Low baseline interleukin-6 serum levels (OR = 2.84, 95% CI 1.34-6.03, P = 0.007) and sex female (OR = 1.5, 95% CI 1.06-2.16 P = 0.022) and were significant and independent risk factors for immune related adverse events. Baseline IL6 serum levels and female sex were significantly and independently associated with higher risk of severe toxicity and could be exploited in clinical practice to personalize toxicity surveillance in patients treated with ipilimumab.

  13. 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

  14. Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development

    Directory of Open Access Journals (Sweden)

    Mekayla A. Storer

    2018-05-01

    Full Text Available Summary: Circulating systemic factors can regulate adult neural stem cell (NSC biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6, since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools. : In this report, Storer and colleagues demonstrate that the circulating cytokine IL-6, which is elevated in humans in different pathological situations, can perturb neural stem cell biology after birth. They show that IL-6 signaling is essential for self-renewal and maintenance of post-natal and adult NSCs in the murine forebrain under normal homeostatic conditions. Keywords: interleukin-6, neural stem cell, adult neurogenesis, CNS cytokines, postnatal brain development, stem cell depletion, neural stem cell niche, circulating stem cell factors, olfactory bulb

  15. High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide.

    Science.gov (United States)

    Isung, J; Aeinehband, S; Mobarrez, F; Nordström, P; Runeson, B; Asberg, M; Piehl, F; Jokinen, J

    2014-10-21

    The dysregulation of inflammation has been associated with depression and, more recently, with suicidal behaviors. The reports regarding the relationship between interleukin-6 (IL-6) and suicide attempts are inconsistent. Personality traits such as impulsivity and aggression are considered endophenotypes and important factors that underlie suicidal behaviors. The aim of the current study was to assess whether plasma and cerebrospinal fluid (CSF) levels of IL-6 are associated with personality traits among suicide attempters. We assessed the relationships among personality traits, IL-6 and violent suicide attempts. The plasma and CSF levels of IL-6 were measured in suicide attempters (plasma=58, CSF=39) using antibody-based immunoassay systems. Personality domains were assessed using the Karolinska Scale of Personality (KSP). IL-6 levels in plasma and CSF were used to predict personality domains via regression models. Plasma IL-6 was significantly and positively correlated with extraversion as well as the KSP subscales impulsivity and monotony avoidance. CSF IL-6 was positively correlated with monotony avoidance. Violent suicide attempts tended to be associated with high plasma IL-6 levels. Plasma and CSF levels of IL-6 were not significantly associated with each other. These results indicate that impulsivity and the choice of a violent suicide attempt method might be related to higher levels of IL-6 in individuals who attempt suicide. The neuroinflammation hypothesis of suicidal behavior on the basis of elevated IL-6 levels might be partly explained by the positive association between IL-6 and impulsivity, which is a key element of the suicidal phenotype.

  16. Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting

    Directory of Open Access Journals (Sweden)

    Rongrong Zhang

    2015-01-01

    Full Text Available Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS. Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

  17. Interleukin-6, vascular endothelial growth factor and transforming growth factor beta 1 in canine steroid responsive meningitis-arteritis

    Directory of Open Access Journals (Sweden)

    Maiolini Arianna

    2013-02-01

    Full Text Available Abstract Background Steroid Responsive Meningitis-Arteritis (SRMA is a common cause of inflammation of the canine central nervous system (CNS. To investigate if transforming growth factor beta 1 (TGF-β1, interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF are involved in the production of excessive immunoglobulin A (IgA, the induction of acute phase proteins and in the development of a systemic necrotizing vasculitis, characteristic of SRMA, these three signalling proteins were evaluated. Results Cerebrospinal fluid (CSF and serum samples of dogs during the acute phase of SRMA (SRMA were tested for IL-6, VEGF and TGF- β1. Results were compared to those of dogs affected with SRMA during treatment (SRMA Th and during relapse (SRMA R, to dogs with other meningoencephalomyelitides (ME, with miscellaneous non-inflammatory diseases of the CNS (CNS-Mix, with idiopathic epilepsy (IE, with systemic inflammatory diseases (Syst. Infl. and with healthy dogs (Healthy. Concentrations of IL-6 and VEGF in CSF were significantly elevated in the SRMA group compared to the other disease categories (p 1 were increased in SRMA group, but statistically significant differences were found only in comparison with Healthy and CNS-Mix groups. No differences were detected in the serum concentrations of TGF-β1 between the different groups. In untreated SRMA patients, a positive correlation (rSpear = 0.3549; P = 0.0337 between concentrations of TGF-β1 and IgA concentration was found in CSF, while concentrations of IL-6 and VEGF in CSF positively correlated with the degree of pleocytosis (rSpear = 0.8323; P Spear = 0.5711; P = 0.0166, respectively. Conclusions Our results suggest that these three signalling proteins are biomarkers of disease activity in SRMA. VEGF might play an important role in the development of a systemic arteritis. TGF-β1 is considered to be involved in the excessive IgA production, while IL-6 in the pleocytosis

  18. 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.

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

    Science.gov (United States)

    2017-01-01

    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. PMID:29211023

  20. 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.

  1. The Roles of Interleukin-6 in the Pathogenesis of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Misato Hashizume

    2011-01-01

    Full Text Available Several clinical studies have demonstrated that the humanized anti-interleukin-6 (IL-6 receptor antibody tocilizumab (TCZ improves clinical symptoms and prevents progression of joint destruction in rheumatoid arthritis (RA. However, the precise mechanism by which IL-6 blockade leads to the improvement of RA is not well understood. IL-6 promotes synovitis by inducing neovascularization, infiltration of inflammatory cells, and synovial hyperplasia. IL-6 causes bone resorption by inducing osteoclast formation via the induction of RANKL in synovial cells, and cartilage degeneration by producing matrix metalloproteinases (MMPs in synovial cells and chondrocytes. Moreover, IL-6 is involved in autoimmunity by altering the balance between Th17 cells and Treg. IL-6 also acts on changing lipid concentrations in blood and on inducing the production of hepcidin which causes iron-deficient anemia. In conclusion, IL-6 is a major player in the pathogenesis of RA, and current evidence indicates that the blockade of IL-6 is a beneficial therapy for RA patients.

  2. Pulmonary hypertension in patients with advanced heart failure is associated with increased levels of interleukin-6.

    Science.gov (United States)

    Dolenc, Jure; Šebeštjen, Miran; Vrtovec, Bojan; Koželj, Mirta; Haddad, François

    2014-08-01

    Inflammatory, endothelial and neurohormonal biomarkers are involved in heart failure (HF) and pulmonary hypertension (PH) pathogenesis. To study these biomarkers in PH due to advanced HF. Thirty adults with HF were included. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hsCRP), endothelin-1 and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were measured in peripheral vein and pulmonary artery during right heart catheterisation. IL-6, TNF-α, hsCRP and NT-proBNP correlated with pulmonary pressures independent of ventricular function, HF etiology and vascular bed. IL-6 was independent predictor of systolic pulmonary artery pressure (sPAP). Inflammatory biomarkers correlate to PH severity. IL-6 predicts sPAP in advanced HF.

  3. [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.

  4. 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

  5. Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model

    NARCIS (Netherlands)

    Tsuchida, Anika I.; Beekhuizen, Michiel; Rutgers, Marijn; van Osch, Gerjo J.V.M.; Bekkers, Joris E.J.; Bot, Arjan G.J.; Geurts, Bernd; Dhert, Wouter J.A.; Saris, Daniël B.F.; Creemers, Laura B.

    2012-01-01

    Introduction This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.

  6. Interleukin-6 responses to water immersion therapy after acute exercise heat stress: a pilot investigation.

    Science.gov (United States)

    Lee, Elaine C; Watson, Greig; Casa, Douglas; Armstrong, Lawrence E; Kraemer, William; Vingren, Jakob L; Spiering, Barry A; Maresh, Carl M

    2012-01-01

    Cold-water immersion is the criterion standard for treatment of exertional heat illness. Cryotherapy and water immersion also have been explored as ergogenic or recovery aids. The kinetics of inflammatory markers, such as interleukin-6 (IL-6), during cold-water immersion have not been characterized. To characterize serum IL-6 responses to water immersion at 2 temperatures and, therefore, to initiate further research into the multidimensional benefits of immersion and the evidence-based selection of specific, optimal immersion conditions by athletic trainers. Controlled laboratory study. Human performance laboratory Patients or Other Participants: Eight college-aged men (age = 22 ± 3 years, height = 1.76 ± 0.08 m, mass = 77.14 ± 9.77 kg, body fat = 10% ± 3%, and maximal oxygen consumption = 50.48 ± 4.75 mL·kg(-1) min(-1)). Participants were assigned randomly to receive either cold (11.70°C ± 2.02°C, n = 4) or warm (23.50°C ± 1.00°C, n = 4) water-bath conditions after exercise in the heat (temperature = 37°C, relative humidity = 52%) for 90 minutes or until volitional cessation. Whole-body cooling rates were greater in the cold water-bath condition for the first 6 minutes of water immersion, but during the 90-minute, postexercise recovery, participants in the warm and cold water-bath conditions experienced similar overall whole-body cooling. Heart rate responses were similar for both groups. Participants in the cold water-bath condition experienced an overall slight increase (30.54% ± 77.37%) in IL-6 concentration, and participants in the warm water-bath condition experienced an overall decrease (-69.76% ± 15.23%). We have provided seed evidence that cold-water immersion is related to subtle IL-6 increases from postexercise values and that warmer water-bath temperatures might dampen this increase. Further research will elucidate any anti-inflammatory benefit associated with water-immersion treatment and possible multidimensional uses of cooling

  7. Circulating TNF-alpha and IL-6 concentrations and TNF-alpha -308 G>A polymorphism in children with premature adrenarche

    Directory of Open Access Journals (Sweden)

    Pauliina eUtriainen

    2010-11-01

    Full Text Available Premature adrenarche (PA, the early rise in adrenal androgen production leading to prepubertal signs of androgen action, has been connected with adverse metabolic features. The metabolic syndrome is characterized by low grade inflammation which in turn is associated with increases in circulating proinflammatory cytokines, like tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6. We tested the hypothesis that serum concentrations of TNF-α and IL-6 are increased in PA by studing 73 children with PA and 98 age- and gender-matched controls. Serum TNF-α and IL-6 concentrations were measured using a multiplex bead array. The subjects were genotyped for the TNF-α gene -308 G>A polymorphism (known to affect TNF-α gene transcription, and genotype-phenotype associations were studied. The mean serum TNF-α concentration was higher in the PA than control children (20.4 vs. 18.4 pg/ml, P=0.048, whereas there was no significant difference in the mean serum IL-6 concentrations between the study groups. The difference in TNF-α was not explained by excess body weight in the PA subjects as the difference remained significant after BMI-adjustment (P=0.038. In the PA group, TNF-α concentration was not associated with metabolic-endocrine features, but high IL-6 was associated with lower birth weight. There was no difference in the genotype distribution of the TNF-α gene -308 G>A polymorphism between the PA and control groups. In conclusion, PA was associated with increased serum TNF-α concentrations which, unexpectedly, were not connected with BMI or insulin resistance. The TNF-α gene -308 G>A polymorphism does not seem to be associated with the development of PA.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. In humans IL-6 is released from the brain during and after exercise and paralleled by enhanced IL-6 mRNA expression in the hippocampus of mice

    DEFF Research Database (Denmark)

    Rasmussen, Per; Vedel, J-C; Olesen, J

    2011-01-01

    Aim: Plasma interleukin-6 (IL-6) increases during exercise by release from active muscles and during prolonged exercise also from the brain. The IL-6 release from muscles continues into recovery and we tested whether the brain also releases IL-6 in recovery from prolonged exercise in humans....... Additionally, it was evaluated in mice whether brain release of IL-6 reflected enhanced IL-6 mRNA expression in the brain as modulated by brain glycogen levels. Methods: Nine healthy male subjects completed 4 h of ergometer rowing while the arterio-jugular venous difference (a-v diff) for IL-6 was determined....... The IL-6 mRNA and the glycogen content were determined in mouse hippocampus, cerebellum and cortex before and after 2 h treadmill running (N = 8). Results: At rest, the IL-6 a-v diff was negligible but decreased to -2.2 ± 1.9 pg ml(-1) at the end of exercise and remained low (-2.1 ± 2.1 pg ml(-1) ) 1 h...

  14. Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Harder-Lauridsen, N M; Krogh-Madsen, R; Holst, Jens Juul

    2014-01-01

    increase the insulin-mediated glucose uptake. Men with type 2 diabetes not treated with insulin [n = 9, age 54.9 ± 9.7 (mean ± SD) yr, body mass index 34.8 ± 6.1 kg/m(2), HbA1c 7.0 ± 1.0%] received continuous intravenous infusion with either recombinant human IL-6 (rhIL-6) or placebo. After 1 h......Elevated interleukin-6 (IL-6) levels are associated with type 2 diabetes, but its role in glucose metabolism is controversial. We investigated the effect of IL-6 on insulin-stimulated glucose metabolism in type 2 diabetes patients and hypothesized that an acute, moderate IL-6 elevation would...

  15. 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.

  16. 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

  17. Levels of interleukin-6 in tears before and after excimer laser treatment

    OpenAIRE

    Resan Mirko; Stanojević Ivan; Petković-Ćurčin Aleksandra; Pajić Bojan; Vojvodić Danilo

    2015-01-01

    Background/Aim. Immune response and consequent inflammatory process which originate on ocular surface after a trauma are mediated by cytokines. Photoablation of corneal stroma performed by excimer laser causes surgically induced trauma. Interleukin-6 (IL-6) is mostly known as a proinflammatory cytokine. However, it also has regenerative and anti-inflammatory effects. It is supposed that this cytokine is likely to play a significant role in the process of co...

  18. [Predictive value of interleukin 6 from the umbilical cord blood in early neonatal infection].

    Science.gov (United States)

    Cosićkić, Almira; Skokić, Fahrija

    2009-01-01

    We have analyzed diagnostic value of interleukin 6 (IL-6) from the umbilical cord blood in recognition of early neonatal infection (ENI) of newborns whose mothers have obstetrical risks. The study included 120 newborns with birth weight ENI), group B (clinical signs and hematological parameters of ENI) and group C (newborns without ENI). Median of IL-6 value in group A was 48.5 pg/ml with sensitivity, specificity and diagnostic value in recognition of ENI 78%, 81% and 80%. In group B median of IL-6 was 49 pg/ml with sensitivity, specificity and diagnostic value 65%, 80% and 77%. In group C median of IL-6 was 9.7 pg/ml. We noticed significant connection between value of IL-6 and mother's urinary tract infection; group A (p=0.023), group B (p = 0.007). Also there was a remarkable relationship between mother's colpitis and level of IL-6 in newborn with ENI in group A (p=0.011) and group B (p = 0.012). High levels of IL-6 in umbilical cord blood can help us in recognition of newborns that are endangered by infection and they are clearly connected with some of mother's obstetrical risks.

  19. Glucocorticoid up-regulation of high-affinity interleukin 6 receptors on human epithelial cells

    International Nuclear Information System (INIS)

    Snyers, L.; De Wit, L.; Content, J.

    1990-01-01

    Interleukin 6 (IL-6) is a potent pleiotropic cytokine, known, among others, to stimulate immunoglobulin production by B cells and to trigger acute-phase protein synthesis by hepatocytes. Similar to IL-1, it is produced by monocytes and macrophages following an inflammatory challenge. Analysis of IL-6 receptor (IL-6R) expression on different human cell lines indicates that dexamethasone could up-regulate the number of IL-6R on one epithelial cell line (UAC) and on two hepatoma cell lines (HepG2 and Hep3B). This effect was confirmed by Scatchard analysis of binding experiments, using [ 35 S]methionine and [ 35 S]cysteine metabolically labeled IL-6. It was confirmed at the level of mRNA expression by Northern blot analysis. These results provide evidence for a link between IL-6 and glucocorticoids. They could represent an example of a system in which one role of glucocorticoids is to define more accurately the target of cytokines, and they could explain, at least partly, the frequently observed synergy between IL-6 and glucocorticoids, notably in the case of hepatocytes

  20. Interleukin 6 regulates metallothionein gene expression and zinc metabolism in hepatocyte monolayer cultures

    International Nuclear Information System (INIS)

    Schroeder, J.J.; Cousins, R.J.

    1990-01-01

    Attention has focused on the cytokine interleukin 6 (IL-6) as a major mediator of acute-phase protein synthesis in hepatocytes in response to infection and tissue injury. The authors have evaluated the effects of IL-6 and IL-1α as well as extracellular zinc and glucocorticoid hormone on metal-lothionein gene expression and cellular zinc accumulation in rat hepatocyte monolayer cultures. Further, they have evaluated the teleological basis for cytokine mediation by examining cyto-protection from CCl 4 -induced damage. Incubation of hepatocytes with IL-6 led to concentration-dependent and time-dependent increases in metallothionein-1 and -2 mRNA and metallothionein protein. The level of each was increased within 3 hr after the addition of IL-6 at 10 ng/ml. Maximal increases the metallothionein mRNA and metallothionein protein were achieved after 12 hr and 36 hr, respectively. Concomitant with the up-regulation of metallothionein gene expression, IL-6 also increased cellular zinc. Responses to IL-6 required the synthetic glucocorticoid hormone dexamethasone and were optimized by increased extracellular zinc. Thus, IL-6 is a major cytokine mediator of metallothionein gene expression and zinc metabolism in hepatocytes and provides cytoprotection from CCl 4 -induced hepatotoxicity via a mode consistent with dependence upon increased cellular metallothionein synthesis and zinc accumulation

  1. 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

  2. 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 ...

  3. There are no differences in IL-6, CRP and homocystein concentrations between women whose mothers had AD and women whose mothers did not have AD.

    Science.gov (United States)

    Devčić, Sanja; Glamuzina, Ljubomir; Ruljancic, Nedjeljka; Mihanovic, Mate

    2014-12-30

    A wide range of recent studies have detected inflammation as one of the most influent factors in the appearance and spreading of neurodegenerative brain diseases. We aimed to understand the influence of Interleukin-6 (IL-6), C-reactive protein (CRP) and homocysteine (Hcy) on patients suffering from Alzheimer׳s disease (AD) and on their descendants. Three groups of subjects were analyzed: 55 patients suffering from AD, 51 middle-aged daughters of the patients of the first group, and 53 subjects without positive family history of AD. The results of the conducted research are in accordance with the present scientific knowledge, namely a statistically significant difference for examined parameters has been determined between women suffering from AD and their daughters and control group examinees. No difference was found in serum concentrations of IL-6, highly sensitive C-reactive protein (hsCRP) and Hcy between the groups of the middle-aged descendants of patients with AD and healthy controls without family history of AD. This finding supports the hypothesis that these markers may not play causal role in the development of AD. This is supported by the obtained positive correlation between IL-6 and hsCRP and IL-6 and Hcy in AD patients while there is no such correlation between female subjects with or without a family history of AD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Α, Il-1β, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model.

    Science.gov (United States)

    Oztas, Berrin; Sahin, Deniz; Kir, Hale; Eraldemir, Fatma Ceyla; Musul, Mert; Kuskay, Sevinç; Ates, Nurbay

    2017-02-01

    The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups-Group 1: Saline, Group 2: Saline+PTZ (65mg/kg), Group 3: leptin (4mg/kg)+PTZ, Group 4: ghrelin (80μg/kg)+PTZ, and Group 5: NPY (60μg/kg)+PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained. Seizure activity was scored by observing seizure behavior, and the onset time, latency, and seizure duration were determined according to the EEG records. At the end of the experiments, blood samples were obtained in all groups to assess the serum TNF-α, IL-1β, IL-6, FGF-2, galanin, nitric oxide (NOֹ), malondialdehyde (MDA), and glutathione (GSH) levels. The electrophysiological and biochemical findings (p<0.05) of this study show that all three peptides have anticonvulsant effects in the pentylenetetrazol (PTZ)-induced generalized tonic-clonic convulsive seizure model. The reduction of the levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 caused by leptin, ghrelin, and NPY shows that these peptides may have anti-inflammatory effects in epileptic seizures. Also, leptin significantly increases the serum levels of the endogenous anticonvulsive agent galanin. The fact that each one of these endogenous peptides reduces the levels of MDA and increases the serum levels of GSH leads to the belief that they may have protective effects against oxidative damage that is thought to play a role in the pathogenesis of epilepsy. Our study contributes to the clarification of the role of these peptides in the brain in seizure-induced oxidative stress and immune system physiology and also presents new approaches to the etiology and treatment of tendency to epileptic seizures. Copyright

  5. 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

  6. 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.

  7. Interleukin 1β, tumor necrosis factor-α and interleukin 6 decreas nuclear thyroid hormone receptor capacity in a liver cell line

    International Nuclear Information System (INIS)

    Wolf, M.; Hansen, N.; Greten, H.

    1994-01-01

    Many of the acute inflammatory responses in critical illness are mediated by tumor necrosis factor-α (TNTF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). Furthermore, these cytokines are involved in mediating the characteristic changes of thyroid function during acute disease known as non-thyroidal illness. In the present studies the authors investigated in vitro whether TNF-α, IL-1β and IL-6 modify nuclear thyroid hormone receptor (TR) capacity and/or affinity. Regulation of TR synthesis was studied in the human hepatoma cell line Hep-G2. Subconfluent cells were incubated with recombinant cytokines in serum-free medium. Nuclear extracts were prepared by high-salt extraction of cell nuclei. Binding assays were performed with [ 125 I]-triiodothyronine; bound and free hormone were separated by filtration. Interleukin 1β decreased TR capacity in a dose-dependent manner. Compared with unstimulated cells, the TR capacity was reduced to 87.9 ± 3.9% after incubation with 0.1, 1.0 and 100 μg/l IL-1β, respectively. Interleukin 6 and TNF-α significantly reduced receptor capacity only at concentrations of 10μg/l or higher and the magnitude of the reduction was lower than with IL-1β. The TR capacity was reduced to 81.2 ± 2.3% and 83.2 ± 6.6% after stimulation with 10μg/l IL-6 or TNF-α, respectively. TR affinity was not altered significantly after stimulation with any of the cytokines. 44 refs., 4 figs

  8. IL-6 and IGF-1 signaling within and between muscle and bone: how important is the mTOR pathway for bone metabolism?

    NARCIS (Netherlands)

    Bakker, A.D.; Jaspers, R.T.

    2015-01-01

    Insulin-like growth factor 1 (IGF-1) and interleukin 6 (IL-6) play an important role in the adaptation of both muscle and bone to mechanical stimuli. Here, we provide an overview of the functions of IL-6 and IGF-1 in bone and muscle metabolism, and the intracellular signaling pathways that are well

  9. IL-6 and IGF-1 Signaling within, and between, Muscle and Bone: How Important is the mTOR Pathway for Bone Metabolism?

    NARCIS (Netherlands)

    Bakker, A.D.; Jaspers, R.T.

    2015-01-01

    Insulin-like growth factor 1 (IGF-1) and interleukin 6 (IL-6) play an important role in the adaptation of both muscle and bone to mechanical stimuli. Here, we provide an overview of the functions of IL-6 and IGF-1 in bone and muscle metabolism, and the intracellular signaling pathways that are well

  10. 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

  11. IL-6 stabilizes Twist and enhances tumor cell motility in head and neck cancer cells through activation of casein kinase 2.

    Directory of Open Access Journals (Sweden)

    Ying-Wen Su

    Full Text Available BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN is the seventh most common cancer worldwide. Unfortunately, the survival of patients with SCCHN has not improved in the last 40 years, and thus new targets for therapy are needed. Recently, elevations in serum level of interleukin 6 (IL-6 and expression of Twist in tumor samples were found to be associated with poor clinical outcomes in multiple types of cancer, including SCCHN. Although Twist has been proposed as a master regulator of epithelial-mesenchymal transition and metastasis in cancers, the mechanisms by which Twist levels are regulated post-translationally are not completely understood. Tumor progression is characterized by the involvement of cytokines and growth factors and Twist induction has been connected with a number of these signaling pathways including IL-6. Since many of the effects of IL-6 are mediated through activation of protein phosphorylation cascades, this implies that Twist expression must be under a tight control at the post-translational level in order to respond in a timely manner to external stimuli. METHODOLOGY/PRINCIPAL FINDINGS: Our data show that IL-6 increases Twist expression via a transcription-independent mechanism in many SCCHN cell lines. Further investigation revealed that IL-6 stabilizes Twist in SCCHN cell lines through casein kinase 2 (CK2 phosphorylation of Twist residues S18 and S20, and that this phosphorylation inhibits degradation of Twist. Twist phosphorylation not only increases its stability but also enhances cell motility. Thus, post-translational modulation of Twist contributes to its tumor-promoting properties. CONCLUSIONS/SIGNIFICANCE: Our study shows Twist expression can be regulated at the post-translational level through phosphorylation by CK2, which increases Twist stability in response to IL-6 stimulation. Our findings not only provide novel mechanistic insights into post-translational regulation of Twist but also suggest

  12. Expression level and clinical significance of IL-2, IL-6 and TGF-β in elderly patients with goiter and hyperthyroidism.

    Science.gov (United States)

    Lv, L-F; Jia, H-Y; Zhang, H-F; Hu, Y-X

    2017-10-01

    To investigate the level of expression and the clinical significance of IL-2 (interleukin-2), IL-6 (interleukin-6) and TGF-β (transforming growth factor-β) in elderly patients with goiter and hyperthyroidism. Gender, age, course of disease, BMI (Body Mass Index), serum FT3 (Free triiodothyronine-3), FT4 (Free triiodothyronine-4), TT3 (Total triiodothyronine-3), TT4 (Total triiodothyronine-4), TSH (Thyroid Stimulating Hormone) and clinical manifestations on admission and other general clinical data and laboratory examination results were collected and statistically analyzed as case group in 128 elderly patients with goiter and hyperthyroidism. Additional 128 over 60-year-old patients with hyperthyroidism were selected as control group. The thyroid tissue of these patients and the control group were examined by fine needle aspiration biopsy. The expressions of IL-2, IL-6, TGF-β of the thyroid tissue in all patients were detected by immunohistochemistry, qRT-PCR (Real-time Quantitative Polymerase Chain Reaction) and Western blot method respectively, and the statistical analysis was carried out. p hyperthyroidism and thyroid enlargement (p hyperthyroidism, and symptoms of exophthalmos, the level of expression of IL-6 was significantly higher than that of patients without exophthalmos (p hyperthyroidism and symptoms of exophthalmos, and the patients with goiter, hyperthyroidism without symptoms of exophthalmos, IL-2 and TGF-β expression level were not different (p > 0.05). The expression levels of IL-2, IL-6, and TGF-β were significantly increased in the patients with senile goiter and hyperthyroidism, but in the senile patients with goiter, hyperthyroidism and exophthalmos symptoms, IL-6 levels were significantly higher than those without exophthalmos. The use of IL-2, IL-6, and TGF-β is of great significance in the diagnosis of goiter with hyperthyroidism, especially for elderly patients with atypical clinical symptoms of hyperthyroidism.

  13. Plasma interleukin-6 levels, glutathione peroxidase and isoprostane in obese women before and after weight loss. Association with cardiovascular risk factors.

    Science.gov (United States)

    Bougoulia, Maria; Triantos, Athanassios; Koliakos, George

    2006-01-01

    To evaluate the levels of Interleukin-6 (IL-6), glutathione peroxidase and isoprostane in obese women and their association with markers of cardiovascular risk factors before and after weight loss. 36 healthy obese women of reproductive age (group A: age (mean+/-SD) 35.4+/-9.2 years, Body Mass Index (BMI) 38.5+/-7 kg/m2) and 30 healthy, normal weight women (group B: age mean+/-SD 34.9+/-7.4 y., BMI 24+/-1.1 kg/m2) were included in the study. Glucose tolerance was normal in all participating women. Il-6, glutathione peroxidase and isoprostane, C-Reactive Protein (CRP), insulin, fasting plasma glucose, HOMA-IR as well as the lipid profile were evaluated. Body weight, BMI, Waist to Hip ratio (W/H) ratio, Waist Circumference (WC), %free fat mass and the %fat mass were also measured. A hypo-caloric diet was prescribed for the obese women and all participants were re-examined after six months. In obese women after weight loss, anthropometric obesity markers (BMI, W/H ratio), %fat, lipid profile, insulin levels and inflammation indices such as IL-6 and CRP, the oxidative stress index isoprostane, as well as glutathione peroxidase were significantly ameliorated. The levels of serum glutathione peroxidase activity were negatively correlated with IL-6 levels and were significantly increased after weight reduction. In obese women there was an association between IL-6 levels and the values of %fat, %free fat mass, insulin and HOMA-IR before and after weight loss. Weight loss is related to reduction of oxidative stress and inflammation; this beneficial effect could possibly be translated into reduction of cardiovascular risk in obese individuals.

  14. Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Drygin, Denis, E-mail: ddrygin@cylenepharma.com; Ho, Caroline B.; Omori, Mayuko; Bliesath, Joshua; Proffitt, Chris; Rice, Rachel; Siddiqui-Jain, Adam; O' Brien, Sean; Padgett, Claire; Lim, John K.C.; Anderes, Kenna; Rice, William G.; Ryckman, David

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer We examine the potential cross-talk between CK2 and IL-6. Black-Right-Pointing-Pointer Inhibition of CK2 by siRNA or CX-4945 inhibits expression of IL-6 in models of IBC. Black-Right-Pointing-Pointer Treatment of IBC patient in the clinic with CX-4945 reduces her IL-6 plasma levels. Black-Right-Pointing-Pointer We demonstrate that CK2 is a potential therapeutic target for IL-6 driven diseases. -- Abstract: Inflammatory breast cancer is driven by pro-angiogenic and pro-inflammatory cytokines. One of them Interleukin-6 (IL-6) is implicated in cancer cell proliferation and survival, and promotes angiogenesis, inflammation and metastasis. While IL-6 has been shown to be upregulated by several oncogenes, the mechanism behind this phenomenon is not well characterized. Here we demonstrate that the pleotropic Serine/Threonine kinase CK2 is implicated in the regulation of IL-6 expression in a model of inflammatory breast cancer. We used siRNAs targeted toward CK2 and a selective small molecule inhibitor of CK2, CX-4945, to inhibit the expression and thus suppress the secretion of IL-6 in in vitro as well as in vivo models. Moreover, we report that in a clinical trial, CX-4945 was able to dramatically reduce IL-6 levels in plasma of an inflammatory breast cancer patient. Our data shed a new light on the regulation of IL-6 expression and position CX-4945 and potentially other inhibitors of CK2, for the treatment of IL-6-driven cancers and possibly other diseases where IL-6 is instrumental, including rheumatoid arthritis.

  15. The role of IL-6 on apical periodontitis: a systematic review.

    Science.gov (United States)

    Azuma, M M; Samuel, R O; Gomes-Filho, J E; Dezan-Junior, E; Cintra, L T A

    2014-07-01

    The aim of this review was to examine current knowledge of the role of interleukin-6 (IL-6) in apical periodontitis (AP) pathogenesis as an inflammatory or pro-inflammatory cytokine. It also looked at whether IL-6 could serve as a measure for differential diagnosis or as a biomarker that can further predict the progression of bone resorption. A systematic review relating to AP and IL-6 was made via PubMed, BIOSIS, Cochrane, EMBASE and Web of Science databases using keywords and controlled vocabulary. Two independent reviewers first screened titles and abstracts and then the full texts. The reference lists of the identified publications were examined for additional titles. Eighteen papers were studied in total. In vitro studies (n = 6) revealed that IL-6 is present in AP, and its levels are proportional to the size of the periapical lesions. Neutrophils and macrophages resident in these lesions can produce IL-6 in vitro after a bacterial stimulus. Animal studies (n = 5) showed that IL-6 is present in AP and that osteoblasts can produce IL-6 in vivo. On the other hand, two studies using IL-6 knockout mice revealed larger periapical lesions when compared with control groups, demonstrating IL-6's role as an anti-inflammatory cytokine. In human studies (n = 7), IL-6 was identified in AP, and its levels were higher in symptomatic, epithelialized and large lesions than in asymptomatic and small lesions. These data lead to the conclusion that IL-6 may play a pro-inflammatory role, increasing its levels and reabsorbing bone in the presence of infections. When IL-6 is not present, other cytokines such as IL-1 and TNF-α induce bone resorption. Further studies about the relationship between AP development and the cytokine network must be performed to establish the exact role of each cytokine in the inflammatory process. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  16. The Association of Circulating MiR-29b and Interleukin-6 with Subclinical Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Yu-qing Huang

    2017-12-01

    Full Text Available Background/Aims: Although it is widely acknowledged that atherosclerosis is mainly a chronic inflammatory process, in which both miR-29b and interleukin-6 (IL-6 play multifaceted roles, the association between miR-29b and IL-6 remains unknown. The aim of the present study was to explore the relationship between miR-29b and IL-6 and to test whether circulating levels of miR-29b and IL-6 could predict atherosclerosis. Methods: A total of 170 participants were divided into two groups according to carotid intima-media thickness (CIMT: study group (CIMT ≥ 0.9mm and control group (CIMT < 0.9mm. Levels of circulating miR-29b and IL-6 were measured by quantitative real-time polymerase chain reaction (qRT-PCR and enzyme-linked immunosorbent assay (ELISA, respectively. The association of miR-29b and IL-6 levels with CIMT was assessed using Spearman correlation analysis and multiple linear regression analysis. Results: The study group showed higher miR-29b levels (31.61 ± 3.05 vs. 27.91 ± 1.71 Ct, p < 0.001 and IL-6 levels (3.40 ± 0.67 vs. 2.99 ± 0.37 pg/ml, p < 0.001, compared with the control group. CIMT was positively correlated with miR-29b (r = 0.587, p < 0.001 and IL-6 (r = 0.410, p < 0.001, and miR-29b levels were also correlated with IL-6 (r = 0.242, p = 0.001. Multiple linear regression analysis also showed that CIMT was positively correlated with miR-29b and IL-6. After adjustment for age, body mass index, systolic blood pressure, total cholesterol and C-reactive protein, CIMT was still closely correlated with miR-29b and IL-6. The combination of miR-29b and IL-6 (AUC = 0.901, p < 0.001 offered a better predictive index for atherosclerosis than either miR-29b (AUC = 0.867, p < 0.001 or IL-6 (AUC = 0.747, p < 0.001 alone. Conclusion: Circulating levels of miR-29b and IL-6 may be independently correlated with subclinical atherosclerosis, and may serve as novel biomarkers for the identification of atherosclerosis.

  17. Pre-analytical and biological variability in circulating interleukin 6 in healthy subjects and patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Knudsen, Lene S; Christensen, Ib J; Lottenburger, Tine

    2008-01-01

    in serum IL-6 over a 3-year period (14%, p=0.33). Exercise (cycling) increased serum IL-6 in healthy subjects but not in RA patients. In conclusion, circulating IL-6 is stable regarding sample handling and shows little variation over time. Changes in IL-6 concentrations >60% (2 times the biological...... variation) are likely to reflect changes in disease activity and not only pre-analytical or normal biological variability....

  18. [Bone metabolism, biochemical markers of bone resorption and formation processes and interleukine 6 cytokin level during coeliac disease].

    Science.gov (United States)

    Fekih, Monia; Sahli, Hela; Ben Mustapha, Nadia; Mestiri, Imen; Fekih, Moncef; Boubaker, Jalel; Kaabachi, Naziha; Sellami, Mohamed; Kallel, Lamia; Filali, Azza

    2013-01-01

    Celiac disease (CD) is characterized by a malabsorption syndrom. The bone anomalies are one of the principal complications of this disease. The osteoporosis frequency is high: 3.4% among patients having with CD versus 0.2% in the general population. To study the bone mineral density during the CD, to compare it to a control group and to determine the anomalies of biochemical markers of bone turn over and level of interleukin 6 cytokin (IL6) in these patients. All patients with CD have a measurement of bone mineral density by dual-energy x-ray absorptiometry (DXA), a biological exam with dosing calcemia, vitamin D, parathormone (PTH), the osteoblastic bone formation markers (serum osteocalcin, ALP phosphates alkaline), bone osteoclastic activity (C Télopeptide: CTX) and of the IL6. 42 patients were included, with a median age of 33.6 years. 52. 8% of the patients had a low level of D vitamine associated to a high level of PTH. An osteoporosis was noted in 21.5% of patients. No case of osteoporosis was detected in the control group. The mean level of the CTX, ostéocalcine and the IL6 was higher among patients having an osteoporosis or ostéopenia compared to patients with normal bone (p = 0,017). The factors associated with an bone loss (osteopenia or osteoporosis) were: an age > 30 years, a weight 90 UI/ml, an hypo albuminemia < 40 g/l and a level of CTX higher than 1.2. Our study confirms the impact of the CD on the bone mineral statute. The relative risk to have an osteopenia or an osteoporosis was 5 in our series. The measurement of the osseous mineral density would be indicated among patients having a CD.

  19. 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...... 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....... 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

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

    International Nuclear Information System (INIS)

    Yang, R.; Lin, Q.; Gao, H.B.; Zhang, P.

    2014-01-01

    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

  1. 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.

  2. Post-menopausal Women Exhibit Greater Interleukin-6 Responses to Mental Stress Than Older Men.

    Science.gov (United States)

    Endrighi, Romano; Hamer, Mark; Steptoe, Andrew

    2016-08-01

    Acute stress triggers innate immune responses and elevation in circulating cytokines including interleukin-6 (IL-6). The effect of sex on IL-6 responses remains unclear due to important limitations of previous studies. The purpose of this study was to examine sex differences in IL-6 responses to mental stress in a healthy, older (post-menopausal) sample accounting for several moderating factors. Five hundred six participants (62.9 ± 5.60 years, 55 % male) underwent 10 min of mental stress consisting of mirror tracing and Stroop task. Blood was sampled at baseline, after stress, and 45 and 75 min post-stress, and assayed using a high sensitivity kit. IL-6 reactivity was computed as the mean difference between baseline and 45 min and between baseline and 75 min post-stress. Main effects and interactions were examined using ANCOVA models. There was a main effect of time for the IL-6 response (F 3,1512 = 201.57, p = stress compared to males. Results were independent of age, adiposity, socioeconomic position, depression, smoking and alcohol consumption, physical activity, statin use, testing time, task appraisals, hormone replacement, and baseline IL-6. Other significant predictors of IL-6 reactivity were lower household wealth, afternoon testing, and baseline IL-6. Healthy, post-menopausal females exhibit substantially greater IL-6 responses to acute stress. Inflammatory responses if sustained over time may have clinical implications for the development and maintenance of inflammatory-related conditions prevalent in older women.

  3. 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

  4. The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis.

    Science.gov (United States)

    Chang, Qing; Bournazou, Eirini; Sansone, Pasquale; Berishaj, Marjan; Gao, Sizhi Paul; Daly, Laura; Wels, Jared; Theilen, Till; Granitto, Selena; Zhang, Xinmin; Cotari, Jesse; Alpaugh, Mary L; de Stanchina, Elisa; Manova, Katia; Li, Ming; Bonafe, Massimiliano; Ceccarelli, Claudio; Taffurelli, Mario; Santini, Donatella; Altan-Bonnet, Gregoire; Kaplan, Rosandra; Norton, Larry; Nishimoto, Norihiro; Huszar, Dennis; Lyden, David; Bromberg, Jacqueline

    2013-07-01

    We have investigated the importance of interleukin-6 (IL-6) in promoting tumor growth and metastasis. In human primary breast cancers, increased levels of IL-6 were found at the tumor leading edge and positively correlated with advanced stage, suggesting a mechanistic link between tumor cell production of IL-6 and invasion. In support of this hypothesis, we showed that the IL-6/Janus kinase (JAK)/signal transducer and activator of transcription 3 (Stat3) pathway drives tumor progression through the stroma and metastatic niche. Overexpression of IL-6 in tumor cell lines promoted myeloid cell recruitment, angiogenesis, and induced metastases. We demonstrated the therapeutic potential of interrupting this pathway with IL-6 receptor blockade or by inhibiting its downstream effectors JAK1/2 or Stat3. These clinically relevant interventions did not inhibit tumor cell proliferation in vitro but had profound effects in vivo on tumor progression, interfering broadly with tumor-supportive stromal functions, including angiogenesis, fibroblast infiltration, and myeloid suppressor cell recruitment in both the tumor and pre-metastatic niche. This study provides the first evidence for IL-6 expression at the leading edge of invasive human breast tumors and demonstrates mechanistically that IL-6/JAK/Stat3 signaling plays a critical and pharmacologically targetable role in orchestrating the composition of the tumor microenvironment that promotes growth, invasion, and metastasis.

  5. The IL-6/JAK/Stat3 Feed-Forward Loop Drives Tumorigenesis and Metastasis12

    Science.gov (United States)

    Chang, Qing; Bournazou, Eirini; Sansone, Pasquale; Berishaj, Marjan; Gao, Sizhi Paul; Daly, Laura; Wels, Jared; Theilen, Till; Granitto, Selena; Zhang, Xinmin; Cotari, Jesse; Alpaugh, Mary L; de Stanchina, Elisa; Manova, Katia; Li, Ming; Bonafe, Massimiliano; Ceccarelli, Claudio; Taffurelli, Mario; Santini, Donatella; Altan-Bonnet, Gregoire; Kaplan, Rosandra; Norton, Larry; Nishimoto, Norihiro; Huszar, Dennis; Lyden, David; Bromberg, Jacqueline

    2013-01-01

    We have investigated the importance of interleukin-6 (IL-6) in promoting tumor growth and metastasis. In human primary breast cancers, increased levels of IL-6 were found at the tumor leading edge and positively correlated with advanced stage, suggesting a mechanistic link between tumor cell production of IL-6 and invasion. In support of this hypothesis, we showed that the IL-6/Janus kinase (JAK)/signal transducer and activator of transcription 3 (Stat3) pathway drives tumor progression through the stroma and metastatic niche. Overexpression of IL-6 in tumor cell lines promoted myeloid cell recruitment, angiogenesis, and induced metastases. We demonstrated the therapeutic potential of interrupting this pathway with IL-6 receptor blockade or by inhibiting its downstream effectors JAK1/2 or Stat3. These clinically relevant interventions did not inhibit tumor cell proliferation in vitro but had profound effects in vivo on tumor progression, interfering broadly with tumor-supportive stromal functions, including angiogenesis, fibroblast infiltration, and myeloid suppressor cell recruitment in both the tumor and pre-metastatic niche. This study provides the first evidence for IL-6 expression at the leading edge of invasive human breast tumors and demonstrates mechanistically that IL-6/JAK/Stat3 signaling plays a critical and pharmacologically targetable role in orchestrating the composition of the tumor microenvironment that promotes growth, invasion, and metastasis. PMID:23814496

  6. The IL-6/JAK/Stat3 Feed-Forward Loop Drives Tumorigenesis and Metastasis

    Directory of Open Access Journals (Sweden)

    Qing Chang

    2013-07-01

    Full Text Available We have investigated the importance of interleukin-6 (IL-6 in promoting tumor growth and metastasis. In human primary breast cancers, increased levels of IL-6 were found at the tumor leading edge and positively correlated with advanced stage, suggesting a mechanistic link between tumor cell production of IL-6 and invasion. In support of this hypothesis, we showed that the IL-6/Janus kinase (JAK/signal transducer and activator of transcription 3 (Stat3 pathway drives tumor progression through the stroma and metastatic niche. Overexpression of IL-6 in tumor cell lines promoted myeloid cell recruitment, angiogenesis, and induced metastases. We demonstrated the therapeutic potential of interrupting this pathway with IL-6 receptor blockade or by inhibiting its downstream effectors JAK1/2 or Stat3. These clinically relevant interventions did not inhibit tumor cell proliferation in vitro but had profound effects in vivo on tumor progression, interfering broadly with tumor-supportive stromal functions, including angiogenesis, fibroblast infiltration, and myeloid suppressor cell recruitment in both the tumor and pre-metastatic niche. This study provides the first evidence for IL-6 expression at the leading edge of invasive human breast tumors and demonstrates mechanistically that IL-6/JAK/Stat3 signaling plays a critical and pharmacologically targetable role in orchestrating the composition of the tumor microenvironment that promotes growth, invasion, and metastasis.

  7. Role of the IL-6 Gene in the Etiopathogenesis of Idiopathic Scoliosis

    Directory of Open Access Journals (Sweden)

    Svetla Nikolova

    2015-01-01

    Full Text Available Scoliotic human nuclei pulposi can respond to exogenous proinflammatory stimuli by secreting increased amounts of interleukin-6 (IL-6. The G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein. We conducted a case-control study of eighty patients with idiopathic scoliosis (IS and one hundred sixty healthy unrelated gender-matched controls trying to investigate the association between IS and the IL-6 promoter polymorphism at -174 position (rs1800795 G/C in Bulgarian population. Molecular detection of the IL-6 genotypes was performed by amplification followed by restriction technology. The statistical analysis was performed by Pearson’s chi-squared test. Our case-control study revealed a statistically significant association between the IL-6 (-174 G/C functional polymorphism and susceptibility to IS. In addition, a significant association between the IL-6 (-174 G/C polymorphism and curve severity was detected. IL-6 gene could be considered as susceptibility and modifying factor of idiopathic scoliosis. The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of scoliosis and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures.

  8. Impairment of Hepcidin Upregulation by Lipopolysaccharide in the Interleukin-6 Knockout Mouse Brain

    Directory of Open Access Journals (Sweden)

    Fa-Li Zhang

    2017-11-01

    Full Text Available To find out whether the Interleukin-6 (IL-6/signal transducer and activator of transcription 3 (STAT3 signaling pathway is involved in the expression of hepcidin in the mouse brain in vivo, we investigated the phosphorylation of STAT3, as well as the expression of hepcidin mRNA, ferroportin 1 (Fpn1 and ferritin light chain (Ft-L proteins in the cortex and hippocampus of LPS-treated wild type (IL-6+/+ and IL-6 knockout (IL-6-/- mice. We demonstrated that IL-6 knockout could significantly reduce the response of hepcidin mRNA, phospho-STAT3, Fpn1 and Ft-L protein expression to LPS treatment, in both the cortex and hippocampus of mice. Also, Stattic, an inhibitor of STAT3, significantly reduced the expression of phospho-STAT3 and hepcidin mRNA in the cortex and hippocampus of the LPS-treated wild type mice. These findings provide in vivo evidence for the involvement of the IL-6/STAT3 signaling pathway in the expression of hepcidin.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Elevated Circulating IL-1β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome

    Directory of Open Access Journals (Sweden)

    Nicolaos Vitoratos

    2006-01-01

    Full Text Available The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1β (IL-1β, tumor necrosis factor alpha (TNF-alpha, and Th2-type cytokine interleukin 6 (IL-6 were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1 and discharge (group B2 and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1β and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1β, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome.

  14. Elevated Circulating IL-1β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome

    Science.gov (United States)

    Vitoratos, Nicolaos; Papadias, Constantinos; Economou, Emmanuel; Makrakis, Evangelos; Panoulis, Constantinos; Creatsas, George

    2006-01-01

    The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1) and discharge (group B2) and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C) who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1β and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1β, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome. PMID:17047289

  15. Elevated Circulating IL-1 β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1 β (IL-1 β , tumor necrosis factor alpha (TNF-alpha, and Th2-type cytokine interleukin 6 (IL-6 were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1 and discharge (group B2 and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1 β and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1 β , TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome.

  16. Elevated circulating IL-1beta and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome.

    Science.gov (United States)

    Vitoratos, Nicolaos; Papadias, Constantinos; Economou, Emmanuel; Makrakis, Evangelos; Panoulis, Constantinos; Creatsas, George

    2006-01-01

    The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1) and discharge (group B2) and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C) who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1beta and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1beta, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome.

  17. Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy.

    Science.gov (United States)

    Linnemann, Amelia K; Blumer, Joseph; Marasco, Michelle R; Battiola, Therese J; Umhoefer, Heidi M; Han, Jee Young; Lamming, Dudley W; Davis, Dawn Belt

    2017-09-01

    IL-6 is a pleiotropic cytokine with complex roles in inflammation and metabolic disease. The role of IL-6 as a pro- or anti-inflammatory cytokine is still unclear. Within the pancreatic islet, IL-6 stimulates secretion of the prosurvival incretin hormone glucagon-like peptide 1 (GLP-1) by α cells and acts directly on β cells to stimulate insulin secretion in vitro Uncovering physiologic mechanisms promoting β-cell survival under conditions of inflammation and stress can identify important pathways for diabetes prevention and treatment. Given the established role of GLP-1 in promoting β-cell survival, we hypothesized that IL-6 may also directly protect β cells from apoptosis. Herein, we show that IL-6 robustly activates signal transducer and activator of transcription 3 (STAT3), a transcription factor that is involved in autophagy. IL-6 stimulates LC3 conversion and autophagosome formation in cultured β cells. In vivo IL-6 infusion stimulates a robust increase in lysosomes in the pancreas that is restricted to the islet. Autophagy is critical for β-cell homeostasis, particularly under conditions of stress and increased insulin demand. The stimulation of autophagy by IL-6 is regulated via multiple complementary mechanisms including inhibition of mammalian target of rapamycin complex 1 (mTORC1) and activation of Akt, ultimately leading to increases in autophagy enzyme production. Pretreatment with IL-6 renders β cells resistant to apoptosis induced by proinflammatory cytokines, and inhibition of autophagy with chloroquine prevents the ability of IL-6 to protect from apoptosis. Importantly, we find that IL-6 can activate STAT3 and the autophagy enzyme GABARAPL1 in human islets. We also see evidence of decreased IL-6 pathway signaling in islets from donors with type 2 diabetes. On the basis of our results, we propose direct stimulation of autophagy as a novel mechanism for IL-6-mediated protection of β cells from stress-induced apoptosis.-Linnemann, A. K

  18. Astrocytic IL-6 mediates locomotor activity, exploration, anxiety, learning and social behavior.

    Science.gov (United States)

    Erta, Maria; Giralt, Mercedes; Esposito, Flavia Lorena; Fernandez-Gayol, Olaya; Hidalgo, Juan

    2015-07-01

    Interleukin-6 (IL-6) is a major cytokine in the central nervous system, secreted by different brain cells and with roles in a number of physiological functions. We herewith confirm and expand the importance of astrocytic production of and response to IL-6 by using transgenic mice deficient in astrocytic IL-6 (Ast-IL-6 KO) or in its receptor (Ast-IL-6R KO) in full C57Bl/6 genetic background. A major prosurvival effect of astrocytic IL-6 at early ages was clearly demonstrated. Robust effects were also evident in the control of activity and anxiety in the hole-board and elevated plus-maze, and in spatial learning in the Morris water-maze. The results also suggest an inhibitory role of IL-6 in the mechanism controlling the consolidation of hippocampus-dependent spatial learning. Less robust effects of astrocytic IL-6 system were also observed in despair behavior in the tail suspension test, and social behavior in the dominance and resident-intruder tests. The behavioral phenotype was highly dependent on age and/or sex in some cases. The phenotype of Ast-IL-6R KO mice mimicked only partially that of Ast-IL-6KO mice, which indicates both a role of astrocytes in behavior and the participation of other cells besides astrocytes. No evidences of altered function of the hypothalamic-pituitary-adrenal axis were observed. These results demonstrate that astrocytic IL-6 (acting at least partially in astrocytes) regulates normal behavior in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Skeletal muscle mass recovery from atrophy in IL-6 knockout mice.

    Science.gov (United States)

    Washington, T A; White, J P; Davis, J M; Wilson, L B; Lowe, L L; Sato, S; Carson, J A

    2011-08-01

    Skeletal muscle interleukin-6 (IL-6) expression is induced by continuous contraction, overload-induced hypertrophy and during muscle regeneration. The loss of IL-6 can alter skeletal muscle's growth and extracellular matrix remodelling response to overload-induced hypertrophy. Insulin-like growth factor-1 (IGF-1) gene expression and related signalling through Akt/mTOR is a critical regulator of muscle mass. The significance of IL-6 expression during the recovery from muscle atrophy is unclear. This study's purpose was to determine the effect of IL-6 loss on mouse gastrocnemius (GAS) muscle mass during recovery from hindlimb suspension (HS)-induced atrophy. Female C57BL/6 [wild type (WT)] and IL-6 knockout (IL-6 KO) mice at 10 weeks of age were assigned to control, HS or HS followed by normal cage ambulation groups. GAS muscle atrophy was induced by 10 days of HS. HS induced a 20% loss of GAS mass in both WT and IL-6 KO mice. HS+7 days of recovery restored WT GAS mass to cage-control values. GAS mass from IL-6 KO mice did not return to cage-control values until HS+14 days of recovery. Both IGF-1 mRNA expression and Akt/mTOR signalling were increased in WT muscle after 1 day of recovery. In IL-6 KO muscle, IGF-1 mRNA expression was decreased and Akt/mTOR signalling was not induced after 1 day of recovery. MyoD and myogenin mRNA expression were both induced in WT muscle after 1 day of recovery, but not in IL-6 KO muscle.   Muscle IL-6 expression appears important for the initial growth response during the recovery from disuse. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  20. Interleukin-6 promotes systemic lupus erythematosus progression with Treg suppression approach in a murine systemic lupus erythematosus model.

    Science.gov (United States)

    Mao, Xiaoli; Wu, Yunyun; Diao, Huitian; Hao, Jianlei; Tian, Gaofei; Jia, Zhenghu; Li, Zheng; Xiong, Sidong; Wu, Zhenzhou; Wang, Puyue; Zhao, Liqing; Yin, Zhinan

    2014-11-01

    Our aim is to reveal the role of interleukin 6 (IL-6) in the pathogenesis of systemic lupus erythematosus (SLE) in a murine model of SLE. Normal female C57BL/6 mice were immunized with syngeneic-activated lymphocyte-derived DNA (ALD-DNA) to induce SLE. Non-immunized mice were used as control. SLE-associated markers, including anti-double-stranded DNA (anti-dsDNA) Abs, urine protein, and kidney histopathology, were assayed to ensure the induction of the disease. Compared with control mice, ALD-DNA immunized mice exhibited high levels of anti-dsDNA Abs, IL-6 expression in vivo and in vitro. We also found that IL-6 knockout (IL-6KO) mice were resistant to ALD-DNA-induced SLE. The activation of CD4(+) T cells in immunized IL-6KO mice was lower than in immunized wild-type (Wt) mice. Intracellular cytokine staining showed that Foxp3 expression in immunized IL-6KO mice was higher than in immunized Wt mice, which might be associated with the disease severity. We further discovered that ALD-DNA-stimulated dendritic cells supernatants could result in higher IL-6 and TNF-α expression and could suppress Foxp3 expression. In addition, blocking IL-6 could up-regulate Foxp3 expression. Therefore, our findings show that IL-6 promotes the progression of SLE via suppressing Treg differentiation.

  1. Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human adamantinomatous craniopharyngioma cells and promotes tumor cell migration

    Science.gov (United States)

    Zhou, Jie; Zhang, Chao; Pan, Jun; Chen, Ligang; Qi, Song-Tao

    2017-01-01

    Total resection of adamantinomatous craniopharyngioma (ACP) is complex and often leads to postoperative recurrence. This is due to the tendency of the tumor to invade the surrounding brain tissue and the generation of a local inflammatory state between the tumor cells and parenchyma. While there is evidence to suggest that interleukin-6 (IL-6) induces craniopharyngioma (CP)-associated inflammation, particularly in ACP, the role of IL-6 in the progression of ACP remains unclear. The results of the present study demonstrated that CP inflammation was associated with pathological classification, extent of surgery, degree of calcification and postoperative hypothalamic status scale. Cytokine antibody arrays were conducted to measure the expression of IL-6 and other inflammatory factors in tumor tissues in response to various levels of inflammatory exposure. IL-6, IL-6 receptor (IL-6R) and glycoprotein 130 expression was detected by immunohistochemistry. In addition, an ELISA was performed to quantify the levels of soluble IL-6R (sIL-6R) in the cystic fluid and supernatants of ACP cells and tumor-associated fibroblasts. These measurements demonstrated that ACP cells produce IL-6 and its associated proteins. In addition, the results revealed that while the viability of ACP cells was not affected, the migration of ACP cells was promoted by IL-6 treatment in a concentration-dependent manner. Conversely, treatment with an IL-6-blocking monoclonal antibody significantly decreased the migration of ACP cells. In addition, IL-6 treatment increased the expression of vimentin and decreased the expression of E-cadherin in a dose-dependent manner. The findings of the present study demonstrate that IL-6 may promote migration in vitro via the classic- and trans-signaling pathways by inducing epithelial-mesenchymal transition in ACP cell cultures. PMID:28487953

  2. Treatment with the anti-IL-6 receptor antibody attenuates muscular dystrophy via promoting skeletal muscle regeneration in dystrophin-/utrophin-deficient mice.

    Science.gov (United States)

    Wada, Eiji; Tanihata, Jun; Iwamura, Akira; Takeda, Shin'ichi; Hayashi, Yukiko K; Matsuda, Ryoichi

    2017-10-27

    Chronic increases in the levels of the inflammatory cytokine interleukin-6 (IL-6) in serum and skeletal muscle are thought to contribute to the progression of muscular dystrophy. Dystrophin/utrophin double-knockout (dKO) mice develop a more severe and progressive muscular dystrophy than the mdx mice, the most common murine model of Duchenne muscular dystrophy (DMD). In particular, dKO mice have smaller body sizes and muscle diameters, and develop progressive kyphosis and fibrosis in skeletal and cardiac muscles. As mdx mice and DMD patients, we found that IL-6 levels in the skeletal muscle were significantly increased in dKO mice. Thus, in this study, we aimed to analyze the effects of IL-6 receptor (IL-6R) blockade on the muscle pathology of dKO mice. Male dKO mice were administered an initial injection (200 mg/kg intraperitoneally (i.p.)) of either the anti-IL-6R antibody MR16-1 or an isotype-matched control rat IgG at the age of 14 days, and were then given weekly injections (25 mg/kg i.p.) until 90 days of age. Treatment of dKO mice with the MR16-1 antibody successfully inhibited the IL-6 pathway in the skeletal muscle and resulted in a significant reduction in the expression levels of phosphorylated signal transducer and activator of transcription 3 in the skeletal muscle. Pathologically, a significant increase in the area of embryonic myosin heavy chain-positive myofibers and muscle diameter, and reduced fibrosis in the quadriceps muscle were observed. These results demonstrated the therapeutic effects of IL-6R blockade on promoting muscle regeneration. Consistently, serum creatine kinase levels were decreased. Despite these improvements observed in the limb muscles, degeneration of the diaphragm and cardiac muscles was not ameliorated by the treatment of mice with the MR16-1 antibody. As no adverse effects of treatment with the MR16-1 antibody were observed, our results indicate that the anti-IL-6R antibody is a potential therapy for muscular dystrophy

  3. Interleukin-6 from subchondral bone mesenchymal stem cells contributes to the pathological phenotypes of experimental osteoarthritis

    Science.gov (United States)

    Wu, Xiaofeng; Cao, Lei; Li, Fan; Ma, Chao; Liu, Guangwang; Wang, Qiugen

    2018-01-01

    As a main cause of morbidity in the aged population, osteoarthritis (OA) is characterized by cartilage destruction, synovium inflammation, osteophytes, and subchondral bone sclerosis. To date its etiology remains elusive. Recent data highlight an important role of subchondral bone in the onset and progression of OA. Therefore, elucidating the mechanisms underlying abnormal subchondral bone could be of importance in the treatment of OA. Interleukin-6 is a proinflammatory cytokine involved in many physiological and pathological processes. Although in vitro and in vivo studies have indicated that IL-6 is an important cytokine in the physiopathogenesis of OA, its effects on subchondral bone have not been studied in OA animal models. In this study, we aimed to i) investigate the role of IL-6 in the pathological phenotypes of OA subchondral bone MSCs including increase in cell numbers, mineralization disorder and abnormal type I collagen production; ii) explore whether the systemic blockade of IL-6 signaling could alleviate the pathological phenotypes of experimental OA. We found that IL-6 was over-secreted by OA subchondral bone MSCs compared with normal MSCs and IL-6/STAT3 signaling was over-activated in subchondral bone MSCs, which contributed to the pathological phenotypes of OA subchondral bone MSCs. More importantly, systemic inhibition of IL-6/STAT3 signaling with IL-6 antibody or STAT3 inhibitor AG490 decreased the severity of pathological phenotypes of OA subchondral bone MSCs and cartilage lesions in OA. Our findings provide strong evidence for a pivotal role for IL-6 signaling in OA and open up new therapeutic perspectives. PMID:29736207

  4. 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.

  5. The release of endotoxin, TNF and IL-6 during the antibiotic treatment of experimental Gram-negative sepsis

    NARCIS (Netherlands)

    Dofferhoff, A.S.M.; Potthoff, H.; Bom, V.J.J.; Bartels, H.L.; De Vries-Hospers, H.G.; Bijzet, J.; Weits, J.; Buurman, W.; Bleichrodt, R.P.

    1995-01-01

    To evaluate the role of different antibiotics in the release of endotoxin and the production of tumor necrosis factor-α (TNF) and interleukin 6 (IL-6) during the treatment of experimental Escherichia coli septical peritonitis, we obtained serial blood samples from septic rats treated with placebo,

  6. SIMULTANEOUS EXPRESSION AND REGULATION OF G-CSF AND IL-6 MESSENGER-RNA IN ADHERENT HUMAN MONOCYTES AND FIBROBLASTS

    NARCIS (Netherlands)

    VELLENGA, E; VANDERVINNE, B; DEWOLF, JTM; HALIE, MR

    The regulation of granulocyte-colony stimulating factor (G-CSF) and interleukin-6 (IL-6) mRNA was studied in human adherent monocytes in response to the protein kinase C activator, oleolyl-acetylglycerol (OAG), the calcium-ionophore A23187 and the cyclic AMP elevating agents, dibutyryl c-AMP

  7. Factors Associated With Plasma IL-6 Levels During HIV Infection

    DEFF Research Database (Denmark)

    Borges, Álvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2015-01-01

    (Strategies for Management of Anti-Retroviral Therapy) trial, CD4/CD8 ratio, smoking, comorbid conditions, serum lipids, renal function (estimated glomerular filtration rate [eGFR]), and educational level were assessed. RESULTS: Demographics associated with higher IL-6 levels were older age and lower...

  8. IL-6 Receptor Isoforms and Ovarian Cancer

    Science.gov (United States)

    2013-01-01

    grown these cells in culture and have generated stable cell clones which express Tomato Red so that these cells can be followed through fluorescent...occurring in ovarian cell lines, we examined the effect of IL6 and IL6Ra expression on cell migration in vitro . Migration through uncoated cell culture ...or IL6R were plated on tissue culture plates and scratch wounds were made. Over the course of the experiment, photographs of the cultures were

  9. 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

  10. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis.

    Science.gov (United States)

    Latourte, Augustin; Cherifi, Chahrazad; Maillet, Jérémy; Ea, Hang-Korng; Bouaziz, Wafa; Funck-Brentano, Thomas; Cohen-Solal, Martine; Hay, Eric; Richette, Pascal

    2017-04-01

    To investigate the impact of systemic inhibition of interleukin 6 (IL-6) or signal transducer and activator of transcription (Stat3) in an experimental model of osteoarthritis (OA). Expression of major catabolic and anabolic factors of cartilage was determined in IL-6-treated mouse chondrocytes and cartilage explants. The anti-IL-6-receptor neutralising antibody MR16-1 was used in the destabilisation of the medial meniscus (DMM) mouse model of OA. Stat3 blockade was investigated by the small molecule Stattic ex vivo and in the DMM model. In chondrocytes and cartilage explants, IL-6 treatment reduced proteoglycan content with increased production of matrix metalloproteinase (MMP-3 and MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4 and ADAMTS-5). IL-6 induced Stat3 and extracellular signal-regulated kinase (ERK) 1/2 signalling but not p38, c-Jun N-terminal kinase or Akt. In the DMM model, Stat3 was activated in cartilage, but neither in the synovium nor in the subchondral bone. Systemic blockade of IL-6 by MR16-1 alleviated DMM-induced OA cartilage lesions, impaired the osteophyte formation and the extent of synovitis. In the same model, Stattic had similar beneficial effects on cartilage and osteophyte formation. Stattic, but not an ERK1/2 inhibitor, significantly counteracted the catabolic effects of IL-6 on cartilage explants and suppressed the IL-6-induced chondrocytes apoptosis. IL-6 induces chondrocyte catabolism mainly via Stat3 signalling, a pathway activated in cartilage from joint subjected to DMM. Systemic blockade of IL-6 or STAT-3 can alleviate DMM-induced OA in mice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. 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......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......-phase proportion of myeloma cells, which might increase the sensitivity to chemotherapy, we gave rhIL-6 followed by chemotherapy to 15 myeloma patients with refractory disease. A total of 25 treatment cycles were administered since ten patients had two cycles. The rhIL-6 dose was 2.5 (n = 3), 5.0 (n = 6) and 10...

  12. Correlation between Interleukin-6 and Thrombin-Antithrombin III Complex Levels in Retinal Diseases.

    Science.gov (United States)

    Ehrlich, Rita; Zahavi, Alon; Axer-Siegel, Ruth; Budnik, Ivan; Dreznik, Ayelet; Dahbash, Mor; Nisgav, Yael; Megiddo, Elinor; Kenet, Gili; Weinberger, Dov; Livnat, Tami

    2017-09-01

    This study aims to evaluate and correlate the levels of interleukin-6 (IL-6) and thrombin-antithrombin III complex (TAT) in the vitreous of patients with different vitreoretinal pathologies. Vitreous samples were collected from 78 patients scheduled for pars plana vitrectomy at a tertiary medical center. Patients were divided by the underlying vitreoretinal pathophysiology, as follows: macular hole (MH)/epiretinal membrane (ERM) (n = 26); rhegmatogenous retinal detachment (RRD) (n = 32); and proliferative diabetic retinopathy (PDR) (n = 20). Levels of IL-6 and TAT were measured by enzyme-linked immunosorbent assay and compared among the groups. A significant difference was found in the vitreal IL-6 and TAT levels between the MH/ERM group and both the PDR and RRD groups (P Diabetes was associated with higher IL-6 levels in the RRD group. Different relationships between the IL-6 and TAT levels were revealed in patients with different ocular pathologies. Our results imply that variations in vitreal TAT level may be attributable not only to an inflammatory reaction or blood-retinal barrier breakdown, but also to intraocular tissue-dependent regulation of thrombin.

  13. Evaluation of salivary interleukin-6 in children with early childhood caries after treatment

    Directory of Open Access Journals (Sweden)

    Medhini Madhavan Menon

    2016-01-01

    Full Text Available Background: The role of cytokines as a marker in the oral inflammatory process in ECC has not been fully explored before and after full mouth rehabilitation. Aims: The aim of this study was to assess the level of salivary interleukin-6 (IL-6 in children with ECC and to compare its levels before and after comprehensive full mouth rehabilitation. Methods and Materials: Saliva samples were collected from children with ECC prior to dental treatment and 3-month post treatment. The salivary IL-6 levels were analyzed using the ELISA method. The gingival index was also timely recorded. Oral health awareness sessions were conducted for children and their parents at regular intervals during the 3-month study period. Statistical analysis used: Wilcoxon Signed Rank test compared the levels of salivary IL-6 while, the paired t test compared the values of gingival index before and after treatment. Results: The mean level of salivary IL-6 before and 3 months after treatment had reduced and this reduction was statistically significant (P< 0.000. The gingival index scores had also reduced significantly 3-months post treatment (P< 0.002. Conclusions: Children with ECC when completely rehabilitated and kept under frequent follow up, which includes reinforcement of oral hygiene measures and maintaining a low caries activity state, the level of inflammation (IL-6 can definitely be minimized and thereby improving the quality of life of affected children.

  14. 17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seulki, E-mail: sl10f@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Minjong, E-mail: minjonglee2@naver.com [Division of Gastroenterology, Department of Internal Medicine, Kangwon National University Hospital, 156 Baengnyeong-ro, Chuncheon-si, Gangwon-do (Korea, Republic of); Kim, Jong Bin, E-mail: kkimjp@hanmail.net [Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN, 55912 (United States); Jo, Ara, E-mail: loveara0315@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Cho, Eun Ju, E-mail: creatioex@gmail.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yu, Su Jong, E-mail: ydoctor2@hanmail.net [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Jeong-Hoon, E-mail: pindra@empal.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yoon, Jung-Hwan, E-mail: yoonjh@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Kim, Yoon Jun, E-mail: yoonjun@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of)

    2016-05-13

    17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. -- Highlights: •Anoikis-resistant HCC cells characterized chemo-resistant and metastatic potentials. •17β-Estradiol down-regulated IL-6/STAT3 signaling in anoikis-resistant HCC cells. •17β-Estradiol suppressed cell proliferation by inducing G2/M phase arrest and apoptosis though JNK phosphorylation.

  15. IL6R Variation Asp358Ala Is a Potential Modifier of Lung Function in Asthma

    Science.gov (United States)

    Hawkins, Gregory A; Robinson, Mac B; Hastie, Annette T; Li, Xingnan; Li, Huashi; Moore, Wendy C; Howard, Timothy D; Busse, William W.; Erzurum, Serpil C.; Wenzel, Sally E.; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

    2012-01-01

    Background The IL6R SNP rs4129267 has recently been identified as an asthma susceptibility locus in subjects of European ancestry but has not been characterized with respect to asthma severity. The SNP rs4129267 is in linkage disequilibrium (r2=1) with the IL6R coding SNP rs2228145 (Asp358Ala). This IL6R coding change increases IL6 receptor shedding and promotes IL6 transsignaling. Objectives To evaluate the IL6R SNP rs2228145 with respect to asthma severity phenotypes. Methods The IL6R SNP rs2228145 was evaluated in subjects of European ancestry with asthma from the Severe Asthma Research Program (SARP). Lung function associations were replicated in the Collaborative Study on the Genetics of Asthma (CSGA) cohort. Serum soluble IL6 receptor (sIL6R) levels were measured in subjects from SARP. Immunohistochemistry was used to qualitatively evaluate IL6R protein expression in BAL cells and endobronchial biopsies. Results The minor C allele of IL6R SNP rs2228145 was associated with lower ppFEV1 in the SARP cohort (p=0.005), the CSGA cohort (0.008), and in combined cohort analysis (p=0.003). Additional associations with ppFVC, FEV1/FVC, and PC20 were observed. The rs2228145 C allele (Ala358) was more frequent in severe asthma phenotypic clusters. Elevated serum sIL6R was associated with lower ppFEV1 (p=0.02) and lower ppFVC (p=0.008) (N=146). IL6R protein expression was observed in BAL macrophages, airway epithelium, vascular endothelium, and airway smooth muscle. Conclusions The IL6R coding SNP rs2228145 (Asp358Ala) is a potential modifier of lung function in asthma and may identify subjects at risk for more severe asthma. IL6 transsignaling may have a pathogenic role in the lung. PMID:22554704

  16. A Paracrine Role for IL6 in Prostate Cancer Patients: Lack of Production by Primary or Metastatic Tumor Cells

    Science.gov (United States)

    Yu, Shu-Han; Zheng, Qizhi; Esopi, David; Macgregor-Das, Anne; Luo, Jun; Antonarakis, Emmanuel S.; Drake, Charles G.; Vessella, Robert; Morrissey, Colm; De Marzo, Angelo M.; Sfanos, Karen S.

    2015-01-01

    Correlative human studies suggest that the pleiotropic cytokine interleukin-6 (IL6) contributes to the development and/or progression of prostate cancer. However, the source of IL6 production in the prostate microenvironment in patients has yet to be determined. The cellular origin of IL6 in primary and metastatic prostate cancer was examined in formalin-fixed, paraffin-embedded (FFPE) tissues using a highly sensitive and specific chromogenic in situ hybridization (CISH) assay that underwent extensive analytical validation. Quantitative RT-PCR (q-RT-PCR) showed that benign prostate tissues often had higher expression of IL6 mRNA than matched tumor specimens. CISH analysis further indicated that both primary and metastatic prostate adenocarcinoma cells do not express IL6 mRNA. IL6 expression was highly heterogeneous across specimens and was nearly exclusively restricted to the prostate stromal compartment – including endothelial cells and macrophages among other cell types. The number of IL6-expressing cells correlated positively with the presence of acute inflammation. In metastatic disease, tumor cells were negative in all lesions examined and IL6 expression was restricted to endothelial cells within the vasculature of bone metastases. Finally, IL6 was not detected in any cells in soft tissue metastases. These data suggest that, in prostate cancer patients, paracrine rather than autocrine IL6 production is likely associated with any role for the cytokine in disease progression. PMID:26048576

  17. Evaluation of anti-IL-6 monoclonal antibody therapy using murine type II collagen-induced arthritis

    Directory of Open Access Journals (Sweden)

    Shealy David

    2009-04-01

    Full Text Available Abstract Interleukin-6 is a multifunctional cytokine that is critical for T/B-cell differentiation and maturation, immunoglobulin secretion, acute-phase protein production, and macrophage/monocyte functions. Extensive research into the biology of IL-6 has implicated IL-6 in the pathophysiology and pathogenesis of RA. An anti-murine IL-6 mAb that neutralizes mouse IL-6 activities was tested in animal model of collagen-induced arthritis. Prophylactic treatment with anti-IL-6 mAb significantly reduced the incidence and severity of arthritis compared to control mAb treated mice. The mitogenic response of B and T cells isolated from the lymph nodes of anti-IL-6 treated mice was significantly reduced compared to cells isolated from control mAb treated mice. The overall histopathology score for paws from the anti-IL-6 treated mice was significantly reduced when compared to paws from mice treated with control mAb, including both inflammatory (synovitis and pannus and erosive (erosions and architecture parameters. Reduced loss of cartilage matrix components was also observed in the anti-IL-6 treated mice. Collectively, these data suggest that IL-6 plays a major role in the pathophysiology of rheumatoid arthritis, and thus support the potential benefit of anti-IL-6 mAb treatment in rheumatoid arthritis patients.

  18. 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.

  19. 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

  20. Low Oxygen Consumption is Related to a Hypomethylation and an Increased Secretion of IL-6 in Obese Subjects with Sleep Apnea-Hypopnea Syndrome.

    Science.gov (United States)

    Lopez-Pascual, Amaya; Lasa, Arrate; Portillo, María P; Arós, Fernando; Mansego, María L; González-Muniesa, Pedro; Martinez, J Alfredo

    2017-01-01

    Deoxyribonucleic acid (DNA) methylation is an epigenetic modification involved in gene expression regulation, usually via gene silencing, which contributes to the risks of many multifactorial diseases. The aim of the present study was to analyze the influence of resting oxygen consumption on global and gene DNA methylation as well as protein secretion of inflammatory markers in blood cells from obese subjects with sleep apnea-hypopnea syndrome (SAHS). A total of 44 obese participants with SAHS were categorized in 2 groups according to their resting oxygen consumption. DNA methylation levels were evaluated using a methylation-sensitive high resolution melting approach. The analyzed interleukin 6 (IL6) gene cytosine phosphate guanine (CpG) islands showed a hypomethylation, while serum IL-6 was higher in the low compared to the high oxygen consumption group (p DNA methylation of tumor necrosis factor (B = -0.82, 95% CI -1.33 to -0.30) and long interspersed nucleotide element 1 (B = -0.46; 95% CI -0.87 to -0.04) gene CpGs were found. Finally, studied CpG methylation levels of serpin peptidase inhibitor, clade E member 1 (r = 0.43; p = 0.01), and IL6 (r = 0.41; p = 0.02) were positively associated with fat-free mass. These findings suggest a potential role of oxygen in the regulation of inflammatory genes. Oxygen consumption measurement at rest could be proposed as a clinical biomarker of metabolic health. © 2017 S. Karger AG, Basel.

  1. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma.

    Science.gov (United States)

    Sapan, Heber Bombang; Paturusi, Idrus; Jusuf, Irawan; Patellongi, Ilhamjaya; Massi, Muh Nasrum; Pusponegoro, Aryono Djuned; Arief, Syafrie Kamsul; Labeda, Ibrahim; Islam, Andi Asadul; Rendy, Leo; Hatta, Mochammad

    2016-01-01

    Massive injury remains the most common cause of death for productive age group globally. The current immune, inflammatory paradigm, based on an incomplete understanding of the functional integration of the complex host response, remains a major impediment to the development of effective innovative diagnostic and therapeutic effort. This study attempt to investigate the pattern of inflammatory and anti-inflammatory cytokines such as interleukin-6 and 10 (IL-6 and IL-10) and their interaction in severe injury condition with its major complication as multiple organ dysfunction syndrome (MODS) and failure (MOF) after polytrauma. This is multicenter study held at 4 academic Level-1 Trauma center included 54 polytrauma participants. Inclusion criteria were age between 16-60 years old, had new acute episode of polytrauma which defined as injury in ≥2 body region with Injury Severity Score (ISS) ≥16, and the presence of Systemic Inflammation Response Syndrome (SIRS). Serum level of IL-6 and IL-10 were taken on day 2, 3, and 5 after trauma. During hospitalization, samples were observed for the occurrence of MODS or MOF using Sequential Organ Failure Assessment (SOFA) and mortality rate were also noted. Participant were mostly male with mean of age of 35, 9 years old, endured polytrauma caused by traffic accident. Elevation of cytokines (IL-6, IL-10, and IL-6/IL-10 ratio) had directly proportional with MODS and mortality. Threshold level of compensation for severe trauma is IL-6 of 50 pg/mL and trauma load of ISS ≥30. Inflammation reaction greater than this threshold level would result in downhill level of IL-6, IL-10, or IL-6/IL-10 ratio which associated with poor outcome (MODS and death). The elevation of these cytokines level were represent as compensation/adaptive immune system and its fall represent decompensating/failure of immune system after severe trauma. The pattern of IL-6 and IL-10 after polytrauma represent immune system effort to restore homeostasis

  2. 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...

  3. 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

  4. Autocrine IL-6 mediates pituitary tumor senescence

    Science.gov (United States)

    Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K.; Arzt, Eduardo

    2017-01-01

    Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence. PMID:27902467

  5. Knocking out IL-6 by vaccination

    DEFF Research Database (Denmark)

    Galle, Pia; Hougs, Lotte; Barington, Torben

    2004-01-01

    Inappropriate expression of IL-6 plays a role in various inflammatory conditions, degenerative diseases, and cancers. Several model systems have been developed that can specifically block IL-6-receptor interactions. Here we present a simple and highly effective approach based on vaccination with ...

  6. IL-6 RESPONSES TO GLYCAEMIC INDEX DURING RECOVERY FROM EXERCISE

    Directory of Open Access Journals (Sweden)

    S.H. Hasani

    2015-06-01

    Full Text Available Purpose: This study examined the effect of meal with different glycaemic index (GI on plasma IL-6 concentration and glucose metabolism after maximal lengthening contractions of the knee extensors. Using a cross-over design, Material : 10 healthy males completed 5 sets of 10 lengthening (eccentric contractions at 120% 1 repetition-maximum. Subjects were randomized to consume the GI beverage (high-GI, low-GI (15% weight per volume; 3 g/kg BM or placebo in three times within 10 min following exercise, and again at 50 and 110 min during recovery time. Blood samples were collected before exercise and after 0.60, 180 min and 24 h of recovery. Results: Concentration of plasma IL-6 in HGI group was less than LGI and Pla groups. IL-6 tended to significantly increase after exercise in recovery time in 3 groups (all P < 0.05, except for 24 hours (P = 1.00, furthermore there was significant difference for IL-6 between placebo and high glycemic groups in 3hours after exercise (P=.016. Concentration of serum CK in HGI group was less than LGI and Pla groups, CK was significantly elevated at all times points during recovery in 3 groups (all P < 0.05, except for 1 hour after exercise in HGI group (P = 0.31, but there was no significant difference for CK between groups. Conclusion: In summary, consuming HGI carbohydrate during recovery from exercise attenuate plasma IL-6 concentration.

  7. Substantial elevation of interleukin-6 concentration in peritendinous tissue, in contrast to muscle, following prolonged exercise in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Olesen, Jens; Gemmer, Carsten

    2002-01-01

    Plasma interleukin-6 (IL-6) concentration has been shown to increase with exercise and various cell types and tissues have been suggested to be responsible for this increase. At present no studies have measured the interstitial concentration of IL-6 in skeletal muscle and connective tissue......, 48 h, 72 h and 96 h post-exercise in both the medial gastrocnemius muscle (not measured at rest due to risk of disabling the subsequent exercise, and 24 h and 72 h post-exercise) and the peritendinous tissue around the Achilles tendon using microdialysis catheters with a high molecular mass cut...

  8. Autonomy, Positive Relationships, and IL-6: Evidence for Gender-Specific Effects

    Science.gov (United States)

    Eisenlohr-Moul, Tory A.; Segerstrom, Suzanne C.

    2014-01-01

    Objectives A body of evidence indicates that women value relationship-centered aspects of well-being more than men do, while men value autonomy-centered aspects of well-being more than women do. The current study examined whether gender moderates relations between autonomy and positive relationships and interleukin-6 (IL-6), a cytokine associated with inflammatory processes. Aspects of well-being consistent with gender-linked values were expected to be most health-protective such that positive relationships would predict lower IL-6 only or more strongly in women, and autonomy would predict lower IL-6 only or more strongly in men. Methods In the first study, a sample of 119 older adults (55% female) living in Kentucky were visited in their homes for interviews and blood draws. In the second study, a sample of 1,028 adults (45% female) living across the United States (U.S.) underwent a telephone interview followed by a visit to a research center for blood draws. Results In the Kentucky sample, autonomy was quadratically related to IL-6 such that average autonomy predicted higher IL-6; this effect was stronger in men, providing support for our hypothesis only at above average levels of IL-6. In the U.S. national sample, more positive relationships were associated with lower IL-6 in women only. When the national sample was restricted to match the Kentucky sample, higher autonomy was associated with lower IL-6 in men only. Conclusions Results provide preliminary evidence for gender-specific effects of positive relationships and autonomy on IL-6. Further work is needed to establish the generalizability of these effects to different ages, cultures, and health statuses. PMID:22908985

  9. 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

  10. 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.

  11. Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

    DEFF Research Database (Denmark)

    Galle, Pia; Jensen, Lene; Andersson, Christina

    2007-01-01

    ; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental...

  12. Polymorphisms of the interleukin-6 gene promoter and abdominal aortic aneurysm.

    Science.gov (United States)

    Smallwood, L; Allcock, R; van Bockxmeer, F; Warrington, N; Palmer, L J; Iacopetta, B; Norman, P E

    2008-01-01

    Elevated levels of circulating interleukin-6 (IL-6) have been reported in patients with abdominal aortic aneurysms (AAAs). Although this implicates inflammation as a cause of AAAs, there is also evidence that the aneurysmal aorta may secrete IL-6 into the circulation as a result of aortic proteolysis. Genetic association studies are one means of trying to clarify the role of specific mediators in the causal pathway. The aim of the present study was to examine the association between variants of the IL-6 gene and AAAs. An association study involving 677 men with screen-detected AAAs and 656 age-matched controls was performed. Three variants in the IL-6 promoter region were analysed: IL-6-174G>C (rs1800795), IL-6-572G>C (rs1800796) and IL-6-597G>A (rs1800797). Univariate regression of SNP genotype on AAA as a binary outcome was initially performed under a range of genetic models (additive, dominant and recessive). This was followed by multivariate analyses, testing the same models but including risk factors known to be associated with AAAs. All analyses and haplotype estimation were performed under a generalized linear model framework. IL-6-572G>C polymorphism (frequency 1.5% in cases) was identified as an independent risk factor for AAA with an odds ratio (OR) of 6.00 (95%CI: 1.22, 29.41) when applied to the recessive model. No association was seen in the additive or dominant models. In a multivariate analysis using the most common haplotype (h.111, frequency 48.7%) as a reference, h.211 (frequency 4.4%) was an independent risk factor for AAA (OR 1.56, 95%CI: 1.02, 2.39). The IL-6 572G>C polymorphism (and h.211 haplotype) is associated with AAA, however it is too rare to be an important cause of most AAAs. This does not support the concept that the elevated level of IL-6 reported in patients with AAAs is a primary cause of the aneurysmal process.

  13. 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

  14. Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions.

    Science.gov (United States)

    Zhou, Jing; Jin, Jun-O; Patel, Ekta S; Yu, Qing

    2015-12-01

    Interleukin (IL)-6 is a multi-functional cytokine that can either promote or suppress tissue inflammation depending on the specific disease context. IL-6 is elevated in the exocrine glands and serum of patients with Sjögren's syndrome (SS), but the specific role of IL-6 in the pathogenesis of this disease has not been defined. In this study, we showed that IL-6 expression levels were increased with age in C56BL/6.NOD-Aec1Aec2 mice, a primary SS model, and higher than the control C57BL/6 mice. To assess the role of IL-6 during the immunological phase of SS development, a neutralizing anti-IL-6 antibody was administered into 16 week-old female C56BL/6.NOD-Aec1Aec2 mice, 3 times weekly for a consecutive 8 weeks. Neutralization of endogenous IL-6 throughout the immunological phase of SS development led to increased apoptosis, caspase-3 activation, leukocytic infiltration, and IFN-γ- and TNF-α production in the salivary gland. To further determine the effect of IL-6 on the apoptosis of exocrine gland cells, recombinant human IL-6 or the neutralizing anti-IL-6 antibody was injected into female C57BL/6 mice that received concurrent injection of anti-CD3 antibody to induce the apoptosis of exocrine gland tissues. Neutralization of IL-6 enhanced, whereas administration of IL-6 inhibited apoptosis and caspase-3 activation in salivary and lacrimal glands in this model. The apoptosis-suppressing effect of IL-6 was associated with up-regulation of Bcl-xL and Mcl-1 in both glands. Moreover, IL-6 treatment induced activation of STAT3 and up-regulated Bcl-xL and Mcl-1 gene expression in a human salivary gland epithelial cell line. In conclusion, IL-6 inhibits the apoptosis of exocrine gland tissues and exerts a tissue-protective effect under inflammatory conditions including SS. These findings suggest the possibility of using this property of IL-6 to preserve exocrine gland tissue integrity and function under autoimmune and inflammatory conditions. Copyright © 2015 Elsevier

  15. Increase in interleukin-6 immediately after wheelchair basketball games in persons with spinal cord injury: preliminary report.

    Science.gov (United States)

    Kinoshita, T; Nakamura, T; Umemoto, Y; Kojima, D; Moriki, T; Mitsui, T; Goto, M; Ishida, Y; Tajima, F

    2013-06-01

    Case series. To investigate the effects of wheelchair basketball game on plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and blood cell counts in persons with spinal cord injury (SCI). The 2009 Mei-shin League of Wheelchair Basketball Games held at Wakayama, Japan. Five wheelchair basketball players with SCI voluntarily participated in this study. Blood samples were taken approximately 1 h before the player warm-up for the game and immediately after the game. IL-6, TNF-α, CRP and blood cell count were measured. Plasma IL-6 level and number of monocytes were significantly increased after the game, compared with pre-game measurements (P<0.05). No changes were observed in other measurements. There was a significant relationship between increased IL-6 levels and accumulated play duration. The lack of change in TNF-α and CRP levels suggested that the exercise-induced rise in IL-6 was not related to exercise-induced inflammatory response. Furthermore, the associated increase in the number of monocytes did not correlate with exercise-induced IL-6 changes, negating monocytes as the source of IL-6.

  16. 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.

  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. Attenuated lung fibrosis in interleukin 6 knock-out mice after C-ion irradiation to lung

    International Nuclear Information System (INIS)

    Saito-Fujita, Tomoko; Iwakawa, Mayumi; Nakamura, Etsuko; Nakawatari, Miyako; Fujita, Hidetoshi; Moritake, Takashi; Imai, Takashi

    2011-01-01

    There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice. The mice underwent thoracic irradiation with 10 Gy of C-ion beam or sham-irradiation and were examined by histology. Immunoreactivity for IL-6 was induced at the site of bronchiolar epithelium, in pneumocytes and in monocytes by C-ion irradiation. At 24 weeks after irradiation, the infiltration of macrophages, detected by positive immunohistological staining with Mac3 antibody, was observed in alveolar spaces both in WT and IL-6 KO mice. The thickening of bronchiolar and alveolar walls exhibited in WT mice, but not KO mice, and fibrotic changes detected by Masson-Trichrome staining, were observed only in the lungs of WT mice, while it was attenuated in IL-6 KO mice. These results indicated that IL-6 might not be essential for activating macrophages in the late phase, but plays an important role for fibrotic changes of the alveolar wall after irradiation. (author)

  19. 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

  20. CGI-99 promotes breast cancer metastasis via autocrine interleukin-6 signaling.

    Science.gov (United States)

    Lin, C; Liao, W; Jian, Y; Peng, Y; Zhang, X; Ye, L; Cui, Y; Wang, B; Wu, X; Xiong, Z; Wu, S; Li, J; Wang, X; Song, L

    2017-06-29

    Metastatic relapse remains largely incurable and a major challenge of clinical management in breast cancer, but the underlying mechanisms are poorly understood. Herein, we report that CGI-99 is overexpressed in breast cancer tissues from patients with metastatic recurrence within 5 years. High CGI-99 significantly predicts poorer 5-year metastasis-free patient survival. We find that CGI-99 increases breast cancer stem cell properties, and potentiates efficient tumor lung colonization and outgrowth in vivo. Furthermore, we demonstrate that CGI-99 activates the autocrine interleukin-6 (IL-6)/STAT3 signaling by increasing the accumulation and activity of RNA polymerase II and p300 cofactor at the proximal promoter of IL-6. Importantly, delivery of the IL-6-receptor humanized monoclonal antibody tocilizumab robustly abrogates CGI-99-induced metastasis in vivo. Finally, we find that high levels of CGI-99 are significantly correlated with STAT3 hyperactivation in breast cancer patients. These findings reveal a potential mechanism for constitutive activation of autocrine IL-6/STAT3 signaling and may suggest a novel target for clinical intervention in breast cancer.

  1. 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.

  2. Detection and characterization of interleukin-6 gene variants in Canis familiaris: association studies with periodontal disease.

    Science.gov (United States)

    Morinha, Francisco; Albuquerque, Carlos; Requicha, João; Dias, Isabel; Leitão, José; Gut, Ivo; Guedes-Pinto, Henrique; Viegas, Carlos; Bastos, Estela

    2011-10-10

    Periodontal disease (PD) is the most common inflammatory disease of the oral cavity of domestic carnivores. In Human Medicine molecular genetics research showed that several genes play a role in the predisposition and progression of this complex disease, primarily through the regulation of inflammatory mediators, but the exactly mechanisms are poorly understood. This study aims to contribute to the characterization of the genetic basis of PD in the dog, a classically accepted model in Periodontology. We searched for genetic variations in the interleukin-6 (IL6) gene, in order to verify its association with PD in a case-control study including 25 dogs in the PD case group and 45 dogs in the control group. We indentified and characterized three new genetic variations in IL6 gene. No statistically significant differences were detected between the control and PD cases groups. Our results do not support an evidence for a major role contribution of these variants in the susceptibility to PD in the analyzed population. Nevertheless, the sequence variant I/5_g.105G>A leads to an amino acid change (arginine to glutamine) and was predicted to be possibly damaging to the IL6 protein. A larger cohort and functional studies would be of extreme importance in a near future to understand the possible role of IL6 variants in this disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Significance of Interleukin-6 Signaling in the Resistance of Pharyngeal Cancer to Irradiation and the Epidermal Growth Factor Receptor Inhibitor

    International Nuclear Information System (INIS)

    Chen, C.-C.; Chen, W.-C.; Lu, C.-H.; Wang, W.-H.; Lin, P.-Y.; Lee, K.-D.; Chen, M.-F.

    2010-01-01

    Purpose: Tumor eradication by chemoradiotherapy for pharyngeal cancer has not been particularly successful. Targeting epithelial growth factor receptor (EGFR) could be a potential treatment strategy providing additional benefits, but only a subset of these tumors gives a clinically significant response to EGFR inhibitors. The aim has been to identify the role of interleukin-6 (IL-6) signaling and its predictive power in the treatment response of pharyngeal cancer. Methods and Materials: Human pharyngeal cancer cell lines, including the hypopharyngeal cancer cell line FaDu and its derived cell line FaDu-C225-R, were selected. Changes in tumor growth, response to treatment, and responsible signaling pathway were investigated in vitro. Furthermore, 95 pharyngeal cancer tissue specimens were analyzed by immunohistochemical staining, and correlations were made between levels of IL-6, IL-6 receptor (IL-6R), p-AKT, and p-STAT3 expression and the clinical outcome of patients. Results: In vitro, either extrinsic IL-6 stimulation of cancer cells or intrinsically activated IL-6 signaling detected in FADu-C225-R cells results in resistance to irradiation and EGFR inhibitor. Blocking IL-6 signaling attenuated aggressive tumor behavior and sensitized the cells to treatments. The responsible mechanisms included decreased p-STAT3, less nuclear translocation of EGFR, and subsequently attenuated epithelial-mesenchymal transition. Regarding clinical data, staining of p-STAT3 and IL-6 was significantly linked with lower response rates to treatments and shorter survival in pharyngeal cancer patients. Conclusions: IL-6 and p-STAT3 may be significant predictors of pharyngeal carcinoma, and regulating IL-6 signaling can be considered a promising therapeutic approach.

  4. Interleukin-6 as an endogenous pyrogen: induction of prostaglandin E2 in brain but not in peripheral blood mononuclear cells.

    Science.gov (United States)

    Dinarello, C A; Cannon, J G; Mancilla, J; Bishai, I; Lees, J; Coceani, F

    1991-10-25

    Fever induced by endogenous as well as exogenous pyrogens is often prevented by cyclooxygenase inhibitors; endogenous pyrogens stimulate prostaglandin E2 (PGE2) in or near the thermoregulatory centers of the brain. The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), are two pyrogens which stimulate brain PGE2 formation during fever and also increase PGE2 synthesis in human mononuclear cells in vitro. In the present study, we examined whether interleukin-6 (IL-6) stimulates PGE2 formation in a manner similar to IL-1 and TNF. Both glycosylated and non-glycosylated forms of recombinant human IL-6 were tested. Following intravenous injection into rabbits, the glycosylated IL-6 was more pyrogenic than the non-glycosylated form and there was no evidence of synergy in the production of fever when IL-6 and IL-1 were given simultaneously. IL-6 fever was blocked by prior administration of the cyclooxygenase inhibitor ibuprofen. IL-6 was also pyrogenic in the cat by either the systemic or the intraventricular route. However, in both species, IL-6 was less effective than IL-1 beta. When given intraventricularly to cats, IL-6 produced an increase in PGE2 levels of the cerebrospinal fluid in parallel with the rise in body temperature. In the latter respect, IL-6 imitated IL-1 beta; however, IL-6 from 0.15-15 micrograms/ml did not increase mononuclear cell PGE2 production in vitro whereas IL-1 beta induced 20-30-fold increases in PGE2 at 100 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Interleukin-6 levels in the central nervous system are negatively correlated with fat mass in overweight/obese subjects.

    Science.gov (United States)

    Stenlöf, Kaj; Wernstedt, Ingrid; Fjällman, Ted; Wallenius, Ville; Wallenius, Kristina; Jansson, John-Olov

    2003-09-01

    Recently, we demonstrated that intracerebroventricular injection of IL-6 increases energy expenditure and decreases body fat in rodents. Therefore, IL-6 may play a role in appetite and body weight control in the central nervous system. In the present study we evaluated cerebrospinal fluid (CSF) and serum IL-6 levels in humans in relation to body fat content and to CSF and serum levels of leptin. Thirty-two healthy overweight/obese male subjects with a body mass index range of 29.3-36.0 kg/m(2) were studied. Total and sc body fat were measured by dual energy x-ray absorptiometry and computed tomography, respectively. CSF IL-6 levels were in some individuals higher than serum IL-6 levels and correlated negatively with total body weight, sc and total body fat. In contrast, CSF leptin levels were 30-60 times lower than serum leptin levels and correlated positively with serum leptin, body weight, sc and total body fat. Furthermore, there was a negative correlation between CSF IL-6 and leptin. In conclusion, CSF IL-6 differs in many ways from CSF leptin. CSF IL-6 may be locally produced rather than serum derived, and body fat-regulating regions in the central nervous system may be exposed to insufficient IL-6 levels in more severe obesity.

  6. Predictive value of interleukin-6 in post-cardiac arrest patients treated with targeted temperature management at 33 °C or 36 °C

    DEFF Research Database (Denmark)

    Bro-Jeppesen, John; Kjaergaard, Jesper; Stammet, Pascal

    2016-01-01

    AIM: Post-cardiac arrest syndrome (PCAS) is characterized by systemic inflammation, however data on the prognostic value of inflammatory markers is sparse. We sought to investigate the importance of systemic inflammation, assessed by interleukin-6 (IL-6) in comatose survivors of out-of-hospital c...

  7. 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...

  8. 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 ...

  9. 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...

  10. The role of IL-6 in exercise-induced anorexia in normal-weight boys.

    Science.gov (United States)

    Hunschede, Sascha; Schwartz, Alexander; Kubant, Ruslan; Thomas, Scott G; Anderson, G Harvey

    2018-03-28

    Our previous study showed that Interleukin-6 (IL-6) is associated with a suppression of appetite after high-intensity exercise (HIEX), but an independent role within food intake (FI) was not defined. IL-6 after HIEX (75% VO2peak) is independent of appetite-hormones in suppressing appetite and FI in normal-weight (NW) boys. To investigate the effect of HIEX, with and without the inflammation inhibitor, ibuprofen (IBU), on IL-6 and selective biomarkers of inflammation and appetite on FI and ratings of appetite in NW boys. Fifteen NW boys (aged 13-18y) were randomly assigned in a crossover design to four sessions: 1)Water+Rest; 2)Rest+IBU; 3)Water+HIEX; 4)HIEX+IBU. HIEX consisted of three 10min bouts of HIEX at 60-70RPM75% VO2max with 1:30min active rest interposed. IBU was given in a 300mg liquid solution. EI, ratings and plasma biomarkers of appetite, inflammation, stress and glucose control were measured. FI was not affected by HIEX or IBU. Appetite increased over TIME (p=0.002) but was lower after HIEX (p<0.001) with no effect of IBU. HIEX, but not IBU, also resulted in higher levels of IL-6 (p<0.001) and cortisol (P<0.001), and lower active ghrelin (P<0.001). IL-6 correlated with active ghrelin (r=0.37; p=0.036) and Cortisol (r=0.26; p=0.049). HIEX reduces subjective appetite but not EI, accompanied by an increase of IL-6 and cortisol and a decrease of active ghrelin and blood glucose. An independent role for IL-6 in appetite suppression was not supported. However, IL-6 was associated with active ghrelin and cortisol, thus potentially mediating appetite via these interactions.

  11. Increased Level of Interleukin 6 Associates With Increased 90-Day and 1-Year Mortality in Patients With End-Stage Liver Disease.

    Science.gov (United States)

    Remmler, Johannes; Schneider, Christoph; Treuner-Kaueroff, Theresa; Bartels, Michael; Seehofer, Daniel; Scholz, Markus; Berg, Thomas; Kaiser, Thorsten

    2018-05-01

    Organ allocation for liver transplantation is based on prognosis, using the model for end-stage liver disease (MELD) or MELD including serum sodium (MELD-Na) score. These scores do not consider systemic inflammation and septic complications. Blood level of C-reactive protein (CRP), in addition to the MELD score, associates with mortality in patients with end-stage liver disease, whereas levels of interleukin 6 (IL6) have not been systematically studied. We performed a retrospective observational cohort study of 474 patients with end-stage liver disease (63.5% male; median age, 56.9 years), evaluated for liver transplantation in Germany, with at least 1 year of follow up. Data were collected on blood levels of CRP, IL6, and white blood cell count (WBC). Findings were analyzed in relation to mortality and compared with patients' MELD scores and MELD-Na scores. For survival analysis, the cohort was divided into quartiles of IL6, CRP, and WBC levels, as well as MELD scores. Log-rank test and the Cox proportional hazards regression model were used to compare the groups, and area under the receiver operating characteristic (AUROC) values were calculated. Blood levels of IL6 and MELD scores associated with mortality: none of the patients with levels of IL6 below the first quartile (below 5.3 pg/mL) died within 1 year. In contrast, 67.7% of the patients in the highest quartile of IL6 level (37.0 pg/mL or more) died within 1 year. MELD score also correlated with mortality: among patients with MELD scores below 8.7, 0.9% died within 1 year, whereas in patients with MELD scores of 18.0 or more, 67.4% died within 1 year. The predictive value of level of IL6 (AUROC, 0.940) was higher than level of CRP (AUROC, 0.866) (P = .009) or WBC (AUROC, 0.773) (P Level of IL6 associated with 1-year mortality (AUROC, 0.916) to a greater extent than liver synthesis or detoxification markers international normalized ratio (AUROC, 0.839) (P = .007) or bilirubin (AUROC 0.846) (P = .007

  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. The impact of anxiety and catastrophizing on interleukin-6 responses to acute painful stress

    Directory of Open Access Journals (Sweden)

    Lazaridou A

    2018-03-01

    Full Text Available Asimina Lazaridou,1 Marc O Martel,1 Christine M Cahalan,1 Marise C Cornelius,1 Olivia Franceschelli,1 Claudia M Campbell,2 Jennifer A Haythornthwaite,2 Michael Smith,2 Joseph Riley,3 Robert R Edwards1 1Department of Anesthesiology, Harvard Medical School, Brigham & Women’s Hospital, Boston, MA, USA; 2Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; 3Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville, FL, USA Objective: To examine the influence of anxiety and pain-related catastrophizing on the time course of acute interleukin-6 (IL-6 responses to standardized noxious stimulation among patients with chronic pain.Methods: Data were collected from 48 participants in the following demographically matched groups: patients with chronic pain (n=36 and healthy controls (n=12. Participants underwent a series of Quantitative Sensory Testing (QST procedures assessing responses to mechanical and thermal stimuli during two separate visits, in a randomized order. One visit consisted of standard, moderately painful QST procedures, while the other visit involved nonpainful analogs to these testing procedures. Blood samples were taken at baseline, and then for up to 2 hours after QST in order to study the time course of IL-6 responses.Results: Results of multilevel analyses revealed that IL-6 responses increased across assessment time points in both visits (p<0.001. While patients with chronic pain and healthy controls did not differ in the magnitude of IL-6 responses, psychological factors influenced IL-6 trajectories only in the chronic pain group. Among patients, increases in catastrophizing over the course of the QST session were associated with elevated IL-6 responses only during the painful QST session (p<0.05. When controlling for anxiety, results indicated that the main multilevel model among patients remained significant

  14. Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin-6 dependent.

    Science.gov (United States)

    Reddel, C J; Allen, J D; Ehteda, A; Taylor, R; Chen, V M Y; Curnow, J L; Kritharides, L; Robertson, G

    2017-03-01

    Essentials Cancer cachexia and cancer-associated thrombosis have not previously been mechanistically linked. We assessed thrombin generation and coagulation parameters in cachectic C26 tumor-bearing mice. C26 mice are hypercoagulable, partially corrected by blocking tumor derived interleukin-6. Coagulability and anti-inflammatory interventions may be clinically important in cancer cachexia. Background Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer, which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. Objectives To assess if cancer cachexia altered the coagulation state and if this was attributable to tumor IL-6 production. Methods In male BALB/c*DBA2 (F1 hybrid) mice with a C26 tumor we used modified calibrated automated thrombogram and fibrin generation (based on overall hemostatic potential) assays to assess the functional coagulation state, and also examined fibrinogen, erythrocyte sedimentation rate (ESR), platelet count, tissue factor pathway inhibitor (TFPI) and hepatic expression of coagulation factors by microarray. C26 mice were compared with non-cachectic NC26, pair-fed and sham control mice. IL-6 expression in C26 cells was knocked down by lentiviral shRNA constructs. Results C26 mice with significant weight loss and highly elevated IL-6 had elevated thrombin generation, fibrinogen, ESR, platelets and TFPI compared with all control groups. Fibrin generation was elevated compared with pair-fed and sham controls but not compared with NC26 tumor mice. Hepatic expression of coagulation factors and fibrinolytic inhibitors was increased. Silencing IL-6 in the tumor significantly, but incompletely, attenuated the increased thrombin generation, fibrinogen and TFPI. Conclusions Cachectic C26 tumor-bearing mice are in a

  15. 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...

  16. Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content

    DEFF Research Database (Denmark)

    Steensberg, A; Febbraio, M A; Osada, T

    2001-01-01

    1. Prolonged exercise results in a progressive decline in glycogen content and a concomitant increase in the release of the cytokine interleukin-6 (IL-6) from contracting muscle. This study tests the hypothesis that the exercise-induced IL-6 release from contracting muscle is linked to the intram......1. Prolonged exercise results in a progressive decline in glycogen content and a concomitant increase in the release of the cytokine interleukin-6 (IL-6) from contracting muscle. This study tests the hypothesis that the exercise-induced IL-6 release from contracting muscle is linked...... to the intramuscular glycogen availability. 2. Seven men performed 5 h of a two-legged knee-extensor exercise, with one leg with normal, and one leg with reduced, muscle glycogen content. Muscle biopsies were obtained before (pre-ex), immediately after (end-ex) and 3 h into recovery (3 h rec) from exercise in both...... legs. In addition, catheters were placed in one femoral artery and both femoral veins and blood was sampled from these catheters prior to exercise and at 1 h intervals during exercise and into recovery. 3. Pre-exercise glycogen content was lower in the glycogen-depleted leg compared with the control...

  17. Plasma cytokine IL-6 levels and subjective cognitive decline: preliminary findings.

    Science.gov (United States)

    Keegan, Andrew P; Paris, Daniel; Luis, Cheryl A; Abdullah, Laila; Ait-Ghezala, Ghania; Beaulieu-Abdelahad, David; Pryor, Makenzie; Chaykin, Jillian; Crynen, Gogce; Crawford, Fiona; Mullan, Michael

    2018-02-01

    Detection of Alzheimer's disease (AD) prior to clinical inception will be paramount for introducing disease modifying treatments. We have begun collecting baseline characteristics of a community cohort for longitudinal assessment and testing of antecedent blood-based biomarkers. We describe the baseline visit from the first 131 subjects in relationship to a commonly described cytokine, interleukin 6 (IL-6). Subjects from the community presented for a free memory screening with varying degrees of memory concern. We quantified the baseline plasma levels of the cytokine IL-6 and assessed cognition (Montreal Cognitive Assessment, MoCA) and mood (Geriatric Depression Scale, GDS) in relationship to their memory concern. Baseline MoCA scores were inversely related to age, and this association was influenced by an AD risk factor, Apolipoprotein E (APOE4) carrier status. The degree of subjective cognitive decline correlated with GDS and was inversely related to MoCA scores. Interleukin 6 levels were related to age, body mass index, and years of education. It will be important to assess how these baseline IL-6 levels and forthcoming novel biomarkers relate to future cognitive decline. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  18. HER2 overexpression elicits a proinflammatory IL-6 autocrine signaling loop that is critical for tumorigenesis.

    Science.gov (United States)

    Hartman, Zachary C; Yang, Xiao-Yi; Glass, Oliver; Lei, Gangjun; Osada, Takuya; Dave, Sandeep S; Morse, Michael A; Clay, Timothy M; Lyerly, Herbert K

    2011-07-01

    HER2 overexpression occurs in approximately 25% of breast cancers, where it correlates with poor prognosis. Likewise, systemic inflammation in breast cancer correlates with poor prognosis, although the process is not understood. In this study, we explored the relationship between HER2 and inflammation, comparing the effects of overexpressing wild-type or mutated inactive forms of HER2 in primary human breast cells. Wild-type HER2 elicited a profound transcriptional inflammatory profile, including marked elevation of interleukin-6 (IL-6) expression, which we established to be a critical determinant of HER2 oncogenesis. Mechanistic investigations revealed that IL-6 secretion induced by HER2 overexpression activated Stat3 and altered gene expression, enforcing an autocrine loop of IL-6/Stat3 expression. Both mouse and human in vivo models of HER2-amplified breast carcinoma relied critically on this HER2-IL-6-Stat3 signaling pathway. Our studies offer the first direct evidence linking HER2 to a systemic inflammatory mechanism that orchestrates HER2-mediated tumor growth. We suggest that the HER2-IL-6-STAT3 signaling axis we have defined in breast cancer could prompt new therapeutic or prevention strategies for treatment of HER2-amplified cancers. ©2011 AACR.

  19. Short-term acetaminophen consumption enhances the exercise-induced increase in Achilles peritendinous IL-6 in humans

    DEFF Research Database (Denmark)

    Gump, Brian S; McMullan, David R; Cauthon, David J

    2013-01-01

    Through an unknown mechanism the cyclooxygenase (COX) inhibitor acetaminophen (APAP) alters tendon mechanical properties in humans when consumed during exercise. Interleukin-6 (IL-6) is produced by tendon during exercise and is a potent stimulator of collagen synthesis. In non-tendon tissue, IL-6...... is upregulated in presence of COX-inhibitors and may contribute to alterations in extracellular matrix turnover, possibly due to inhibition of prostaglandin E2 (PGE2). We evaluated the effects of APAP on IL-6 and PGE2 in human Achilles peritendinous tissue after 1-hour of treadmill exercise. Subjects were...... randomly assigned to a placebo (n=8, 26±1 y) or APAP (n=8, 25±1 y) group. Each subject completed a non-exercise and exercise experiment consisting of 6-hours of microdialysis. Drug (APAP, 1000 mg) or placebo was administered in a double-blind manner during both experiments. PGE2 and IL-6 were determined...

  20. [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.

  1. The interleukin-6 (-174) G/C promoter polymorphism is associated with type-2 diabetes mellitus in Native Americans and Caucasians

    DEFF Research Database (Denmark)

    Vozarova, Barbora; Fernández-Real, José-Manuel; Knowler, William C

    2003-01-01

    Chronic low-grade activation of the immune system may play a role in the pathogenesis of type-2 diabetes mellitus (T2DM). Interleukin-6 (IL6), a powerful inducer of hepatic acute phase response, has been implicated in the etiology of insulin resistance and T2DM. Recently, an IL6 promoter...... polymorphism (G/C) at position -174 was found to be associated with measures of insulin sensitivity. Because we have previously found an association between high IL6 levels and insulin resistance in both Pima Indians - a population with high rates of insulin resistance and T2DM - and Caucasians, we aimed...... to assess whether the IL6 promoter polymorphism is associated with T2DM in these populations. We genotyped the IL6 (-174) G/C polymorphism using pyrosequencing in 463 Native Americans and by PCR-RFLP in 329 Spanish Caucasians. Among the Spanish Caucasian subjects, there was a significant difference...

  2. Analysis of polymorphisms in the promoter region and protein levels of interleukin-6 gene among gout patients.

    Science.gov (United States)

    Tsai, P-C; Chen, C-J; Lai, H-M; Chang, S-J

    2008-01-01

    To explore the associations between the polymorphisms and protein levels of interleukin-6 (IL-6) gene and gout disease. A total of 120 male gout patients and 184 healthy controls were enrolled. Each patient was matched with 1-2 gout-free controls by age within three years. Four polymorphisms in the promoter of IL-6 gene, including -597G/A, -572C/G, -373A(m)T(n), and -174G/C, and the IL-6 levels were analyzed. The clinical characteristics and biochemical markers in plasma were measured, including age of gout onset, duration of gout history, tophus number, gout attack frequency, uric acid, total cholesterol, triglycerides and creatinine. The mean IL-6 level for gout patients was 9.80 (+/-11.76 pg/ml) which showed no significant difference from the controls (7.06+/-7.58 pg/ml, p=0.230). When the IL-6 levels were dichotomized according to the median value (5 pg/ml), there were significantly higher proportions of the gout patients (59.66%) than controls (44%) with high IL-6 levels (OR=1.88, 95% CI=1.17-3.02, p=0.008). Unique genotype was found at polymorphisms -174G/C and -597G/A. Neither the polymorphisms -572C/G nor -373A(m)T(n) in the genotype or allele distributions showed a significant association related to clinical characteristics, biochemical markers, IL-6 levels or gout disease (all p>0.05). Those with gout disease have greater proportions of high IL-6 levels in plasma than controls, and there is no significant association between the four polymorphisms in the promoter region of IL-6 gene and gout disease.

  3. Serum concentrations of chemokines (CCL-5 and CXCL-12), chemokine receptors (CCR-5 and CXCR-4), and IL-6 in patients with posttraumatic stress disorder and avoidant personality disorder.

    Science.gov (United States)

    Ogłodek, Ewa A; Szota, Anna M; Moś, Danuta M; Araszkiewicz, Aleksander; Szromek, Adam R

    2015-12-01

    Posttraumatic stress disorder (PTSD) can be perceived as a psychoneuroimmunological disorder in which cytokines affecting the neurochemical and neuroendocrine functions of the body play an important role. Among cytokines, chemokines participating in activation of the inflammatory response are considered to be crucial. 220 men and women were enrolled in the study. 180 of them constituted the study group. The studied groups consisted of: 60 patients with a diagnosed avoidant personality disorders (APD), 60 patients with a diagnosed APD and with PTSD and of 60 patients with PTSD but without a APD. There were 30 women and 30 men in each group of 60 subjects. The control group consisted of 40 healthy individuals. The plasma levels of chemokines and their receptors (CCL-5, CXCR-5, CXCL-12 and CXCR-4), as well as IL-6, were assessed by ELISA. There was an increase in the CXCL-12 and CCL-5 levels in women and men with the PTSD versus the control group. Also, increased levels of IL-6 and the receptors CXCR-4, CCR-5 were observed in women and men with PTSD. The levels of CXCL-12 and CCL-5 chemokines, as well as CCR-5 and CXCR4 receptors were higher in women than in men. The results of this study indicate a need for assessment of the CCL-5 and CXCL-12 chemokine levels, as they are likely markers of PTSD. Measurement of the concentrations of chemokines, chemokine receptors and IL-6 in women and men with PTSD along with concomittant APD may be useful for early detection of mental disorders. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. The effects of IL-6 and its receptors on bone loss in postmenopausal women

    International Nuclear Information System (INIS)

    Huang Xin; Yang Weiwen; Zhang Xueguang

    2001-01-01

    Objective: To investigate the effects of IL-6 and its receptors on bone loss in healthy women, and to assess the pathogenesis of the postmenopausal osteoporosis in women. Methods: One hundred and thirty one healthy women aged 31-72 including 64 sexual maturity women aged 31-52 were enrolled in four groups and 67 postmenopausal women, the years of menopause from 1 month to 23 years, were also enrolled in four groups. The bone mass of the lumbar-spine and femur were measured using dual-energy X-rays absorptiometry; the serum E 2 , FSH, BGP by radioimmunoassay (RIA); the serum IL-6, sIL-6R, sgp 130 by ELISA; the serum AKP, calcium, phosphate by auto-biochemistry instrument. Results: The BMD of lumbar-spine and right femur decreased following increase of age and the duration of menopause. Significant positive correlation was observed between BMD and E 2 . The serum IL-6, sIL-6R, sgp 130 level was low, and stable before menopause. The level of IL-6, sIL-6R, sgp 130 increased with variation of age and the duration of menopause. Significant negative correlation was observed between IL-6, sIL-6R, sgp 130 and E 2 , BMD. Serum AKP and BGP level was higher in postmenopausal women than that in sexual maturity women. The serum calcium level increased significantly soon after menopausal, then decreased to the normal level. The serum phosphate level had no difference in these groups. Conclusion: The main cause of postmenopausal osteoporosis is the unbalance of the bone formation and resorption

  5. [Effects of prophylactic antibiotic agent on interleukin-6 level in open chest surgery--comparison between imipenem and flomoxef].

    Science.gov (United States)

    Sohma, A; Kitaura, K; Toda, S; Satoh, S; Wada, Y; Yamagishi, H; Oka, T; Fujita, N

    1998-09-01

    Cytokines are known to increase in the patients subjected to open chest surgery. Those patients are usually administered with antibiotic agents for prophylaxis, while some of antibiotic agents might yield significantly higher level of cytokines than other agents especially in patients suffering from severe infections. It is believed that imipenem may yield lower interleukin-6 (IL6) level than cephem antibiotics. To study whether such difference could be observed in the patients who show no sign of severe infections, a total of 13 patients underwent scheduled open chest surgery were allocated at random into two groups, the imipenem-group and the flomoxef-group. The cytokine levels of the patients in the two groups were compared, while the prophylactic administration of imipenem or flomoxef. In both groups, IL6 increased immediately after the operation while endotoxin remained unchanged. Thereafter IL6 decreased gradually in both groups, however, the decrease of IL6 in the imipenem-group was faster and greater than the flomoxef-group resulting in the significantly lower level of IL6 on the 4th day after operation. One week after the operation, there existed no difference in the IL6 levels between these two groups. In conclusion, it was suggested that, depending on the choice of a prophylactic antibiotic agent, some invasive burden could be added to those patients underwent open chest surgery, a certain number of whom would develop severe infection.

  6. Can perioperative C-reactive protein and interleukin-6 levels predict atrial fibrillation after coronary artery bypass surgery?

    International Nuclear Information System (INIS)

    Ziabaksh-Tabari, S.

    2008-01-01

    Objective was to examine the relationship between proinflammatory cytokines such as interleukin-6 (IL-6) and C-reactive protein (CRP) and atrial fibrillation and after on-pump coronary artery bypass grafting (CABG). Fifty-four patients with coronary artery disease undergoing elective CABG at the Mazandaran Medical University, Mazandaran, Iran were enrolled in our prospective study in the year 2007. Postoperatively, heart rate and rhythm were continuously monitored for 5 days. Fasting blood samples were taken from all patients to examine quantities of CRP and IL-6 the day before surgery and on the second postoperative day in the intensive care unit. From 54 patients, 11 patients (20.4%) developed atrial fibrillation (AF) after CABG. The median age of patients with AF was 51.45+/-10.74 compared with 57.28+/-9.04 for patients with sinus rhythm (p=0.072). Cardioplegic time, cross clamp time and pump time were higher in the AF group but there was no significant difference between the 2 groups. Preoperative CRP and IL-6 levels were higher in patients with AF. The CRP and IL-6 increased after CABG in all patients but it increased more in the AF group. There was a significant relationship between preoperative IL-6 and AF in patients who underwent on-pump CABG, but there was no relationship between CRP and AF. Therefore, administration of glucocordicoids which significantly reduce plasma levels of IL-6 can reduce the incidence of AF after on-pump CABG. (author)

  7. 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.

  8. Autonomy, positive relationships, and IL-6: evidence for gender-specific effects.

    Science.gov (United States)

    Eisenlohr-Moul, Tory; Segerstrom, Suzanne

    2013-05-01

    A body of evidence indicates that women value relationship-centred aspects of well-being more than men do, while men value autonomy-centred aspects of well-being more than women do. The current study examined whether gender moderates relations between autonomy and positive relationships and interleukin-6 (IL-6), a cytokine associated with inflammatory processes. Aspects of well-being consistent with gender-linked values were expected to be most health protective such that positive relationships would predict lower IL-6 only or more strongly in women, and autonomy would predict lower IL-6 only or more strongly in men. In the first study, a sample of 119 older adults (55% female) living in Kentucky were visited in their homes for interviews and blood draws. In the second study, a sample of 1,028 adults (45% female) living across the United States underwent a telephone interview followed by a visit to a research centre for blood draws. In the Kentucky sample, autonomy was quadratically related to IL-6 such that moderate autonomy predicted higher IL-6; this effect was stronger in men. In the US national sample, more positive relationships were associated with lower IL-6 in women only. When the national sample was restricted to match the Kentucky sample, moderate autonomy was again associated with higher IL-6 in men only. Results provide preliminary evidence for gender-specific effects of positive relationships and autonomy on IL-6. Further work is needed to establish the generalizability of these effects to different ages, cultures, and health statuses. What is already known on this subject? A host of previous work indicates that women value relationship-centred aspects of well-being more than men, while men value autonomy-centred aspects of well-being more than women. Further, there is some evidence suggesting that well-being consistent with gender-linked values is more health protective, such that relationships are more protective for women than for men, while

  9. 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.

  10. Distribution of mast cells and macrophages and expression of interleukin-6 in periapical cysts.

    Science.gov (United States)

    Bracks, Igor Vieira; Armada, Luciana; Gonçalves, Lúcio Souza; Pires, Fábio Ramôa

    2014-01-01

    Mast cells and macrophages are important components of the inflammatory infiltrate found in inflammatory periapical diseases. Several cytokines participate in the mechanisms of inflammation, tissue repair, and bone resorption associated with periapical cysts. The aim of the present study was to evaluate the distribution of mast cells and macrophages and the expression of interleukin-6 (IL-6) in periapical cysts. Thirty periapical cysts were selected for the study, and clinical, demographic, and gross information from the cases was obtained from the laboratory records. Five-micrometer sections stained with hematoxylin-eosin were reviewed for analysis of the microscopic features of the cysts, and 3-μm sections on silanized slides were used for immunohistochemical reactions with anti-tryptase, anti-CD68, and anti-IL-6. There was no statistically significant difference in the mean number of mast cells and macrophages when comparing superficial and deep regions of the fibrous capsule of the cysts. Mean number of mast cells on the superficial region of the fibrous capsule was higher in cysts showing intense superficial inflammation and exocytosis. Macrophages were more commonly found in areas showing IL-6 expression, and IL-6 was less expressed in deep regions of the fibrous capsule in cysts showing greater gross volume. The results reinforced the participation of mast cells and macrophages in the pathogenesis of periapical cysts and suggested that IL-6 is not the major bone resorption mediator in larger periapical cysts. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  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

    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 m...... 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....... 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

  12. Levels of interleukin-6 in tears before and after excimer laser treatment

    Directory of Open Access Journals (Sweden)

    Resan Mirko

    2015-01-01

    Full Text Available Background/Aim. Immune response and consequent inflammatory process which originate on ocular surface after a trauma are mediated by cytokines. Photoablation of corneal stroma performed by excimer laser causes surgically induced trauma. Interleukin-6 (IL-6 is mostly known as a proinflammatory cytokine. However, it also has regenerative and anti-inflammatory effects. It is supposed that this cytokine is likely to play a significant role in the process of corneal wound healing response after photoablation of stroma carried out by laser in situ keratomileusis (LASIK or photorefractive keratectomy (PRK methods. The aim of this study was to determine and compare the levels of IL-6 in tears before and after treatment with LASIK and PRK methods. Methods. The study included 68 shortsighted eyes up to -3.0 diopter sphere, i.e. 198 samples of tears (per three samples taken from each of the eyes, divided into two groups according to the kind of excimer laser intervention performed: the group 1 - eyes treated by LASIK method (n = 31, and the group 2 - eyes treated by the PRK method (n = 37. The samples of tears were taken from each eye at the following time points: before excimer laser treatment (0 h, the control group, 1 h after the treatment (1 h and 24 h after the treatment (24 h. The patients did not use anti-inflammatory therapy 24 h after the intervention. Tear samples were collected using microsurgical sponge. Level of IL-6 in tear fluid was determined by the flow cytometry method, applying a commercial test kit which allowed cytokine detection from a small sample volume. Results. The values of IL-6 were detectable in 16% of samples before LASIK treatment and in 30% of samples before PRK treatment. One h after the treatment IL-6 was detectable in 29% of samples for the LASIK group and 43% of samples for the PRK group, and 24 h after the treatment it was detectable in 19% of samples for the LASIK group and in 57% of samples for the PRK group. When we

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

    Science.gov (United States)

    Attaran, Davood; Lari, Shahrzad M; Towhidi, Mohammad; Marallu, Hassan Ghobadi; Ayatollahi, Hossein; Khajehdaluee, Mohammad; Ghanei, Mostafa; Basiri, Reza

    2010-01-01

    Objectives Chronic obstructive pulmonary disease (COPD) is one of the main late complications of sulfur mustard poisoning. The aim of this study was to evaluate serum levels of interleukin (IL)-6 in war veterans with pulmonary complications of sulfur mustard poisoning and their correlation with severity of airways disease. Methods Fifty consecutive patients with sulfur mustard poisoning and stable COPD, and of mean age 46.3 ± 9.18 years were enrolled in this study. Thirty healthy men were selected as controls and matched to cases by age and body mass index. Spirometry, arterial blood gas, six- minute walk test, BODE (body mass index, obstruction, dyspnea, and exercise capacity), and St George’s Respiratory Questionnaire about quality of life were evaluated. Serum IL-6 was measured in both patient and control groups. Results Fifty-four percent of patients had moderate COPD. Mean serum IL-6 levels were 15.01 ± standard deviation (SD) 0.61 pg/dL and 4.59 ± 3.40 pg/dL in the case and control groups, respectively (P = 0.03). There was a significant correlation between IL-6 levels and Global Initiative for Chronic Obstructive Lung Disease stage (r = 0.25, P = 0.04) and between IL-6 and BODE index (r = 0.38, P = 0.01). There was also a significant negative correlation between serum IL-6 and forced expiratory volume in one second (FEV1, r = −0.36, P = 0.016). Conclusion Our findings suggest that serum IL-6 is increased in patients with sulfur mustard poisoning and COPD, and may have a direct association with airflow limitation. PMID:21037957

  14. IL-6, Antioxidant Capacity and Muscle Damage Markers Following High-Intensity Interval Training Protocols

    OpenAIRE

    Cipryan, Lukas

    2017-01-01

    Abstract The aim of this study was to investigate changes of interleukin-6 (IL-6), total antioxidant capacity (TAC) and muscle damage markers (creatine kinase (CK), myoglobin and lactate dehydrogenase (LDH)) in response to three different high-intensity interval training (HIIT) protocols of identical external work. Twelve moderately-trained males participated in the three HIIT trials which consisted of a warm-up, followed by 12 min of 15 s, 30 s or 60 s HIIT sequences with the work/rest ratio...

  15. 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.

  16. 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.

  17. MicroRNA-365 in macrophages regulates Mycobacterium tuberculosis-induced active pulmonary tuberculosis via interleukin-6.

    Science.gov (United States)

    Song, Qingzhang; Li, Hui; Shao, Hua; Li, Chunling; Lu, Xiao

    2015-01-01

    The present study is to investigate the relationship between microRNA (miR)-365 expression and the levels of interleukin (IL)-6 mRNA and protein in patients with active tuberculosis. From June 2011 to June 2014, 48 patients with active pulmonary tuberculosis induced by Mycobacterium tuberculosis were included in the study. In addition, 23 healthy subjects were enrolled as control. Macrophages were collected by pulmonary alveolus lavage. In addition, serum and mononuclear cells were isolated from peripheral blood. The levels of miR-365 and IL-6 in macrophages, mononuclear cells and serum were determined using quantitative real-time polymerase chain reaction. The protein expression of IL-6 in macrophages and mononuclear cells was measured using Western blotting, while that in serum was detected by enzyme-linked immunoabsorbent assay. Expression of IL-6 mRNA and protein was significantly enhanced in patients with active pulmonary tuberculosis. Increase of IL-6 protein concentration in serum was probably due to the release of IL-6 protein from mononuclear cells in the blood. In addition, miR-365 levels were significantly lowered in patients with active pulmonary tuberculosis. Up-regulated IL-6 expression in macrophages, mononuclear cells and serum in patients with active pulmonary tuberculosis is related to the down-regulation of miR-365, suggesting that miR-365 may regulate the occurrence and immune responses of active pulmonary tuberculosis via IL-6.

  18. Interleukin-6 and tumor necrosis factor-alpha values in elk neonates

    Science.gov (United States)

    Barber-Meyer, S. M.; Johnson, C.R.; Murtaugh, M.P.; Mech, L.D.; White, P.J.

    2007-01-01

    Serological indicators of general condition would be helpful for monitoring or assessing ungulate wildlife. Toward that end, we report the 1st reference values for 2 cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-??), in neonatal elk (Cervus elaphus). We obtained blood samples from 140 calves ??? 6 days old in Yellowstone National Park during summer 2003-2005. TL-6 values ranged from 0 to 1.21 pg/ml with a median of 0.03 pg/ml. TNF-?? values ranged from 0 to 225.43 pg/ml with a median of 1.85 pg/ml. IL-6 and TNF-?? concentrations were not significant predictors of elk calf survival through 21 days. Development of ungulate-based IL-6 and TNF-?? assays that provide greater sensitivity than cross-reacting human-based assays could be helpful in monitoring ungulate condition and health status comparisons among herds. Such information could provide indirect assessments of range quality or environmental influences among herds. 

  19. Levels of interleukin-6 in tears before and after excimer laser treatment.

    Science.gov (United States)

    Resan, Mirko; Stanojević, Ivan; Petković, Aleksandra; Pajić, Bojan; Vojvodić, Danilo

    2015-04-01

    Immune response and consequent inflammatory process which originate on ocular surface after a trauma are mediated by cytokines. Photoablation of corneal stroma performed by excimer laser causes surgically induced trauma. Interleukin-6 (IL-6) is mostly known as a proinflammatory cytokine. However, it also has regenerative and anti-inflammatory effects. It is supposed that this cytokine is likely to play a significant role in the process of corneal wound healing response after photoablation of stroma carried out by laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) methods. The aim of this study was to determine and compare the levels of IL-6 in tears before and after treatment with LASIK and PRK methods. The study included 68 shortsighted eyes up to -3.0 diopter sphere, i.e. 198 samples of tears (per three samples taken from each of the eyes), divided into two groups according to the kind of excimer laser intervention performed: the group 1--eyes treated by LASIK method (n=31), and the group 2--eyes treated by the PRK method (n=37). The samples of tears were taken from each eye at the following time points: before excimer laser treatment (0 h, the control group), 1 h after the treatment (1 h) and 24 h after the treatment (24 h). The patients did not use anti-inflammatory therapy 24 h after the intervention. Tear samples were collected using microsurgical sponge. Level of IL-6 in tear fluid was determined by the flow cytometry method, applying a commercial test kit which allowed cytokine detection from a small sample volume. Results. The values of IL-6 were detectable in 16% of samples before LASIK treatment and in 30% of samples before PRK treatment. One h after the treatment IL-6 was detectable in 29% of samples for the LASIK group and 43% of samples for the PRK group, and 24 h after the treatment it was detectable in 19% of samples for the LASIK group and in 57% of samples for the PRK group. When we analyzed the dynamics of IL76 production

  20. Genetic variant modifies the effect of N3 PUFAs on DNA methylation of IL6 in the Genetics of Lipid Lowering Drugs and Diet Network study

    Science.gov (United States)

    N3 polyunsaturated fatty acids (N3 PUFAs) ameliorate inflammation status with specific regulation on interleukin-6 (IL6) expression. However, the molecular mechanism for this regulation is unclear. Using both cell lines data from Encyclopedia of DNA Elements (ENCODE) consortium and population data f...

  1. 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.

  2. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase.

    Science.gov (United States)

    Brown, Charles O; Salem, Kelley; Wagner, Brett A; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R; Goel, Apollina

    2012-06-15

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plus IR demonstrated reduced annexin/propidium iodide staining, caspase 3 activation, PARP [poly(ADP-ribose) polymerase] cleavage and mitochondrial membrane depolarization with increased clonogenic survival. IL-6 combined with IR or Dex increased early intracellular pro-oxidant levels that were causally related to activation of NF-κB (nuclear factor κB) as determined by the ability of N-acetylcysteine to suppress both pro-oxidant levels and NF-κB activation. In myeloma cells, upon combination with hydrogen peroxide treatment, relative to TNF (tumour necrosis factor)-α, IL-6 induced an early perturbation in reduced glutathione level and increased NF-κB-dependent MnSOD (manganese superoxide dismutase) expression. Furthermore, knockdown of MnSOD suppressed the IL-6-induced myeloma cell resistance to radiation. MitoSOX Red staining showed that IL-6 treatment attenuated late mitochondrial oxidant production in irradiated myeloma cells. The present study provides evidence that increases in MnSOD expression mediate IL-6-induced resistance to Dex and radiation in myeloma cells. The results of the present study indicate that inhibition of antioxidant pathways could enhance myeloma cell responses to radiotherapy and/or chemotherapy.

  3. Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease.

    Science.gov (United States)

    Håkansson, Anna; Westberg, Lars; Nilsson, Staffan; Buervenich, Silvia; Carmine, Andrea; Holmberg, Björn; Sydow, Olof; Olson, Lars; Johnels, Bo; Eriksson, Elias; Nissbrandt, Hans

    2005-02-05

    The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (IL-6 and ERbeta SNPs were combined, the combination was much more robustly associated with PD, and especially with PD with an early age of onset, than respective GG genotype when analyzed separately. Our results indicate that the G-174C SNP in the IL-6 promoter may influence the risk for developing PD, particularly regarding early age of onset PD, and that the effect is modified by interaction of the G-1730A SNP in the ERbeta gene. (c) 2004 Wiley-Liss, Inc.

  4. Exercise promotes IL-6 release from legs in older men with minor response to unilateral immobilization

    DEFF Research Database (Denmark)

    Reihmane, Dace; Gram, Martin; Vigelsø Hansen, Andreas

    2016-01-01

    Physical inactivity is a major contributor to low-grade systemic inflammation. Most of the studies characterizing interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) release from exercising legs have been done in young, healthy men, but studies on inactivity in older people are lacking....... The impact of 14 days of one-leg immobilization (IM) on IL-6 and TNF-α release during exercise in comparison to the contralateral control (CON) leg was investigated. Fifteen healthy men (age 68.1 ± 1.1 year (mean ± SEM); BMI 27.0 ± 0.4 kg·m(2); VO2max 33.3 ± 1.6 ml·kg(‒1)·min(‒1)) performed 45 min of two......). There was no release of TNF-α in either leg and arterial concentrations remained unchanged during exercise (p > .05). In conclusion, exercise induces more pronounced IL-6 secretion in healthy older men. Two weeks of unilateral immobilization on the other hand had only a minor influence on IL-6 release. Neither...

  5. 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.

  6. Association of gene variants in TLR4 and IL-6 genes with Perthes disease

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    Srzentić Sanja

    2014-01-01

    Full Text Available Introduction. Perthes disease is idiopathic avascular osteonecrosis of the hip in children, with unknown etiology. Inflammation is present during development of Perthes disease and it is known that this process influences bone remodeling. Objective. Since genetic studies related to inflammation have not been performed in Perthes disease so far, the aim of this study was to analyze the association of frequencies of genetic variants of immune response genes, toll-like receptor 4 (TLR4 and interleukin-6 (IL-6, with this disease. Methods. The study cohort consisted of 37 patients with Perthes disease and 50 healthy controls. Polymorphisms of well described inflammatory mediators: TLR4 (Asp299Gly, Thr399Ile and IL-6 (G-174C, G- 597A were determined by polymerase chain reaction restriction fragment length polymorphism method. Results. IL-6 G-174C and G-597A polymorphisms were in complete linkage disequilibrium. A statistically significant increase of heterozygote subjects for IL-6 G-174C/G-597A was found in controls in comparison to Perthes patient group (p=0.047, OR=2.49, 95% CI=1.00-6.21. Also, the patient group for IL-6 G-174C/G- 597A polymorphisms was not in Hardy-Weinberg equilibrium. No statistically significant differences were found between patient and control groups for TLR4 analyzed polymorphisms. A stratified analysis by the age at disease onset also did not reveal any significant difference for all analyzed polymorphisms. Conclusion. Our study revealed that heterozygote subjects for the IL-6 G-174C/G-597A polymorphisms were significantly overrepresented in the control group than in the Perthes patient group. Consequently, we concluded that children who are heterozygous for these polymorphisms have a lower chance of developing Perthes disease than carriers of both homozygote genotypes. [Projekat Ministarstva nauke Republike Srbije, br. III41004

  7. Association of plasma IL-6 and Hsp70 with HRV at different levels of PAHs metabolites.

    Directory of Open Access Journals (Sweden)

    Jian Ye

    Full Text Available Exposure to polycyclic aromatic hydrocarbons (PAHs is associated with reduced heart rate variability (HRV, a strong predictor of cardiovascular diseases, but the mechanism is not well understood.We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6 and heat shock protein 70 (Hsp70 were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs were measured by gas chromatography-mass spectrometry.We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05; and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP and low frequency (LF (Ptrend = 0.014 and 0.006, respectively. In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all Ptrend<0.05, but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN, TP and LF in the low-PAHs metabolites groups (all Ptrend<0.05. We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.

  8. Sex difference in link between interleukin-6 and stress.

    Science.gov (United States)

    Jankord, Ryan; Turk, James R; Schadt, James C; Casati, Jennifer; Ganjam, Venkataseshu K; Price, Elmer M; Keisler, Duane H; Laughlin, M Harold

    2007-08-01

    Inflammation contributes to disease development, and the neuroimmunoendocrine interface is a potential site of action for inflammatory products like IL-6 to affect health. Although plasma IL-6 can stimulate the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis, the precise role, if any, for IL-6 in the HPA response to nonimmunological stressors is unclear. The purpose of this study was to test the hypothesis that IL-6 in the stalk median eminence (SME) can be directly involved in stimulating ACTH secretion in response to acute stress in female swine. This study was undertaken as a result of finding IL-6 localized to the external zone of the SME next to the hypophyseal portal vessels. Results indicate that content of IL-6 in the SME decreases in response to acute stress along with an increase in nuclear phosphorylated signal transducer and activator of transcription-3 (pSTAT-3) in pituitary corticotrophs and a simultaneous increase in plasma concentrations of IL-6 and ACTH. Furthermore, we show that females concomitantly display greater SME content of IL-6 and greater HPA responsiveness to stress, thereby suggesting that IL-6 release from the SME is an integral factor contributing to enhanced stress responsiveness in females. Our results provide evidence for a direct link between IL-6 and ACTH release and reveal a sex difference in this relationship.

  9. Levosimendan reduces plasma B-type natriuretic peptide and interleukin 6, and improves central hemodynamics in severe heart failure patients.

    Science.gov (United States)

    Kyrzopoulos, Stamos; Adamopoulos, Stamatis; Parissis, John T; Rassias, John; Kostakis, George; Iliodromitis, Efstathios; Degiannis, Dimitrios; Kremastinos, Dimitrios Th

    2005-03-30

    Plasma B-type natriuretic peptide (BNP) and interleukin 6 (IL-6) levels have recently been demonstrated as significant neurohormonal markers associated with the progression of chronic heart failure (CHF). Additionally, clinical studies have shown that the calcium sensitizer, levosimendan, beneficially affects the central hemodynamics of CHF patients and improves their long-term prognosis. This study investigates whether levosimendan-induced hemodynamic improvement of CHF patients is related to the respective changes of NT-proBNP and IL-6 levels. Circulating levels of NT-pro BNP and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) in 12 patients with decompensated advanced CHF at baseline, immediately after the end of a 24-h levosimendan infusion and 72 h after the initiation of treatment. Hemodynamic parameters of patients (pulmonary wedge and pulmonary artery pressure (PAP), systemic and pulmonary vascular resistance (PVR), stroke volume, and cardiac output and index) were also monitored during the same period. NT-proBNP and IL-6 levels were significantly reduced in severe CHF patients within 72 h after the initiation of levosimendan treatment (pNT-proBNP levels and the respective reduction of pulmonary wedge pressure (r(s)=0.65, pBNP and IL-6 levels may be useful biochemical markers related with the levosimendan-induced improvement in central hemodynamics and the clinical status of decompensated advanced CHF patients.

  10. 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.

  11. CHANGES IN RESTING SALIVARY TESTOSTERONE, CORTISOL AND INTERLEUKIN-6 AS BIOMARKERS OF OVERTRAINING.

    Science.gov (United States)

    Anderson, Travis; Haake, Simon; Lane, Amy R; Hackney, Anthony C

    2016-01-01

    Overtraining (OVT) is a concern for many athletes. Immunological (increased interleukin-6 [IL-6]) and hormonal (increased cortisol [C], decreased free testosterone [fT]) biomarkers have been analyzed during training to detect OVT development. This study determined if resting levels of salivary IL-6, T, and C change during a pre-season resistance training (RT) program in 20 Division I American football players (mean ± SD: age = 19.1 ± 1.1 years; height = 185.4 ± 6.7 cm; mass = 102.0 ± 22.2 kg; body fat = 14.7 ± 7.6%). 1RM squat, bench press and Olympic-style clean, IL-6, C and T were assessed at baseline (WK1), week 4 (WK4), week 6 (WK6) along with psychological status (PS) to determine affective state. 1RM (bench press: 121.6 ± 36.3 kg vs. 127.4 ± 35.9 kg, squat: 187.2 ± 30.2 kg, 190.9 ± 28.1 kg, clean: 116.8 ± 14.6 kg, vs. 119.2 ± 14.5 kg), IL-6 (1.42 ± 1.77 pg/mL vs. 5.60 ± 12.57 pg/mL) and C (2.57 ± 2.46 nmol/L vs. 5.33 ± 4.94) increased signihcantly from WK1 to WK6 ( p < .05), fT decreased signihcantly (417.44 ± 83.63 pmol/Lvs. 341.10 ± 87.79 pmol/L) from WK1 to WK6 ( p < .05). PS was minimally affected during the study. Signihcant biomarker changes were detected, but no OVT was induced (i.e. performance improved). Therefore, directional changes in these biomarkers may not be sufficiently reflective of OVT in RT programs.

  12. 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

  13. Optimized PCR with sequence specific primers (PCR-SSP for fast and efficient determination of Interleukin-6 Promoter -597/-572/-174Haplotypes

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    Bugert Peter

    2009-12-01

    Full Text Available Abstract Background Interleukin-6 (IL-6 promoter polymorphisms at positions -597(G→A, -572(G→C and -174(G→C were shown to have a clinical impact on different major diseases. At present PCR-SSP protocols for IL-6 -597/-572/-174haplotyping are elaborate and require large amounts of genomic DNA. Findings We describe an improved typing technique requiring a decreased number of PCR-reactions and a reduced PCR-runtime due to optimized PCR-conditions. Conclusion This enables a fast and efficient determination of IL-6 -597/-572/-174haplotypes in clinical diagnosis and further evaluation of IL-6 promoter polymorphisms in larger patient cohorts.

  14. 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.

  15. Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass

    DEFF Research Database (Denmark)

    Kirchner, Henriette; Nylen, Carolina; Laber, Samantha

    2014-01-01

    methylation of selected promoter regions was measured in whole blood before and after VLCD. A subgroup of seven patients was studied 1–2 days and 12± 3 months after RYGB. Promoter methylation was measured using methylated DNA capture and quantitative real-time polymerase chain reaction (PCR). Results VLCD....... The objective of this study was to test whether promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1 A), pyruvate dehydrogenase kinase isozyme-4 (PDK4), transcription factor A (TFAM), interleukin-1 beta (IL1 B), interleukin-6 (IL6) and tumor necrosis factor...... decreased promoter methylation of PPARGC1 A. Methylation of PPARGC1 A, TFAM, IL1 B, IL6, and TNF promoters was changed two days after RYGB. Similar changes were also seen on day one after cholecystectomy. Moreover, methylation increased in PDK4, IL1 B, IL6, and TNF promoters 12 months after RYGB. Conclusion...

  16. 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, P<.001). Higher associations between polymorphism at IL-6 -174G/C and bronchial asthma were observed in atopic patients (OR=4.1, 95% CI: 2.308-7.280, P<8.10 -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.

  17. Downregulation of IL6 Targeted MiR-376b May Contribute to a Positive IL6 Feedback Loop During Early Liver Regeneration in Mice

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    Shan Lu

    2015-08-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs are a group of endogenous, small, noncoding RNAs implicated in a variety of biological processes, including cell proliferation, apoptosis, differentiation and metabolism. The present study aims to explore the potential role and molecular mechanism of miR-376b during the early phase of liver regeneration. Methods: MiRNA profiling microarrays were used to assess the changes in miRNA expression. For functional analysis, cell proliferation, apoptosis assays, real time quantitative PCR and westernblot analysis were performed. Results: The comprehensive miRNA expression profiling assays on regenerating liver tissues 4 h after partial hepatectomy (PH showed that three miRNAs (miR-127, miR-376b and miR-494 located in the Dlk1-Gtl2 miRNA cluster were significantly downregulated. In vitro functional studies demonstrated that high-level interleukin 6 (IL6 inhibited the expression of miR-376b, and miR-376b mimics treatment decreased cell proliferation and increased apoptosis. Further target analysis showed that miR-376b reduced the mRNA and protein expression levels of NF-kappa-B inhibitor zeta (NFKBIZ and signal transducers and transcription activators 3 (STAT3. Additionally, IL6-induced miR-376b downregulation would, in turn, increase the expression of IL-6 possibly via a feedback loop involving NFKBIZ or/and STAT3. Conclusion: During the early phase of liver regeneration, miR-376b expression was significantly decreased. Our findings reveal that a regulatory circuitry between miR-376b and IL-6 may exist, which trigger the initiation of liver regeneration.

  18. Influence of IL-6 and bone metabolic markers on bone absorption and osteogenesis

    International Nuclear Information System (INIS)

    Yin Qiuxia; Luo Nanping; Wang Ruishan; Chen Yingjian; Niu Aijun; Sun Xiaoming

    2003-01-01

    Objective: To study the role of IL-6 and bone metabolic markers in the pathogenesis of osteoporosis in aged men. Methods: Serum IL-6, bone glaprotein (BGP), testosterone (T), ALP and Ca were measured in 90 old male subjects with RIA and biochemical analytical method. The tested subjects consisted of 40 cases of osteoporosis and 50 cases of decreased bone mass. The values were compared with those in 32 healthy old males and 35 younger subjects as controls. Results: Bone absorption marker (IL-6) increased with severity of osteoporosis and the levels were significantly higher than those in controls (p < 0.01). Osteogenesis marker (BGP, SALP and T) decreased by different degrees and were significant lower than those in controls (p < 0.05, p < 0.01). Conclusion: Abnormal serum level of IL-6 and other bone metabolic markers might indicate increased bone absorption and decreased osteogenesis, which were the characteristics of osteoporosis in aged men

  19. The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome.

    Science.gov (United States)

    Ciftci, Tansu Ulukavak; Kokturk, Oguz; Bukan, Neslihan; Bilgihan, Ayse

    2004-10-21

    Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may have a direct effect on glucose and lipid metabolism. On the other hand, it is known that IL-6 and TNF-alpha are important pro-inflammatory cytokines in the pathogenesis of atherosclerosis. The goal of present study was to test whether sleep apnea contributes to the previously reported increases of IL-6 and TNF-alpha independent of obesity. Forty-three obese (body mass index, BMI>27 kg/m2) men with newly diagnosed obstructive sleep apnea syndrome (OSAS) (apnea-hypopnea index, AHI> or =5) and age- and BMI-matched 22 obese nonapneic male controls (AHI<5) were enrolled in this study. To confirm the diagnosis, all patients underwent standard polysomnography in the sleep disorders center. Serum samples were taken at 08:00 h in the morning after overnight fasting. Serum IL-6 and TNF-alpha levels were found significantly higher in OSAS patients than in controls (p=0.002, p=0.03). Serum IL-6 and TNF-alpha levels were significantly correlated with AHI in OSAS patients (r=0.03, p=0.046 and r=0.36, p=0.016). There was no significant correlation between serum IL-6, TNF-alpha levels and AHI in controls. Serum IL-6 and TNF-alpha levels were not correlated with BMI both in OSAS patients and controls. In conclusion, circulating IL-6 and TNF-alpha levels in patients with OSAS, as independent of BMI are significantly higher than levels in controls and there is a positive relationship between previously mentioned cytokines' levels and the severity of OSAS. According to these results, the link between cardiovascular morbidity and OSAS may be explained by the coexistence of other cardiovascular risk factors such as circulating IL-6 and TNF-alpha levels.

  20. The G to C polymorphism at -174 of the interleukin-6 gene is rare in a Southern Chinese population

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, R.H.; Liu, G.; Yang, C.M.; Huang, C.H.; Wu, C.R.; Christiani, D.C. [Harvard University, Boston, MA (United States). School of Public Health, Occupational Health Programme, Dept. of Environmental Health

    2001-11-01

    Interleukin-6 is thought to be involved in the pathogenesis of coal workers' pneumoconiosis. Recently, a functional G to C polymorphism at position -174 of the promoter of the IL-6 gene has been described. The -174 polymorphisms in 259 retired Chinese men from Guangxi province (all retired coal miners) were examined. Only one GC heterozygous and no CC homozygous variants were found. Our results suggest that the frequency of the C allele in this Chinese population is lower than in Caucasian and east Indian populations.

  1. Discordant gene expression in skeletal muscle and adipose tissue of patients with type 2 diabetes: effect of interleukin-6 infusion

    DEFF Research Database (Denmark)

    Carey, A.; Wolsk, Emil; Bruce, C.

    2006-01-01

    Aims/hypothesis  We compared metabolic gene expression in adipose tissue and skeletal muscle from patients with type 2 diabetes and from well-matched healthy control subjects. We hypothesised that gene expression would be discordantly regulated when comparing the two groups. Our secondary aim...... was to determine the effect of Interleukin-6 (IL6) infusion on circulating adipokines and on gene expression in human adipose tissue. To do this we used real-time RT-PCR. Methods  Both diabetic and control subjects underwent basal skeletal muscle and subcutaneous adipose tissue biopsies. A subset...... necrosis factor alpha, adiponectin and resistin were all unaffected by IL6 infusion, but plasma resistin was lower in the diabetic subjects than in control subjects. Conclusions/interpretation  The observation that PPARGC1A and the PPARs were upregulated in the adipose tissue of type 2 diabetic patients...

  2. Potential use of recombinant human interleukin-6 in clinical oncology

    NARCIS (Netherlands)

    Veldhuis, GJ; Willemse, PHB; Mulder, NH; Limburg, PC; deVries, EGE

    Recombinant human IL-6 (rhIL-6) is a pleiotropic cytokine with stimulatory actions on the hematopoietic system, the immune system and hepatocytes. Clinical interest in the use of this cytokine was raised because of its thrombopoietic properties and also because of its anti-tumor activity, which was

  3. Simultaneous immunoassay analysis of plasma IL-6 and TNF-α on a microchip.

    Directory of Open Access Journals (Sweden)

    Kaori Abe

    Full Text Available Sandwich enzyme-linked immunosorbant assay (ELISA using a 96-well plate is frequently employed for clinical diagnosis, but is time-and sample-consuming. To overcome these drawbacks, we performed a sandwich ELISA on a microchip. The microchip was made of cyclic olefin copolymer with 4 straight microchannels. For the construction of the sandwich ELISA for interleukin-6 (IL-6 or tumor necrosis factor-α (TNF-α, we used a piezoelectric inkjet printing system for the deposition and fixation of the 1st anti-IL-6 antibody or 1st anti-TNF-α antibody on the surface of the each microchannel. After the infusion of 2 µl of sample to the microchannel and a 20 min incubation, 2 µl of biotinylated 2nd antibody for either antigen was infused and a 10 min incubation. Then 2 µl of avidin-horseradish peroxidase was infused; and after a 5 min incubation, the substrate for peroxidase was infused, and the luminescence intensity was measured. Calibration curves were obtained between the concentration and luminescence intensity over the range of 0 to 32 pg/ml (IL-6: R(2 = 0.9994, TNF-α: R(2 = 0.9977, and the detection limit for each protein was 0.28 pg/ml and 0.46 pg/ml, respectively. Blood IL-6 and TNF-α concentrations of 5 subjects estimated from the microchip data were compared with results obtained by the conventional method, good correlations were observed between the methods according to linear regression analysis (IL-6: R(2 = 0.9954, TNF-α: R(2 = 0.9928. The reproducibility of the presented assay for the determination of the blood IL-6 and TNF-α concentration was comparable to that obtained with the 96-well plate. Simultaneous detection of blood IL-6 and TNF-α was possible by the deposition and fixation of each 1st antibody on the surface of a separate microchannel. This assay enabled us to determine simultaneously blood IL-6 and TNF-α with accuracy, satisfactory sensitivity, time saving ability, and low consumption of sample and

  4. Interleukin-6 downregulated vascular smooth muscle cell contractile proteins via ATG4B-mediated autophagy in thoracic aortic dissection.

    Science.gov (United States)

    An, Zhao; Qiao, Fan; Lu, Qijue; Ma, Ye; Liu, Yang; Lu, Fanglin; Xu, Zhiyun

    2017-12-01

    Interleukin-6 (IL-6) overexpression played an important role in the pathogenesis of thoracic aortic dissection (TAD). Our previous study found enhanced autophagy accompanying with contractile proteins α smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α) degradation in TAD aortic vascular smooth muscle cells (VSMCs). Autophagy is an important way for intracellular proteins degradation, while IL-6 has been found as a contributing factor of autophagy in some cancers. These indicated IL-6 might contribute to the occurrence of TAD by promoting autophagy-induced contractile proteins degradation, which has not been investigated. The aim of the present study is to verify this hypothesis and investigate the mechanism of it. We collected 10 TAD and 10 control aortic specimens from patients underwent TAD surgical repair and coronary artery bypass grafting, respectively. Quantitative real-time polymerase chain reaction was used to detect mRNA expression. Protein expression level was assessed by enzyme-linked immunosorbent assay, western blot, and immunohistochemistry. Microtubule-associated protein 1 light chain 3 beta overexpression adenovirus with green and red fluorescent protein tags and transmission electron microscopy were used to detect autophagy level in VSMCs. 3-Methyladenine (3-MA) and chloroquine were used to block autophagy in human VSMCs. Experiment results showed that the expression of IL-6 was significantly increased accompanying with up-regulated autophagy in TAD aortic wall compared with controls. In vitro results showed that IL-6 stimulation decreased the expression of VSMCs contractile proteins α-SMA and SM22α accompanying with up-regulated autophagy. Blocking autophagy with 3-MA or chloroquine inhibited IL-6 induced α-SMA and SM22α degradation. Further investigation showed that autophagy-related 4B cysteine peptidase (ATG4B) was significantly overexpressed in TAD aortic wall and played important role in IL-6 induced autophagy up

  5. Complete physical mapping of IL6 reveals a new marker associated with chronic periodontitis.

    Science.gov (United States)

    Farhat, S B; de Souza, C M; Braosi, A P R; Kim, S H; Tramontina, V A; Papalexiou, V; Olandoski, M; Mira, M T; Luczyszyn, S M; Trevilatto, P C

    2017-04-01

    Interleukin-6 (IL-6) is a powerful stimulator of osteoclast differentiation and bone resorption. Production of IL-6 is modulated by polymorphisms, and higher levels of this cytokine are found locally in patients with chronic periodontitis. In this study we performed a modern approach - Complete physical mapping of the IL6 gene - to identify the polymorphisms associated with chronic periodontitis in a southern Brazilian population sample. One-hundred and nine individuals of both genders (mean age: 41.5 ± 8.5 years) were divided into a study group (56 participants with periodontitis) and a control group (53 individuals without periodontitis). After collection and purification of DNA, nine tag single nucleotide polymorphisms (SNPs; rs1524107, rs2069835, rs2069837, rs2069838, rs2069840, rs2069842, rs2069843, rs2069845 and rs2069849) covering the entire gene were selected according to the information available on the International HapMap Project website and evaluated using real-time PCR. Differences in the distribution of the following parameters were statistically significant between study and control groups: number of teeth (p = 0.030); probing depth (p chronic periodontitis in a Brazilian population in the presence of clinical variables, such as visible plaque, dentist visit frequency and dental floss use, and was suggested for the first time as a marker of susceptibility to chronic periodontitis. Complete physical mapping of IL6 (using tag SNPs) was carried out for the first time, unveiling allele G of polymorphism rs2069837 (located in the second intron of IL6) as a suggestive marker of protection against chronic periodontitis in a Brazilian population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. The influence of age and repeated LPS administration on body temperature and the relation with interleukin-6 and IgM antibodies in broiler chickens

    OpenAIRE

    De Boever , Sandra; Beyaert , Rudi; Vandemaele , Fréderic; Baert , Kris; Duchateau , Luc; Goddeeris , Bruno; De Backer , Patrick; Croubels , Siska

    2008-01-01

    Abstract Our objective was to create a standardized and reproducible inflammation model in chickens in order to study the pharmacodynamics of several anti-pyretic and anti-inflammatory drugs. We studied the influence of age and repeated lipopolysaccharide (LPS) administration on body temperature and the correlation of this with concentrations of interleukin 6 (IL-6) and IgM antibodies against LPS in plasma of chickens. Three and five week old broilers were injected intravenously...

  7. Ultraviolet radiation-induced interleukin 6 release in HeLa cells is mediated via membrane events in a DNA damage-independent way.

    Science.gov (United States)

    Kulms, D; Pöppelmann, B; Schwarz, T

    2000-05-19

    Evidence exists that ultraviolet radiation (UV) affects molecular targets in the nucleus or at the cell membrane. UV-induced apoptosis was found to be mediated via DNA damage and activation of death receptors, suggesting that nuclear and membrane effects are not mutually exclusive. To determine whether participation of nuclear and membrane components is also essential for other UV responses, we studied the induction of interleukin-6 (IL-6) by UV. Exposing HeLa cells to UV at 4 degrees C, which inhibits activation of surface receptors, almost completely prevented IL-6 release. Enhanced repair of UV-mediated DNA damage by addition of the DNA repair enzyme photolyase did not affect UV-induced IL-6 production, suggesting that in this case membrane events predominant over nuclear effects. UV-induced IL-6 release is mediated via NFkappaB since the NFkappaB inhibitor MG132 or transfection of cells with a super-repressor form of the NFkappaB inhibitor IkappaB reduced IL-6 release. Transfection with a dominant negative mutant of the signaling protein TRAF-2 reduced IL-6 release upon exposure to UV, indicating that UV-induced IL-6 release is mediated by activation of the tumor necrosis factor receptor-1. These data demonstrate that UV can exert biological effects mainly by affecting cell surface receptors and that this is independent of its ability to induce nuclear DNA damage.

  8. Additive prognostic value of interleukin-6 at peak phase of dobutamine stress echocardiography in patients with coronary artery disease. A 6-year follow-up study.

    Science.gov (United States)

    Ikonomidis, Ignatios; Athanassopoulos, George; Stamatelopoulos, Kimon; Lekakis, John; Revela, Ioanna; Venetsanou, Kiriaki; Marinou, Margarita; Monaco, Claudia; Cokkinos, Dennis V; Nihoyannopoulos, Petros

    2008-08-01

    Interleukin-6 (IL-6) and tissue factor (TF) are elevated after myocardial ischemia during dobutamine stress echo (DSE). We examined the incremental prognostic value of IL-6 or TF measured during DSE over echocardiographic and clinical factors in patients with chronic coronary artery disease (CAD). We studied 106 patients with angiographically documented CAD. IL-6 and TF were measured at rest, peak, and during recovery. A wall motion score index was calculated. Fifty-seven (54%) patients had ischemia at DSE. During follow-up (63.7 +/- 20 months), 36 patients (33%) had an adverse event (12 cardiac deaths, 24 acute coronary events). Patients with events had a higher peak IL-6 (P = .02) but similar rest and recovery IL-6 than those without. Patients with peak IL-6 > or =3.14 pg/mL (upper tertile) had a hazard ratio of 2.7 (95% CI 1.44-5.37) (P statistic from 0.66 to 0.70 (P = .04). The addition of peak IL-6 further increased the model's c statistic to 0.75 (P = .04). Tissue factor was not related with cardiac events. Interleuikin-6 levels measured during the peak phase of DSE incrementally contribute to risk stratification in patients with chronic CAD.

  9. Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.

    Science.gov (United States)

    Bharti, Rashmi; Dey, Goutam; Das, Anjan Kumar; Mandal, Mahitosh

    2018-04-26

    Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis. We employed various in-vitro and in-vivo techniques and clinical samples. We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen. Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.

  10. Fish Oil Supplementation Reduces Heart Levels of Interleukin-6 in Rats with Chronic Inflammation due to Epilepsy

    Directory of Open Access Journals (Sweden)

    Mariana Bocca Nejm

    2017-06-01

    Full Text Available Sudden unexpected death in epilepsy (SUDEP is a major cause of premature death related to epilepsy. The causes of SUDEP remain unknown, but cardiac arrhythmias and asphyxia have been suggested as a major mechanism of this event. Inflammation has been implicated in the pathogenesis of both epilepsy and ventricular arrhythmia, with interleukin-6 (IL-6 being recognized as a crucial orchestrator of inflammatory states. Our group previously reported that levels of IL-6 were increased in the hearts of epileptic rats. In this scenario, anti-inflammatory actions are among the beneficial effects of fish oil dietary supplementation. This investigation revealed that elevated levels of IL-6 in the heart were markedly reduced in epileptic rats that were treated in the long-term with fish oil, suggesting protective anti-inflammatory actions against dangerously high levels of IL-6. Based on these findings, our results suggest beneficial effects of long-term intake of fish oil in reducing the inflammation associated with chronic epilepsy.

  11. Interleukin-6-driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism.

    Science.gov (United States)

    Frampton, Gabriel; Invernizzi, Pietro; Bernuzzi, Francesca; Pae, Hae Yong; Quinn, Matthew; Horvat, Darijana; Galindo, Cheryl; Huang, Li; McMillin, Matthew; Cooper, Brandon; Rimassa, Lorenza; DeMorrow, Sharon

    2012-02-01

    Cholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. The growth factor, progranulin, is overexpressed in a number of tumours. The study aims were to assess the expression of progranulin in cholangiocarcinoma and to determine its effects on tumour growth. The expression and secretion of progranulin were evaluated in multiple cholangiocarcinoma cell lines and in clinical samples from patients with cholangiocarcinoma. The role of interleukin 6 (IL-6)-mediated signalling in the expression of progranulin was assessed using a combination of specific inhibitors and shRNA knockdown techniques. The effect of progranulin on proliferation and Akt activation and subsequent effects of FOXO1 phosphorylation were assessed in vitro. Progranulin knockdown cell lines were established, and the effects on cholangiocarcinoma growth were determined. Progranulin expression and secretion were upregulated in cholangiocarcinoma cell lines and tissue, which were in part via IL-6-mediated activation of the ERK1/2/RSK1/C/EBPβ pathway. Blocking any of these signalling molecules, by either pharmacological inhibitors or shRNA, prevented the IL-6-dependent activation of progranulin expression. Treatment of cholangiocarcinoma cells with recombinant progranulin increased cell proliferation in vitro by a mechanism involving Akt phosphorylation leading to phosphorylation and nuclear extrusion of FOXO1. Knockdown of progranulin expression in cholangiocarcinoma cells decreased the expression of proliferating cellular nuclear antigen, a marker of proliferative capacity, and slowed tumour growth in vivo. Evidence is presented for a role for progranulin as a novel growth factor regulating cholangiocarcinoma growth. Specific targeting of progranulin may represent an alternative for the development of therapeutic strategies.

  12. 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.

  13. IL-6 Promotes FSH-Induced VEGF Expression Through JAK/STAT3 Signaling Pathway in Bovine Granulosa Cells

    Directory of Open Access Journals (Sweden)

    Meng Yang

    2017-11-01

    Full Text Available Background/Aims: Vascular endothelial growth factor (VEGF has been demonstrated to play a pivotal role in the regulation of angiogenesis in ovarian follicular development, particularly during the preovulatory period. Although numerous studies have shown that interleukin-6 (IL-6 is one of the major inducing factors that regulate the expression of VEGF in non-ovarian cells, whether it involved in regulating the expression of VEGF in normal ovarian granulosa cells is still unknown. The aim of this study was to elucidate the mechanisms underlying the effect of IL-6 on FSH-induced VEGF expression in bovine granulosa cells derived from large follicles. Methods: VEGF mRNA expression in granulosa cells after IL-6 with/without inhibitors treatment was analyzed by RT-qPCR. Phosphorylation levels of ERK1/2 and STAT3 proteins induced by IL-6 were analyzed by western blotting. The protein levels produced by granulosa cells were detected by ELISA. Results: High concentration of IL-6 (10ng/ml can significantly up-regulate FSH-induced VEGF gene and protein expression levels in granulosa cells, and also promote the VEGF upstream regulators HIF-1α and COX2 mRNA expression. VEGF expression levels were significantly decreased after specifically blocking HIF-1α and COX2 by using inhibitors. The up-regulation effect of IL-6 on FSH-induced VEGF expression in granulosa cells mainly through activating the JAK/STAT3 signaling pathway, which can be impaired by JAK inhibitors. Conclusion: IL-6 can promote FSH-induced VEGF expression in granulosa cells, which is mainly achieved by increasing the expression of HIF-1α and COX2.This promoting effect is mediated by activating the JAK/STAT3 pathway. Moreover, there may be a synergistic relationship between FSH and IL-6 in the regulation of VEGF expression.

  14. 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.

  15. Interferon β protects against avascular osteonecrosis through interleukin 6 inhibition and silent information regulator transcript-1 upregulation.

    Science.gov (United States)

    Kim, Kyoung Min; Wagle, Sajeev; Moon, Young Jae; Wang, Sung Il; Park, Byung-Hyun; Jang, Kyu Yun; Kim, Jung Ryul

    2018-01-09

    Synovitis of the affected joint is a common in avascular osteonecrosis (AVN). Increased levels of pro-inflammatory cytokine interleukin-6 (IL-6) have been reported in AVN, but the mechanism of this increase remains unclear. Silent information regulator transcript-1 (SIRT1), an NAD-dependent deacetylase, inhibits the release of inflammatory cytokines. Interferon β (IFN-β) has clear anti-inflammatory properties. We sought to investigate the effects of IFN-β treatment on AVN and to evaluate the specific signal pathway relating to IL-6 and SIRT1 affected during AVN. Using a dissection microscope, AVN was surgically induced in the distal femurs of mice. Exogenous IFN-β was administered to the model mice. The effects of exogenous IFN-β on AVN model mice were assessed using hematoxylin eosin and safranin-O staining, and bone resorption activity was measured using tartrate-resistant acid phosphatase (TRAP) and CD68 staining. Western blots, real-time RT-PCR, and immunohistochemical staining were performed to evaluate the production of SIRT1 and IL-6 in tissues. The RAW 264.7 cell line and bone marrow derived osteoclasts treated with exogenous IFN-β. Histological findings indicated well preserved trabecular bone and decreased osteoclast bone resorption activity in IFN-β treated mice compared with mice in the AVN group. Treatment with IFN-β increased SIRT1 expression and inhibited secretion of IL-6 in this AVN mouse model. IFN-β decreased IL-6 secretion by activating SIRT1 in the RAW 264.7 cell and bone marrow derived osteoclasts. Our work suggests that IFN-β could be used to treat AVN and that both SIRT1 and IL-6 are useful targets for treating patients with AVN.

  16. The correlation of adiponectin, IL-6 with insulin resistance and macrovascular lesion in type 2 diabetes

    International Nuclear Information System (INIS)

    Shi Bimin; Cheng Xingbo

    2006-01-01

    Objective: To investigate the serum level changes of adiponectin and IL-6 and their relation with macrovascular complications in patients with type 2 diabetes before and after thiazolidinediones intervention. Methods: Serum adiponectin and IL-6 level were examined using ELISA method in 16 patients with obese type 2 diabetes, 24 patients with diabetes with normal body weight, and 14 controls. Their body mass index (BMI) and HOMA-IR were calculated and the internal membrane thickness (IMT) of carotid artery was also observed. These indexes were reexamined after thiazolidinediones (Avandia) intervention and correlation analysis was performed. Results: A decreased serum concentration of adiponectin and an elevated level of IL-6 and HOMA-IR were found in diabetes group especially in those with obesity (P<0.01). Serum adiponectin was negatively correlated with HOMA-IR, BMI, IL-6 and IMT while IL-6 was positively correlated with the above-mentioned indexes. After treatment with thiazolidinediones, the insulin resistance state and adponectin and IL-6 were significantly improved especially in those with obesity (P<0.05, P<0.01). Conclusion: Adiponectin is closed correlated with obesity (P<0.05, P<0.01). Conclusion: Adiponectin is closed correlated with obesity, insulin resistance and macrovascular lesions. IL-6 may be involved in the mechanism of insulin resistance in type 2 diabetes patients especially in the obese diabetes group. In addition to enhance the sensitivity of insulin, thiazolidinediones may play a potential role in anti-inflammation, anti-atherosclerosis and immuno-regulation. (authors)

  17. Induction of interleukin-6 by coal containing bioavailable iron is ...

    Indian Academy of Sciences (India)

    Unknown

    Coal mining causes health problems, such as pneumoconiosis. We have ... levels. The enhancing effect on the IL-6 by the PA coal was similar to that caused by hydrogen peroxide. ..... stress: possible implications in coal workers' lung disease;.

  18. Imaging colon cancer development in mice: IL-6 deficiency prevents adenoma in azoxymethane-treated Smad3 knockouts

    Science.gov (United States)

    Harpel, Kaitlin; Leung, Sarah; Faith Rice, Photini; Jones, Mykella; Barton, Jennifer K.; Bommireddy, Ramireddy

    2016-02-01

    The development of colorectal cancer in the azoxymethane-induced mouse model can be observed by using a miniaturized optical coherence tomography (OCT) imaging system. This system is uniquely capable of tracking disease development over time, allowing for the monitoring of morphological changes in the distal colon due to tumor development and the presence of lymphoid aggregates. By using genetically engineered mouse models deficient in Interleukin 6 (IL-6) and Smad family member 3 (Smad3), the role of inflammation on tumor development and the immune system can be elucidated. Smad3 knockout mice develop inflammatory response, wasting, and colitis associated cancer while deficiency of proinflammatory cytokine IL-6 confers resistance to tumorigenesis. We present pilot data showing that the Smad3 knockout group had the highest tumor burden, highest spleen weight, and lowest thymus weight. The IL-6 deficiency in Smad3 knockout mice prevented tumor development, splenomegaly, and thymic atrophy. This finding suggests that agents that inhibit IL-6 (e.g. anti-IL-6 antibody, non-steroidal anti-inflammatory drugs [NSAIDs], etc.) could be used as novel therapeutic agents to prevent disease progression and increase the efficacy of anti-cancer agents. OCT can also be useful for initiating early therapy and assessing the benefit of combination therapy targeting inflammation.

  19. 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

  20. Correlation between interleukin-6 and primary hepatocellular carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    LI Xia

    2015-06-01

    Full Text Available ObjectiveTo evaluate the correlation between interleukin (IL6 and primary hepatocellular carcinoma (HCC. MethodsCase-control studies that included quantitative data on plasma or serum IL-6 levels of patients with HCC were identified from PubMed, ISI Web of Knowledge, CBM, and CNKI. A meta-analysis was performed to quantitatively and comprehensively analyze data. ResultsTwenty-five studies were included and the meta-analysis was conducted separately for 3 groups: HCC vs controls, HCC vs liver cirrhosis, and HCC vs hepatitis. The serum IL-6 levels of patients with HCC were significantly higher than those of healthy controls (25 studies, standardized mean difference (SMD 5.02, 95% CI: 4.13-5.91, Z=11.05, P<0.000 1, patients with liver cirrhosis (15 studies, SMD=236, 95% CI: 1.54-3.19, Z=5.60, P<0.000 1, and patients with hepatitis (7 studies, SMD=2.63, 95% CI: 1.24-4.03, Z=369, P=0.000 2. ConclusionThe inflammatory mediator, IL-6, may play an important role in the development and progression of HCC.

  1. Determinants of IL-6 levels during HIV infection

    DEFF Research Database (Denmark)

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

    2014-01-01

    . MATERIAL AND METHODS: Participants in three international HIV trials (SMART, ESPRIT and SILCAAT) with IL-6 plasma levels measured at baseline were included (N=9864). Factors independently associated with log2-transformed IL-6 level were identified by multivariate linear regression; exponentiated estimates......INTRODUCTION: Elevated IL-6 levels have been linked to increased risk of cardiovascular disease (CVD), cancer and death. Compared to the general population, treated HIV+ persons have 50-100% higher IL-6 levels, but few data on the determinants of IL-6 levels during HIV infection currently exist...

  2. Observation on CEA and IL-6 contents in gastric juice

    International Nuclear Information System (INIS)

    Jiang Zhonglin

    2003-01-01

    Objective: To study the changes of CEA and IL-6 contents in blood and gastric juice in patients with gastric cancer and gastritis. Methods: CEA and IL-6 contents in blood and gastric juice were measured with RIA in 60 patients and 30 controls. Results: Gastric juice CEA and IL-6 contents in patients with gastric carcinoma were significantly higher than those in the controls (p < 0.001), however, CEA and IL-6 contents in patients with gastritis and controls were not much different. Conclusion: Gastric juice CEA and IL-6 assay is of diagnostic significance in patients with gastric malignant tumor

  3. IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling.

    Science.gov (United States)

    Timper, Katharina; Denson, Jesse Lee; Steculorum, Sophie Marie; Heilinger, Christian; Engström-Ruud, Linda; Wunderlich, Claudia Maria; Rose-John, Stefan; Wunderlich, F Thomas; Brüning, Jens Claus

    2017-04-11

    Interleukin (IL)-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R) expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH) of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling

    Directory of Open Access Journals (Sweden)

    Katharina Timper

    2017-04-01

    Full Text Available Interleukin (IL-6 engages similar signaling mechanisms to leptin. Here, we find that central ap