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Sample records for affect plasma cytokine

  1. Plasma cytokines in acute stroke

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Boysen, Gudrun; Christensen, Erik;

    2011-01-01

    months later plasma levels of interleukin 1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1RA), interleukin 6 (IL-6), interleukin 10 (IL-10), soluble tumor necrosis factor receptor 1 (sTNF-R1), and soluble tumor necrosis factor receptor 2 (sTNF-R2) were......GOALS: The aim of this study was to test the relations between plasma cytokines and the clinical characteristics, course, and risk factors in acute stroke. PATIENTS AND METHODS: The analysis was based on 179 patients with acute stroke included within 24 hours of stroke onset. On inclusion and 3...

  2. Cytokine plasma levels: reliable predictors for radiation pneumonitis?

    Directory of Open Access Journals (Sweden)

    Claudia E Rübe

    Full Text Available BACKGROUND: Radiotherapy (RT is the primary treatment modality for inoperable, locally advanced non-small-cell lung cancer (NSCLC, but even with highly conformal treatment planning, radiation pneumonitis (RP remains the most serious, dose-limiting complication. Previous clinical reports proposed that cytokine plasma levels measured during RT allow to estimate the individual risk of patients to develop RP. The identification of such cytokine risk profiles would facilitate tailoring radiotherapy to maximize treatment efficacy and to minimize radiation toxicity. However, cytokines are produced not only in normal lung tissue after irradiation, but are also over-expressed in tumour cells of NSCLC specimens. This tumour-derived cytokine production may influence circulating plasma levels in NSCLC patients. The aim of the present study was to investigate the prognostic value of TNF-alpha, IL-1beta, IL-6 and TGF-beta1 plasma levels to predict radiation pneumonitis and to evaluate the impact of tumour-derived cytokine production on circulating plasma levels in patients irradiated for NSCLC. METHODOLOGY/PRINCIPAL FINDINGS: In 52 NSCLC patients (stage I-III cytokine plasma levels were investigated by ELISA before and weekly during RT, during follow-up (1/3/6/9 months after RT, and at the onset of RP. Tumour biopsies were immunohistochemically stained for IL-6 and TGF-beta1, and immunoreactivity was quantified (grade 1-4. RP was evaluated according to LENT-SOMA scale. Tumour response was assessed according to RECIST criteria by chest-CT during follow-up. In our clinical study 21 out of 52 patients developed RP (grade I/II/III/IV: 11/3/6/1 patients. Unexpectedly, cytokine plasma levels measured before and during RT did not correlate with RP incidence. In most patients IL-6 and TGF-beta1 plasma levels were already elevated before RT and correlated significantly with the IL-6 and TGF-beta1 production in corresponding tumour biopsies. Moreover, IL-6 and TGF

  3. Plasma Cytokine Profiles in Long-Term Strenuous Exercise.

    Science.gov (United States)

    Nielsen, Hilde G; Øktedalen, Olav; Opstad, Per-Kristian; Lyberg, Torstein

    2016-01-01

    The open window theory indicates altered immunity 3 to 72 hours after exercise. The J-curve describes the risk of illness in response to exercise. The aim of this study was to examine the secretion of proinflammatory and anti-inflammatory cytokines before and after long-term strenuous exercise. Fourteen marathon and 16 half-marathon runners and 10 military cadets participating in a military ranger-training course were recruited to this study. Within-subject design was used measuring levels of plasma cytokines before, during, and after exercise. Plasma cytokines were measured using Luminex multiplex technology and ELISA. Comparing pre/post plasma levels both the marathon- and the half-marathon runners showed heavily increased levels of IL-6, IL-10, and IL-8 (P immune system is more activated and the subjects are more threatened to infectious pathogens after intensive physical activity and in the period after exercise. PMID:27239554

  4. Relationships Among Prenatal Depression, Plasma Cortisol, and Inflammatory Cytokines

    OpenAIRE

    Shelton, Melissa M.; Schminkey, Donna L.; Groer, Maureen W.

    2014-01-01

    A secondary pilot study was carried out as part of a larger parent study of thyroid function in pregnancy and postpartum. All women in the parent study (N = 631) had blood samples, demographic data, and measures of perceived stress and dysphoric moods collected between 16 and 26 weeks’ gestation. The current study was completed with a subset of 105 pregnant women to examine the relationships among perceived stress, depression, plasma cortisol and cytokines during the second trimester of pregn...

  5. Plasma Cytokine Profiles in Long-Term Strenuous Exercise

    Science.gov (United States)

    Nielsen, Hilde G.; Øktedalen, Olav; Opstad, Per-Kristian; Lyberg, Torstein

    2016-01-01

    The open window theory indicates altered immunity 3 to 72 hours after exercise. The J-curve describes the risk of illness in response to exercise. The aim of this study was to examine the secretion of proinflammatory and anti-inflammatory cytokines before and after long-term strenuous exercise. Fourteen marathon and 16 half-marathon runners and 10 military cadets participating in a military ranger-training course were recruited to this study. Within-subject design was used measuring levels of plasma cytokines before, during, and after exercise. Plasma cytokines were measured using Luminex multiplex technology and ELISA. Comparing pre/post plasma levels both the marathon- and the half-marathon runners showed heavily increased levels of IL-6, IL-10, and IL-8 (P < 0.001). LPS stimulation among the half-marathon runners decreased the postrace levels of IL-6, IL-1b, and TNFα by 45%, 24%, and 43%, respectively (P < 0.01). During the ranger training course the spontaneous and LPS-stimulated levels of IL-6, IL-8, IL-10, IL-1b, and TNFα changed in a similar fashion as in the half-marathon runners although the fluctuations were smaller. Our study supports the open window and the J-curve theory; the immune system is more activated and the subjects are more threatened to infectious pathogens after intensive physical activity and in the period after exercise.

  6. Intermittent preventive treatment with sulfadoxine-pyrimethamine does not modify plasma cytokines and chemokines or intracellular cytokine responses to Plasmodium falciparum in Mozambican Children

    Directory of Open Access Journals (Sweden)

    Quelhas Diana

    2012-01-01

    Full Text Available Abstract Background Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months. Results IPTi-SP did not significantly affect the proportion of CD3+ cells producing IFN-γ, IL-4 or IL-10. Overall, plasma cytokine or chemokine concentrations did not differ between treatment groups. Th1 and pro-inflammatory responses were higher than Th2 and anti-inflammatory responses, respectively, and IFN-γ:IL-4 ratios were higher for placebo than for SP recipients. Levels of cytokines and chemokines varied according to age, declining from 5 to 9 months. Plasma concentrations of IL-10, IL-12 and IL-13 were associated with current infection or prior malaria episodes. Higher frequencies of IFN-γ and IL-10 producing CD3+ cells and elevated IL-10, IFN-γ, MCP-1 and IL-13 in plasma were individually associated with increased malaria incidence, at different time points. When all markers were analyzed together, only higher IL-17 at 12 months was associated with lower incidence of malaria up to 24 months. Conclusions Our work has confirmed that IPTi-SP does not negatively affect the development of cellular immune response during early childhood. This study has also provided new insights as to how these cytokine responses are acquired upon age and exposure to P. falciparum, as well as their associations with malaria susceptibility. Trial Registration ClinicalTrials.gov: NCT00209795

  7. Plasma cytokine levels and risks of abdominal aortic aneurysms

    DEFF Research Database (Denmark)

    Liao, Mengyang; Liu, Cong-Lin; Lv, Bing-Jie; Zhang, Jin-Ying; Cheng, Longxian; Cheng, Xiang; Lindholt, Jes S; Rasmussen, Lars M; Shi, Guo-Ping

    2015-01-01

    BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell accumulation in AAA lesions that produce inflammatory cytokines and advance its pathogenesis. Peripheral cytokines may predict the degree or risk of AAA. METHODS AND RESULTS: ELISA determined plasma interleukin-6 (IL6......), IL10, IL17A, IFN-γ, and C-reactive protein (CRP) from 476 AAA patients and 200 controls. AAA patients had lower IL6, IFN-γ, IL10, IL17A, and higher CRP than controls. IL10 correlated positively with IFN-γ, IL17A, or IL6, but not CRP in control or AAA populations. IL10 associated negatively with...... systolic blood pressure, whereas CRP associated positively with diastolic blood pressure and body mass index. CRP was an independent AAA risk factor and correlated positively with aortic diameters before and after adjustments for other risk factors. IFN-γ, IL17A, and CRP correlated positively with cross...

  8. Exposure to Polycyclic Aromatic Hydrocarbons, Plasma Cytokines, and Heart Rate Variability

    OpenAIRE

    Binyao Yang; Qifei Deng; Wangzhen Zhang; Yingying Feng; Xiayun Dai; Wei Feng; Xiaosheng He; Suli Huang; Xiao Zhang; Xiaohai Li; Dafeng Lin; Meian He; Huan Guo; Huizhen Sun; Jing Yuan

    2016-01-01

    Epidemiological studies have suggested associations between polycyclic aromatic hydrocarbons (PAHs) and heart rate variability (HRV). However, the roles of plasma cytokines in these associations are limited. In discovery stage of this study, we used Human Cytokine Antibody Arrays to examine differences in the concentrations of 280 plasma cytokines between 8 coke-oven workers and 16 community residents. We identified 19 cytokines with significant different expression (fold change ≥2 or ≤−2, an...

  9. Aggressive periodontitis and chronic arthritis: blood mononuclear cell gene expression and plasma protein levels of cytokines and cytokine inhibitors

    DEFF Research Database (Denmark)

    Sørensen, Lars K; Havemose-Poulsen, Anne; Bendtzen, Klaus;

    2009-01-01

    BACKGROUND: Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti-inflammatory c......BACKGROUND: Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti.......001) or JIA (P = 0.002), and PBMC TNFA transcript levels were lower in patients with JIA (P = 0.001). A negative correlation was found between IL6 expression and IL-6 plasma levels in patients with JIA versus controls, and a positive correlation/association was found between TNFRI expression and s......TNF-RI plasma levels in patients with LAgP and RA. CONCLUSIONS: The study demonstrated only a few changes in the PBMC expression of various cytokine and cytokine inhibitor genes in aggressive periodontitis and chronic arthritis compared to controls. There were a few similarities among disease groups, and no...

  10. Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection

    Directory of Open Access Journals (Sweden)

    Hopkins Stephen J

    2012-11-01

    Full Text Available Abstract Background Cytokines and cytokine receptor concentrations increase in plasma and cerebrospinal fluid (CSF of patients following subarachnoid haemorrhage (SAH. The relationship between plasma and CSF cytokines, and factors affecting this, are not clear. Methods To help define the relationship, paired plasma and cerebrospinal fluid (CSF samples were collected from patients subject to ventriculostomy. Concentrations of key inflammatory cytokines, interleukin (IL-1ß, IL-1 receptor antagonist (IL-1Ra, IL-1 receptor 2, IL-6, IL-8, IL-10, tumour necrosis factor (TNF-α, and TNF receptors (TNF-R 1 and 2 were determined by immunoassay of CSF and plasma from 21 patients, where samples were available at three or more time points. Results Plasma concentrations of IL-1ß, IL-1Ra, IL-10, TNF-α and TNF-R1 were similar to those in CSF. Plasma TNF-R2 and IL-1R2 concentrations were higher than in CSF. Concentrations of IL-8 and IL-6 in CSF were approximately10 to 1,000-fold higher than in plasma. There was a weak correlation between CSF and plasma IL-8 concentrations (r = 0.26, but no correlation for IL-6. Differences between the central and peripheral pattern of IL-6 were associated with episodes of ventriculostomy-related infection (VRI. A VRI was associated with CSF IL-6 >10,000 pg/mL (P = 0.0002, although peripheral infection was not significantly associated with plasma IL-6. Conclusions These data suggest that plasma cytokine concentrations cannot be used to identify relative changes in the CSF, but that measurement of CSF IL-6 could provide a useful marker of VRI.

  11. Severe Traumatic Head Injury Affects Systemic Cytokine Expression

    Science.gov (United States)

    LaPar, Damien J; Rosenberger, Laura H; Walters, Dustin M; Hedrick, Traci L; Swenson, Brian R; Young, Jeffrey S; Dossett, Lesly A; May, Addison K; Sawyer, Robert G

    2012-01-01

    Background The neuroimmunologic effect of traumatic head injury remains ill-defined. This study aimed to characterize systemic cytokine profiles among traumatically injured patients to assess the effect of traumatic head injury on the systemic inflammatory response. Study Design Over five years, 1,022 patients were evaluated from a multi-institutional trauma immunomodulatory database (TIMD). Patients were stratified by presence of severe head injury (SHI, Head ISS ≥ 4, n=335) versus non-severe head injury (NHI, Head ISS ≤ 3, n=687). Systemic cytokine expression was quantified by ELISA within 72 hours of admission. Patient factors, outcomes, and cytokine profiles were compared by univariate analyses. Results SHI patients were more severely injured with higher mortality despite similar ICU infection and ventilator associated pneumonia (VAP) rates. Expression of early pro-inflammatory cytokines, IL-6 (p<0.001) and tumor necrosis factor (TNF)-α (p=0.02), were higher among NHI patients, while expression of immunomodulatory cytokines, interferon-γ (p=0.01) and IL-12 (p=0.003), was higher in SHI patients. High TNF-α levels in NHI patients were associated with mortality (p=0.01), increased mechanical ventilation (p=0.02), and development of VAP (p=0.01). Alternatively, among SHI patients, high IL-2 levels were associated with survival, decreased mechanical ventilation, and absence of VAP. Conclusions The presence of severe traumatic head injury significantly alters systemic cytokine expression and exerts an immunomodulatory effect. Early recognition of these profiles may allow for targeted intervention to reduce patient morbidity and mortality. PMID:22342787

  12. Do bacterial vaginosis and chlamydial infection affect serum cytokine level?

    Directory of Open Access Journals (Sweden)

    Bogavac Mirjana

    2010-01-01

    Full Text Available Introduction. Serbia is the country with extremely low birth rate and a relatively high percentage of preterm deliveries (8%. With this in mind, discovering new diagnostic methods that could be used for the prediction of preterm delivery is of great importance. In this study we tried to determine whether bacterial vaginosis and chlamydial infection could provoke preterm delivery by activation of systemic cytokine network. Objective. The aim of this study was to determine serum levels of proinflammatory cytokines (IL-1β, IL-8, IFN-γ, IL-6 and TNF-α in pregnant women with symptoms of preterm delivery and to make correlation between these parameters and the presence of bacterial vaginosis or chlamydial infection. Method. In the serum of 35 pregnant women, which were divided in groups according to the presence or absence of bacterial vaginosis and chlamydial infection, commercial ELISA tests for proinflammatory cytokines were performed. Results. The serum level of IFN-γ was significantly increased in pregnant women having chlamydial infection, as well as the level of IL-1β in women with bacterial vaginosis. The levels of TNF-α, IL-6 and IL-8 were not significantly different between the investigated groups. Conclusion. The preliminary results obtained in this research point out the possibility that not only intrauterine or systemic infections, but also bacterial vaginosis and chlamydial infection can cause a partial activation of systemic cytokine network and contribute to the occurrence of preterm delivery.

  13. Exposure to Polycyclic Aromatic Hydrocarbons, Plasma Cytokines, and Heart Rate Variability.

    Science.gov (United States)

    Yang, Binyao; Deng, Qifei; Zhang, Wangzhen; Feng, Yingying; Dai, Xiayun; Feng, Wei; He, Xiaosheng; Huang, Suli; Zhang, Xiao; Li, Xiaohai; Lin, Dafeng; He, Meian; Guo, Huan; Sun, Huizhen; Yuan, Jing; Lu, Jiachun; Hu, Frank B; Zhang, Xiaomin; Wu, Tangchun

    2016-01-01

    Epidemiological studies have suggested associations between polycyclic aromatic hydrocarbons (PAHs) and heart rate variability (HRV). However, the roles of plasma cytokines in these associations are limited. In discovery stage of this study, we used Human Cytokine Antibody Arrays to examine differences in the concentrations of 280 plasma cytokines between 8 coke-oven workers and 16 community residents. We identified 19 cytokines with significant different expression (fold change ≥2 or ≤-2, and q-value coke-oven workers by enzyme-linked immunosorbent assays in validation stage. We found OH-PAHs were inversely associated with brain-derived neurotrophic factor (BDNF) (p 16% BDNF decreases. Additionally, OH-PAHs were positively associated with activated leukocyte cell adhesion molecule (ALCAM) and C-reactive protein (CRP) (p 20% increases in CRP. We also found significant associations between these cytokines and HRV (p 8% decreases in HRV. Our results indicated PAH exposure was associated with plasma cytokines, and higher cytokines were associated with decreased HRV, but additional human and potential mechanistic studies are needed. PMID:26758679

  14. Cytokine, chemokine, and growth factor profile of platelet-rich plasma.

    Science.gov (United States)

    Mussano, F; Genova, T; Munaron, L; Petrillo, S; Erovigni, F; Carossa, S

    2016-07-01

    During wound healing, biologically active molecules are released from platelets. The rationale of using platelet-rich plasma (PRP) relies on the concentration of bioactive molecules and subsequent delivery to healing sites. These bioactive molecules have been seldom simultaneously quantified within the same PRP preparation. In the present study, the flexible Bio-Plex system was employed to assess the concentration of a large range of cytokines, chemokines, and growth factors in 16 healthy volunteers so as to determine whether significant baseline differences may be found. Besides IL-1b, IL-1ra, IL-4, IL-6, IL-8, IL-12, IL-13, IL-17, INF-γ, TNF-α, MCP-1, MIP-1a, RANTES, bFGF, PDGF, and VEGF that were already quantified elsewhere, the authors reported also on the presence of IL-2, IL-5, IL-7, IL-9, IL-10, IL-15 G-CSF, GM-CSF, Eotaxin, CXCL10 chemokine (IP-10), and MIP 1b. Among the most interesting results, it is convenient to mention the high concentrations of the HIV-suppressive and inflammatory cytokine RANTES and a statistically significant difference between males and females in the content of PDGF-BB. These data are consistent with previous reports pointing out that gender, diet, and test system affect the results of platelet function in healthy subjects, but seem contradictory when compared to other quantification assays in serum and plasma. The inconsistencies affecting the experimental results found in literature, along with the variability found in the content of bioactive molecules, urge further research, hopefully in form of randomized controlled clinical trials, in order to find definitive evidence of the efficacy of PRP treatment in various pathologic and regenerative conditions. PMID:26950533

  15. Systemic Inflammation Affects Human Osteocyte-Specific Protein and Cytokine Expression.

    Science.gov (United States)

    Pathak, Janak L; Bakker, Astrid D; Luyten, Frank P; Verschueren, Patrick; Lems, Willem F; Klein-Nulend, Jenneke; Bravenboer, Nathalie

    2016-06-01

    Bone remodeling can be disturbed in active rheumatoid arthritis (RA), possibly as a result of elevated levels of circulating inflammatory cytokines. Osteocyte-specific proteins and cytokines play a vital role in bone remodeling by orchestrating bone formation and/or bone resorption. Therefore, we aimed to investigate the effect of RA-serum or inflammatory cytokines on expression of human osteocyte-specific proteins and cytokines. Human trabecular bone chips were cultured with RA-serum or inflammatory cytokines for 7-days. Live-dead staining was performed to assess cell viability. Gene expression of osteocyte-specific proteins and cytokines was analyzed by qPCR. Immuno-staining was performed for osteocyte-specific markers. Approximately 60 % of the osteocytes on the bone chips were alive at day-7. Cells in or on the bone chips did express the gene for osteocyte markers SOST, FGF23, DMP1, and MEPE, and the cytokines IL-1β, IL-6, and TNFα at day 0 and 7. Active RA-serum treatment enhanced IL-1β, TNFα, SOST, and DKK1 gene expression. IL-1β treatment enhanced IL-1β, TNFα, IL-6, IL-8, FGF23, and SOST gene expression. TNFα treatment enhanced IL-1β, TNFα, IL-6, IL-8, and FGF23 gene expression. IL-8 treatment enhanced TNFα, IL-8, and FGF23 gene expression. A combination of IL-1β, IL-6, and TNFα treatment synergistically upregulated IL-1β, IL-6, and IL-8 gene expression, as well as enhanced TNFα, OPG, SOST, and FGF23, and inhibited DKK1 gene expression. In conclusion, gene expression of human osteocyte-specific proteins and cytokines was affected by RA-serum, and exogenous recombinant cytokines treatment suggesting that osteocytes could provide a new target to prevent systemic inflammation-induced bone loss in RA. PMID:26887974

  16. Obesity Related Alterations in Plasma Cytokines and Metabolic Hormones in Chimpanzees

    OpenAIRE

    2014-01-01

    Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, t...

  17. TLR-mediated NF-kB-dependent cytokine production is differently affected by HIV therapeutics

    DEFF Research Database (Denmark)

    Melchjorsen, Jesper; Paludan, Søren Riis; Mogensen, Trine; Tolstrup, Martin; Østergaard, Lars Jørgen

      Pathogen-recognizing Toll-like receptors 2 (TLR2) and TLR4 are known to recognize a number of pathogens, including E.Coli, S. Pneumonia and N. Meningococcus. We have studied whether a number of HIV therapeutics affect immediate proinflammatory cytokine responses in cell cultures. Preliminary...... results suggest an opposing effect of the drugs Tenofovir and Retrovir (AZT) on TLR-mediated production of NF-kappaB-dependent proinflammatory cytokines. We present data on the mechanisms behind the drug-mediated remodeling of innate immune activation and how the drugs effect early host...

  18. The effects of age and gender on plasma levels of 63 cytokines.

    Science.gov (United States)

    Larsson, Anders; Carlsson, Lena; Gordh, Torsten; Lind, Anne-Li; Thulin, Måns; Kamali-Moghaddam, Masood

    2015-10-01

    Cytokines play important roles as regulators of cell functions, and over the last decades a number of cytokine assays have been developed. The aim of the present study was to investigate the effects of age and gender on a large number of cytokines. Plasma samples were collected from 33 healthy blood donors. The samples were analyzed using a multiplex proximity extension assay (PEA) allowing simultaneous measurement of 92 cytokines and four technical controls. Biomarkers with less than 80% quantitative results were excluded leaving 63 cytokines that were analyzed for the effects of gender and age. The plasma level of three of the investigated biomarkers (DNER, MCP-4 and MMP-10) were found to be significantly different for the two genders (adjusted p-valueCCL11, CCL25, CDCP1, CSF-1, CXCL11, CXCL9, FGF-23, Flt3L, HGF, IL-10RB, MCP-3, MCP-4, MMP-10, OPG, VEGF-A) were significantly associated with age. This study reveals the effects of age and gender on a large number of cytokine assays. CXCL5 and TNFB were significantly higher in females, while the other markers with significant gender-dependent differences were higher in males. For the markers that were significantly associated with age, only CXCL6 was found to decrease with age, while the other biomarkers increased with age. PMID:26080062

  19. Plasma cytokine levels in Tanzanian HIV-1-infected adults and the effect of antiretroviral treatment

    DEFF Research Database (Denmark)

    Haissman, J.M.; Vestergaard, L.S.; Sembuche, S.;

    2009-01-01

    OBJECTIVE: To evaluate the role immune activation leading to the production and circulation of cytokines has in the pathogenesis of HIV infection in sub-Saharan Africa and the effect of antiretroviral treatment (ART) on these parameters. METHODS: Plasma concentrations of tumor necrosis factor (TN...

  20. Cytokines, growth, and environment factors in bone marrow plasma of acute lymphoblastic leukemia pediatric patients

    Czech Academy of Sciences Publication Activity Database

    Kováč, M.; Vášková, M.; Petráčková, Denisa; Pelková, V.; Mejstříková, E.; Kalina, T.; Žaliová, M.

    2014-01-01

    Roč. 25, č. 1 (2014), s. 8-13. ISSN 1148-5493 R&D Projects: GA MZd NR9531 Institutional support: RVO:61388971 Keywords : pediatric acute lymphoblastic leukemia * bone marrow plasma * cytokine Subject RIV: CE - Biochemistry Impact factor: 1.960, year: 2014

  1. Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    OBJECTIVE: Approximately 30% of patients with depression fail to respond to a selective serotonin reuptake inhibitor (SSRI). Few studies have attempted to define these patients from a biological perspective. Studies suggest that overall patients with depression show increased production of proinflammatory cytokines. We examined pro- and anti-inflammatory cytokine levels in patients who were SSRI resistant. METHODS: Plasma concentrations of IL-6, IL-8, IL-10, TNF-alpha and sIL-6R were measured with enzyme linked immunosorbent assays (ELISA) in DSM-1V major depressives who were SSRI resistant, in formerly SSRI resistant patients currently euthymic and in healthy controls. RESULTS: Patients with SSRI-resistant depression had significantly higher production of the pro-inflammatory cytokines IL-6 (p=0.01) and TNF-alpha (p=0.004) compared to normal controls. Euthymic patients who were formerly SSRI resistant had proinflammatory cytokine levels which were similar to the healthy subject group. Anti-inflammatory cytokine levels did not differ across the 3 groups. CONCLUSION: Suppression of proinflammatory cytokines does not occur in depressed patients who fail to respond to SSRIs and is necessary for clinical recovery.

  2. Multiplex Immunoassay of Plasma Cytokine Levels in Men with Alcoholism and the Relationship to Psychiatric Assessments

    Science.gov (United States)

    Manzardo, Ann M.; Poje, Albert B.; Penick, Elizabeth C.; Butler, Merlin G.

    2016-01-01

    Chronic alcohol use alters adaptive immunity and cytokine activity influencing immunological and hormone responses, inflammation, and wound healing. Brain cytokine disturbances may impact neurological function, mood, cognition and traits related to alcoholism including impulsiveness. We examined the relationship between plasma cytokine levels and self-rated psychiatric symptoms in 40 adult males (mean age 51 ± 6 years; range 33–58 years) with current alcohol dependence and 30 control males (mean age 48 ± 6 years; range 40–58 years) with no history of alcoholism using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Log-transformed cytokine levels were analyzed for their relationship with the Symptom Checklist-90R (SCL-90R), Barratt Impulsivity Scales (BIS) and Alcoholism Severity Scale (ASS). Inflammatory cytokines (interferon γ-induced protein-10 (IP-10); monocyte chemoattractant protein-1 (MCP1); regulated on activation, normal T cell expressed and secreted (RANTES)) were significantly elevated in alcoholism compared to controls while bone marrow-derived hematopoietic cytokines and chemokines (granulocyte-colony stimulating factor (GCSF); soluble CD40 ligand (sCD40L); growth-related oncogene (GRO)) were significantly reduced. GRO and RANTES levels were positively correlated with BIS scales; and macrophage-derived chemokine (MDC) levels were positively correlated with SCL-90R scale scores (p phobia. The novel association between RANTES and GRO and impulsivity phenotype in alcoholism should be further investigated in alcoholism and psychiatric conditions with core impulsivity and anxiety phenotypes lending support for therapeutic intervention. PMID:27043532

  3. Obesity Related Alterations in Plasma Cytokines and Metabolic Hormones in Chimpanzees

    Directory of Open Access Journals (Sweden)

    Pramod Nehete

    2014-01-01

    Full Text Available Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, tumor necrosis factor, soluble CD40 ligand, and Interleukin-1β and anti-inflammatory TH-2 cytokines, Interleukin-4, Interleukin-RA, Interleukin-10, and Interleukin-13 in overweight and obese chimpanzees. We also observed increased levels of metabolic hormones glucagon-like-peptide-1, glucagon, connecting peptide, insulin, pancreatic peptide YY3–36, and leptin in the plasma of overweight and obese chimpanzees. Chemokine, eotaxin, fractalkine, and monocyte chemoattractant protein-1 were higher in lean compared to obese chimpanzees, while chemokine ligand 8 increased in plasma of obese chimpanzees. We also observed an obesity-related effect on immune function as demonstrated by lower mitogen induced proliferation, and natural killer activity and higher production of IFN-γ by PBMC in Elispot assay, These findings suggest that lean, overweight, and obese chimpanzees share circulating inflammatory cytokines and metabolic hormone levels with humans and that chimpanzees can serve as a useful animal model for human studies.

  4. Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

    Directory of Open Access Journals (Sweden)

    S.F. Fonseca

    2016-03-01

    Full Text Available Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H and 8 normotensive (N subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively. They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity. Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS levels and ferric reducing ability of plasma (FRAP. Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05, although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1 and lower TBARS (P<0.01 and FRAP (P<0.05 levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors, present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

  5. Cytokines and migraine: increase of IL-5 and IL-4 plasma levels.

    Science.gov (United States)

    Munno, I; Centonze, V; Marinaro, M; Bassi, A; Lacedra, G; Causarano, V; Nardelli, P; Cassiano, M A; Albano, O

    1998-06-01

    Thirty-two patients suffering from migraine without aura were assessed during in interictal period to evaluate the contribution of cytokines to the pathophysiology of migraine. To this end, plasma levels of IFN-gamma, IL-4, IL-5, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA) techniques. Plasma levels of both IFN-gamma and IL-10 were not increased in the patients and did not differ significantly from healthy controls. Of interest, we observed a strong increase of IL-5 levels in 84.3% as well as increased IL-4 levels in 37.5% of patients with migraine without aura. These results suggests a preferential enhancement of some Th2-type cytokines, and may support the growing arguments of an immunoallergic mechanism in the pathophysiology of migraine. PMID:9664752

  6. Docosahexaenoic diet supplementation, exercise and temperature affect cytokine production by lipopolysaccharide-stimulated mononuclear cells.

    Science.gov (United States)

    Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Batle, Juan Miguel; Tur, Josep Antoni; Pons, Antoni

    2016-09-01

    Acute exercise induces changes in peripheral mononuclear cells' (PBMCs) capabilities to produce cytokines. The aim was to investigate the effect of docosahexaenoic acid (DHA) diet supplementation on cytokine production, by lipopolysaccharide (LPS)-stimulated PBMCs after exercise, and the in vitro influence of temperature. Fifteen male soccer players were randomly assigned to a placebo or an experimental group. The experimental group consumed an almond-based beverage enriched with DHA (1.16 g DHA/day) for 8 weeks, whereas the placebo group consumed a similar non-enriched beverage. Blood samples were taken before and after the nutritional intervention in basal conditions and 2 h after acute exercise. Nutritional intervention significantly increased the DHA content in erythrocytes only in experimental group (from 34 ± 3.6 to 43 ± 3.6 nmols DHA/10(9) erythrocytes). Exercise significantly increased Toll-like receptor 4 (TLR4) in PBMCs but only in the placebo group (203 %). Exercise also significantly increased IL6, IL8, VEGF, INFγ, TNFα, IL1α, IL1β, MCP1, and EGG production rates by LPS-stimulated PBMCs, and this response was attenuated by DHA supplementation. Temperature but not DHA also affected the pattern of cytokine production increasing IL6, IL8, IL1β, and MCP1 synthesis. The higher change was evidenced in IL1β increasing the production rate at 39.5 °C from 3.19 ± 0.77 to 22.4 ± 6.1 pg/h 10(6) PBMC in placebo and from 2.36 ± 0.11 to 10.6 ± 0.38 pg/h 10(6) PBMC in the supplemented group. The profile of affected cytokines differs between temperature and exercise, suggesting a different PBMC activation pathway. DHA diet supplementation only attenuated cytokine production after exercise and not that induced by temperature. PMID:27139422

  7. Plasma Cytokine Concentrations in Workers Exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    NARCIS (Netherlands)

    Saberi Hosnijeh, F.; Boers, D.; Portengen, L.; Bueno-de-Mesquita, H.B.; Heederik, D.; Vermeulen, R.

    2012-01-01

    Objectives: Few epidemiological studies have studied the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on blood cytokine levels. In this study we investigated changes in plasma levels of a large panel of cytokines, chemokines, and growth factors among workers from a Dutch historical cohort oc

  8. Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas

    International Nuclear Information System (INIS)

    Recent studies suggest that bacterial endotoxins may be associated with various chronic diseases, including colorectal adenomas and cancer. Given the evidence linking inflammation and colorectal cancer, we sought to determine if plasma endotoxin concentrations are associated with indicators of systemic or local inflammation and colorectal adenomas. This cross-sectional study consisted of participants who underwent screening colonoscopies and included adenoma cases (n=138) and non-adenoma controls (n=324). Plasma concentrations of endotoxin were measured with Limulus Amebocyte Lysate (LAL) assay. We quantified concentrations of inflammatory cytokines, interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) in plasma by ELISA and mRNA expression levels in rectal mucosal biopsies by quantitative RT-PCR. Interleukin-17 was evaluated only in the rectal mucosa. Compared to subjects with low plasma endotoxin concentrations, those with higher concentrations were more likely to have adenomas (OR 1.4, 95% CI 1.0-2.1). Among subjects with adenomas, those with villous histology were more likely to have higher endotoxin concentrations (5.4 vs. 4.1EU/mL, p=0.05) and lower plasma IFN-γ (0 vs. 1.64 pg/mL, p=0.02) compared to those with only tubular adenomas. Cases showed a trend of having higher plasma TNF-α levels than controls (p=0.06), but none of the other plasma or rectal mucosal cytokine levels differed between cases and controls. Elevated mucosal IL-12 levels were associated with having multiple adenomas (p=0.04). Higher concentrations of plasma endotoxin predicted increased plasma IL-12 levels (OR 1.5, 95% CI 1.0-2.2) and rectal mucosal IL-12 (OR 1.9, 95% CI 1.0-3.7) and IL-17 gene expression (OR 2.2, 95% CI 1.0-4.6). These findings suggest that interactions between elevated plasma endotoxin concentrations and inflammatory cytokines may be relevant to the development of colorectal adenomas

  9. Creatinine and cytokines plasma levels related to HLA compatibility in kidney transplant patients

    Directory of Open Access Journals (Sweden)

    Lorraine V. Alves

    2015-10-01

    Full Text Available ABSTRACTIntroduction:The success of kidney transplantation depends on prevention of organ rejection by the recipient’s immune system, which recognizes alloantigens present in transplanted tissue. Human leukocyte antigen (HLA typing is one of the tests used in pre-renal transplantation and represents one of the most important factors for a successful procedure.Objective:The present study evaluated creatinine and cytokines plasma levels in kidney transplant patients according to pre-transplant HLA typing.Methods:We assessed 40 renal transplanted patients selected in two transplant centers in Belo Horizonte (MG.Results:Patients were distributed into three groups according to HLA compatibility and, through statistical analysis, the group with more than three matches (H3 was found to have significantly lower post-transplant creatinine levels, compared to groups with three or fewer matches (H2 and H1, respectively. The median plasma levels of cytokines interleukin 6 (IL-6, tumor necrosis factor alpha (TNF-α, and interleukin 10 (IL-10 were evaluated according to the number of matches. Pro-inflammatory cytokines (IL-6 and TNF-α were significantly higher in groups with lower HLA compatibility. On the other hand, the regulatory cytokine IL-10 had significantly higher plasma levels in the group with greater compatibility between donor and recipient.Conclusion:These findings allow us to infer that pre-transplant HLA typing of donors and recipients can influence post-transplant renal graft function and may contribute to the development and choice of new treatment strategies.

  10. Impact of HIV co-infection on plasma level of cytokines and chemokines of pulmonary tuberculosis patients

    OpenAIRE

    Mihret, Adane; Abebe, Markos; Bekele, Yonas; Aseffa, Abraham; Walzl, Gerhard; Howe, Rawleigh

    2014-01-01

    Background The immunologic environment during HIV/M. tuberculosis co-infection is characterized by cytokine and chemokine irregularities that have been shown to increase immune activation, viral replication, and T cell dysfunction. Methods We analysed ex vivo plasma samples from 17 HIV negative and 16 HIV pulmonary tuberculosis co infected cases using Luminex assay to see impact of HIV co-infection on plasma level of cytokines and chemokines of pulmonary tuberculosis patients before and after...

  11. Changes in plasma steroids and cytokines levels in betel chewing patients in Taiwan.

    Science.gov (United States)

    Hu, Sindy; Chen, Wen-Chyuan; Hwang, Guey-Shyang; Chen, Szu-Tah; Kuo, Song-Bor; Chen, Yifen; Idova, Galina; Wang, Shyi-Wu

    2016-07-01

    Betel nut is the second largest economic food product in Taiwan. In Southeast Asia, the habit of chewing betel nut seems to be highly correlated with oral submucous fibrosis and oral squamous cell carcinoma. Oral submucous fibrosis is characterized by abnormal accumulation of oral submucous collagen fibers and limitation of mouth opening. Although the mechanism responsible for tissue damage is still unknown, prolonged irritation caused by betel nut and tobacco is considered to be a major factor contributing to the pathogenesis of oral submucous fibrosis. The effect of betel nut chewing on immune system remains unknown. Present study aims to investigate the change of plasma hormones including cortisol, testosterone, and inflammatory cytokine concentrations in male chewing betel nut compared with normal subjects. Heparinized blood was obtained from control group (normal young+mid-aged individuals), betel nut-chewing, and oral cancer male subjects. The study was approved by the Ethics Committee of the Chang-Gung Memorial Hospital. Written informed consent was granted by the patients. Plasma cortisol and testosterone concentrations were detected by commercial enzyme-linked immunosorbent assay (ELISA). The inflammatory cytokines, including interleukin-1β (IL-1β), IL-15, tumor necrosis factor-α (TNF-α), were analyzed by ELISA with commercial monoclonal capture antibodies and polyclonal detection antibodies. The median concentrations of plasma IL-1β, IL-15, and TNF-α were 3.14pg/ml, 3.14pg/ml, and 6.85pg/ml, respectively, in patients with oral cancer, compared with median plasma IL-1β, IL-15, and TNF-α concentration of 2.64pg/ml, 5.86pg/ml, and 5.38pg/ml, respectively, in patients with betel nut-chewing habit. In contrast, the median concentrations of plasma IL-1β, IL-15, and TNF-α in mid-aged males (aged 30-50) were 7.00pg/ml, 10.64pg/ml, and 31.73pg/ml, respectively, compared with median plasma concentration of IL-1β, IL-15, and TNF-α of 4.48pg/ml, 33.36pg

  12. Food contaminant zearalenone and its metabolites affect cytokine synthesis and intestinal epithelial integrity of porcine cells.

    Science.gov (United States)

    Marin, Daniela E; Motiu, Monica; Taranu, Ionelia

    2015-06-01

    The intestinal epithelium is the first barrier against food contaminants. Zearalenone (ZEN) is an estrogenic mycotoxin that was identified as a common contaminant of cereal grains and food and feedstuffs. In the present study, we have investigated the in vitro effects of ZEN and some of its metabolites (α-ZOL, β-ZOL) in concentrations of 10-100 µM on a swine epithelial cell line: Intestinal porcine epithelial cells (IPEC-1). We demonstrated that both ZEN metabolites were more toxic for IPEC cells as resulted from the XTT test, while for doses lower than 10 µM, only β-ZOL showed a more pronounced cytotoxicity versus epithelial cells as resulted from neutral red assay. ZEN has no effect on TER values, while α-ZOL significantly decreased the TER values, starting with day 4 of treatment. β-ZOL had a dual effect, firstly it induced a significant increase of TER, and then, starting on day 6, it induced a dramatic decrease of TER values as compared with on day 0. Concerning the cytokine synthesis, our results showed that ZEN has a tendency to increase the synthesis of IL-8 and IL-10. By contrast, α- and β-ZOL decreased the expression of both IL-8 and IL-10, in a dose dependent manner. In conclusion, our results showed that ZEN and its metabolites differently affected porcine intestinal cell viability, transepithelial resistance and cytokine synthesis with important implication for gut health. PMID:26035492

  13. From the regulatory functions of B cells to the identification of cytokine-producing plasma cell subsets.

    Science.gov (United States)

    Dang, Van Duc; Hilgenberg, Ellen; Ries, Stefanie; Shen, Ping; Fillatreau, Simon

    2014-06-01

    B lymphocytes have a unique role as antibody-producing cells. Antibodies are key mediators of humoral immunity against infections, and are thought to account for the protection afforded by successful vaccines. B cells can also secrete cytokines and subsequently regulate immune responses mediated by T and innate cells. Remarkably, recent studies identified plasma blasts/plasma cells as the main types of activated B cells producing the cytokines interleukin (IL)-10, IL-35, tumor necrosis factor (TNF)-α, IL-17, and GM-CSF in various contexts in mice. Here, we discuss these observations, which suggest the existence of various subsets of plasma blast/plasma cells distinguishable through their cytokine expression pattern. PMID:24637161

  14. Plasma cytokine concentration changes induced by the antitumor agents dipterinyl calcium pentahydrate (DCP) and related calcium pterins.

    Science.gov (United States)

    Moheno, Phillip; Pfleiderer, Wolfgang; Fuchs, Dietmar

    2009-01-01

    Analysis of plasma cytokine concentration changes determined that oral dosing with the antitumor agent (1:4 mol:mol) calcium pterin (CaPterin) increased plasma IL-10, decreased plasma IL-6, and decreased plasma IFN-gamma concentrations in nude mice with MDA-MB-231 xenograph tumors [Moheno, P., Pfleiderer, W., Dipasquale, A.G., Rheingold, A.L., Fuchs, D., 2008. Cytokine and IDO metabolite changes effected by calcium pterin during inhibition of MDA-MB-231 xenograph tumors in nude mice. Int. J. Pharm. 355, 238-248]. A further analysis, reported here, of plasma cytokine concentration changes in nude mice with the same tumor xenographs treated with dipterinyl calcium pentahydrate (DCP), (1:2 mol:mol) calcium pterin, and CaCl(2).2H(2)O has been carried out. The measured cytokines included: IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-gamma, and TNF-alpha. The major preliminary findings from the analyses of these data are that (1) the overall relative tumor volumes for the treatments correlated significantly with a full study antitumor plasma cytokine pattern (fsAPCP), a composite measure consisting of decreased plasma IL-6 and increased IL-4 concentrations, and (2) DCP induces a significant threshold antitumor response strongly correlated to a derived DCP antitumor plasma cytokine pattern (DCP/APCP) consisting of plasma IL-12, IL-6, and IL-4 concentration changes. This DCP/APCP composite measure identifies plasma IL-12 concentration increases, plasma IL-6 concentration decreases, and plasma IL-4 concentration increases correlated to relative tumor volume decreases caused by DCP dosing. The finding that the novel calcium pterins and CaCl(2).2H(2)O treatments decrease plasma IL-6 concentrations corroborates the previous finding that CaPterin dosing decreases plasma IL-6 concentrations in this mouse/tumor system [Moheno, P., Pfleiderer, W., Dipasquale, A.G., Rheingold, A.L., Fuchs, D., 2008. Cytokine and IDO metabolite changes effected by calcium pterin during inhibition

  15. Plasma cytokine levels fall in preterm newborn infants on nasal CPAP with early respiratory distress.

    Directory of Open Access Journals (Sweden)

    Clarissa Gutierrez Carvalho

    Full Text Available Early nCPAP seems to prevent ventilator-induced lung injury in humans, although the pathophysiological mechanisms underlying this beneficial effect have not been clarified yet.To evaluate plasma levels IL-1β, IL-6, IL-8, IL-10, and TNF-α immediately before the start of nCPAP and 2 hours later in preterm infants.Prospective cohort including preterm infants with 28 to 35 weeks gestational age with moderate respiratory distress requiring nCPAP. Extreme preemies, newborns with malformations, congenital infections, sepsis, surfactant treatment, and receiving ventilatory support in the delivery room were excluded. Blood samples were collected right before and 2 hours after the start of nCPAP.23 preterm infants (birth weight 1851±403 grams; GA 32.3±1.7 weeks were treated with nCPAP. IL-1β, IL-10, TNF-α levels were similar, IL-8 levels were reduced in 18/23 preterm infants and a significant decrease in IL-6 levels was observed after 2 hours of nCPAP. All newborns whose mothers received antenatal steroids had lower cytokine levels at the onset of nCPAP than those whose mothers didn't receive it; this effect was not sustained after 2 hours of nCPAP.Early use nCPAP is not associated with rising of plasma pro-inflammatory cytokines and it seems to be a less harmful respiratory strategy for preterm with moderate respiratory distress.

  16. Influence of poly I:C on sickness behaviors, plasma cytokines, corticosterone and central monoamine activity: moderation by social stressors.

    Science.gov (United States)

    Gandhi, Reno; Hayley, Shawn; Gibb, Julie; Merali, Zul; Anisman, Hymie

    2007-05-01

    Stressor and cytokine challenges provoke several common effects, and may synergistically influence behavioral and neurochemical functioning. In the present investigation, we assessed whether the effects of poly I:C would be influenced when administered on a backdrop of a psychosocial stressor. In naïve mice, poly I:C (2mg/kg) modestly increased sickness behaviors, plasma IL-6, TNF-alpha and IL-10 levels, but did not affect IL-1, IL-4, or IFN-gamma. The viral analogue also increased plasma corticosterone levels and norepinephrine (NE) utilization within the paraventricular hypothalamus (PVN) and hippocampus. However, among mice that had experienced social disruption (comprising 14 days of isolation followed by regrouping), the behavioral, IL-6, IL-10, and corticoid alterations provoked by poly I:C were markedly augmented. Moreover, following social disruption the effect of poly I:C on NE utilization was increased within the PVN, prefrontal cortex and central amygdala, as was serotonin utilization within the hippocampus. The effects of poly I:C were likewise augmented following social disruption engendered by introducing mice to strangers.. However, among mice that had previously been exposed to a chronic, variable psychosocial stressor regimen, the augmented behavioral, neuroendocrine and monoamine effects of poly I:C were absent, and IL-6 and IL-10 levels were reduced relative to mice that had not been chronically stressed. In contrast, levels of IL-1 beta and IFN-gamma were increased. Mechanisms that might be responsible for the interactive effects of social disruption and immune activation are presented, and the data were related to depressive symptoms associated with stressor and cytokine treatments. PMID:17267173

  17. Infusion of hypertonic saline before elective hysterectomy: effects on cytokines and stress hormones

    DEFF Research Database (Denmark)

    Kolsen-Petersen, J A; Bendtzen, K; Tonnesen, E

    2008-01-01

    Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery.......Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery....

  18. Cytokine polymorphisms and plasma levels are associated with sleep onset insomnia in adults living with HIV/AIDS.

    Science.gov (United States)

    Gay, Caryl L; Zak, Rochelle S; Lerdal, Anners; Pullinger, Clive R; Aouizerat, Bradley E; Lee, Kathryn A

    2015-07-01

    Sleep disturbance has been associated with inflammation and cytokine activity, and we previously described genetic associations between cytokine polymorphisms and sleep maintenance and duration among adults with HIV/AIDS. Although sleep onset insomnia (SOI) is also a commonly reported sleep problem, associations between cytokine biomarkers and SOI have not been adequately studied. The purpose of this study was to describe SOI in relation to cytokine plasma concentrations and gene polymorphisms in a convenience sample of 307 adults (212 men, 72 women, and 23 transgender) living with HIV/AIDS. Based on the Pittsburgh Sleep Quality Index item that asks the time it usually took to fall asleep in the past month, participants were categorized as either >30min to fall asleep (n=70, 23%) or 30min or less to fall asleep (n=237). Plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor alpha (TNFA). Demographic and clinical variables were evaluated as potential covariates. After adjusting for genomic estimates of ancestry, self-reported race/ethnicity and viral load, SOI was associated with higher IL-13 plasma levels and with six single nucleotide polymorphisms (SNPs): IL1B rs1143642 and rs1143623, IL6 rs4719714, IL13 rs1295686, NFKB1 rs4648110, and TNFA rs2857602. In addition, the IL1B rs1143642 polymorphism was associated with plasma levels of IL-1β in adjusted analyses. This study strengthens the evidence for an association between inflammation and sleep disturbance, particularly self-report of habitual SOI. In this chronic illness population, the cytokine polymorphisms associated with SOI provide direction for future personalized medicine intervention research. PMID:25535857

  19. Cytokine-mediated regulation of plasma cell generation: IL-21 takes center stage

    Directory of Open Access Journals (Sweden)

    Stuart G Tangye

    2014-02-01

    Full Text Available During our life we are surrounded by continuous threats from a diverse range of invading pathogens. Our immune system has evolved multiple mechanisms to efficiently deal with these threats to prevent them causing disease. Differentiation of mature B cells into plasma cells (PC - the antibody (Ab secreting cells of the immune system - is critical for the generation of protective and long-lived humoral immune responses. Indeed, efficient production of antigen (Ag-specific Ab underlies the success of most currently available vaccines. The mature B cell pool is composed of several subsets, distinguished from one according to size, surface marker expression, location and Ag exposure, and they all have the capacity to differentiate into PCs. For a B cell to acquire the capacity to produce Abs, it must undergo an extensive differentiation process driven by changes in gene expression. Two broad categories of Ag exist that cause B cell activation and differentiation: T cell dependent (TD or T cell independent (TI. In addition to the B cell subset and nature of the Ag, it is important to consider the cytokine environment that also influences how B cell differentiation is achieved. Thus, while many cytokines can induce Ab secretion by B cells after activation with mimics of TD and TI stimuli in vitro, they can have different efficacies and specificities, and can often preferentially induce production of one Ig isotype over another. Here, we will provide an overview of in vitro studies (mouse and human origin that evaluated the role the different cytokines in inducing the differentiation of distinct B cell subsets to the PC lineage. We will place particular emphasis on IL-21, which has emerged as the most potent inducer of terminal B cell differentiation in humans. We will also focus on the role of IL-21 and defects in B-cell function and how these contribute to human immunopathologies such as primary immunodeficiencies and B-cell mediated autoimmune

  20. Plasma Cytokine Concentrations Indicate In-vivo Hormonal Regulation of Immunity is Altered During Long-Duration Spaceflight

    Science.gov (United States)

    Crician, Brian E.; Zwart, Sara R.; Mehta, Satish; Uchakin, Peter; Quiriarte, Heather A.; Pierson, Duane; Sams, Clarence F.; Smith, Scott M.

    2013-01-01

    Background: Aspects of immune system dysregulation associated with long-duration spaceflight have yet to be fully characterized, and may represent a clinical risk to crewmembers during deep space missions. Plasma cytokine concentration may serve as an indicator of in vivo physiological changes or immune system mobilization. Methods: The plasma concentrations of 22 cytokines were monitored in 28 astronauts during long-duration spaceflight onboard the International Space Station. Blood samples were collected three times before flight, 3-5 times during flight (depending on mission duration), at landing and 30 days post-landing. Analysis was performed by bead array immunoassay. Results: With few exceptions, minimal detectable mean plasma levels (plasma concentration IL-8, IL-1ra, Tpo, CCL4, CXCL5, TNF(alpha), GM-CSF and VEGF was observed associated with spaceflight. Significant post-flight increases were observed for IL-6 and CCL2. No significant alterations were observed during or following spaceflight for adaptive/T-regulatory cytokines (IL-2, IFN(gamma), IL-17, IL4, IL-5, IL-10). Conclusions: This pattern of cytokine dysregulation suggests multiple physiological adaptations persist during flight, including inflammation, leukocyte recruitment, angiogenesis and thrombocyte regulation.

  1. Trichuris suis ova therapy for allergic rhinitis does not affect allergen-specific cytokine responses despite a parasite-specific cytokine response

    DEFF Research Database (Denmark)

    Bourke, C.D.; Mutapi, F.; Nausch, N.;

    2012-01-01

    Parasitic helminths have been shown to reduce inflammation in most experimental models of allergic disease, and this effect is mediated via cytokine responses. However, in humans, the effects of controlled helminth infection on cytokine responses during allergy have not been studied.......Parasitic helminths have been shown to reduce inflammation in most experimental models of allergic disease, and this effect is mediated via cytokine responses. However, in humans, the effects of controlled helminth infection on cytokine responses during allergy have not been studied....

  2. Acute-phase proteins, oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin in Arabian mares affected with pyometra.

    Science.gov (United States)

    El-Bahr, S M; El-Deeb, W M

    2016-09-01

    New biomarkers are essential for diagnosis of pyometra in mares. In this context, 12 subfertile Arabian mares suffered from pyometra were admitted to the Veterinary Teaching Hospital. The basis for diagnosis of pyometra was positive findings of clinical examination and rectal palpation. Blood samples were collected from diseased animals and from five Arabian healthy mares, which were considered as control group. Acute-phase proteins (APP), oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin I were estimated in the harvested sera of both groups. Clinical examination revealed purulent yellowish fluid discharged from vagina of affected animals and rectal palpation of the reproductive tract revealed uterine distention. The biochemical analysis of the serum revealed significant increase in cardiac troponin I, creatin kinase, alkaline phosphatase, malondialdehyde, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin, and serum amyloid A and significant decrease in reduced glutathione, superoxide dismutase (SOD), total antioxidant capacity, and nitric oxide (NO) of mares affected with pyometra compare to control. Cardiac troponin I was positively correlated with aspartate aminotransferase, creatin kinase, malondialdehyde, alkaline phosphatase, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin and serum amyloid A and negatively correlated with glutathione, superoxide dismutase, total antioxidant capacity and nitric oxide in serum of mares affected with pyometra. Moreover, there was high positive correlation between proinflammatory cytokines and APP in serum of mares affected with pyometra. The present study suggests cardiac troponin I together with APP, proinflammatory cytokines, and oxidative stress parameters as biomarkers for pyometra in Arabian mares. PMID:27177966

  3. Plasma levels of inflammatory cytokines in adult Nigerians with the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Udenze Ifeoma Christiana

    2016-01-01

    Full Text Available Background: The aim of this study is to determine the plasma levels of interleukin 6 (IL-6, tumor necrotic factor alpha (TNF-α, and C-reactive protein (CRP in adult Nigerians with the metabolic syndrome and to determine the relationship between components of the metabolic syndrome and CRP in adult Nigerians. Subjects and Methods: This was a case–control study of fifty adult men and women with the metabolic syndrome, and fifty age- and sex-matched males and females without the metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Programme-Adult Treatment Panel III criteria. Written informed consent was obtained from the participants. Blood pressure and anthropometry measurements were taken and venous blood was collected after an overnight fast. The Ethics Committee of the Lagos University Teaching Hospital, Lagos, Nigeria, approved the study protocol. Comparisons of continuous variables and categorical variables were done using the Student's t-test and Chi-square test, respectively. Regression analysis was used to determine the associations between variables. Statistical significance was set at P< 0.05. Results: The age- and sex-matched males and females with and without the metabolic syndrome did not differ in their sociodemographic characteristics. They however differed in some clinical and laboratory parameters such as diastolic blood pressure (P = 0.048, waist circumference (P = 0.002, body mass index (P = 0.012, waist/hip ratio (P = 0.023, high density lipoprotein (HDL (P = 0.012, and insulin resistance (IR (P = 0.042. There was a statistically significant increase in the inflammatory marker, CRP (P = 0.019, the cytokines, IL6 (P = 0.040, and TNF-α (P = 0.031 between the subjects with and without metabolic syndrome. There was also a significant association between CRP, waist circumference, IR, and HDL in the metabolic syndrome (P < 0.05. Conclusion: Plasma levels of inflammatory cytokines are

  4. Clove (Syzygium aromaticum ingredients affect lymphocyte subtypes expansion and cytokine profile responses: An in vitro evaluation

    Directory of Open Access Journals (Sweden)

    Shaghayegh Pishkhan Dibazar

    2014-12-01

    Full Text Available Clove (Syzygium aromaticum has been used in folk medicine in many disorders. The present work aimed to investigate effects of clove essential oil as eugenol and water soluble ingredients on mouse splenocytes. Clove extracts were harvested and in different concentrations (0.001–1000 μg/mL were affected to splenocytes and also phytohemagglutinin (PHA = 5 μg/mL and lipopolysaccharide (LPS = 10 μg/mL activated splenocytes; then splenocytes proliferation assayed using the MTT ([3-(4, 5-dimethylthiazole-2-yl -2, 5-diphenyl tetrazolium bromide] method were done. On the culture supernatant interferon (IFN-γ, interleukin (IL-4, IL-10, and transforming growth factor (TGF-β cytokines were measured. Clove ingredients (100 μg/mL and 1000 μg/mL reduced PHA stimulated splenocytes proliferation and enhanced LPS stimulated cells expansion. Treated splenocytes showed suppression of IFN-γ release and induction of IL-4, IL-10, and TGF-β secretion (in the range of 0.1–1000 μg/mL. The results of this study suggest clove extracts could suppress the T cell cellular immunity and enhance humoral immune responses. In clove affection cytokine pattern shifted toward modulatory and Th2 responses and accelerator of humoral immunity cytokines.

  5. Environmental Levels of para-Nonylphenol Are Able to Affect Cytokine Secretion in Human Placenta

    OpenAIRE

    Bechi, Nicoletta; Ietta, Francesca; Romagnoli, Roberta; Jantra, Silke; Cencini, Marco; Galassi, Gianmichele; Serchi, Tommaso; Corsi, Ilaria; Focardi, Silvano; Paulesu, Luana

    2009-01-01

    Background para-Nonylphenol (p-NP) is a metabolite of alkylphenols widely used in the chemical industry and manufacturing. It accumulates in the environment, where it acts with estrogen-like activity. We previously showed that p-NP acts on human placenta by inducing trophoblast differentiation and apoptosis. Objective The aim of the present study was to investigate the effect of p-NP on cytokine secretion in human placenta. Methods In vitro cultures of chorionic villous explants from human pl...

  6. Impact of gender and menstrual cycle phase on plasma cytokine concentrations.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    OBJECTIVE: The lifetime prevalence of major depression is twice as high in females as in males. Depression is known to increase at periods where there are changes in gonadal hormones. We examined pro- and anti-inflammatory cytokine levels during the normal menstrual cycle of healthy females compared to similar time points in healthy males. METHODS: Plasma concentrations of interleukin (IL)-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-alpha) and soluble IL-6 receptor (sIL-6R) were measured with enzyme-linked immunosorbent assays in healthy females during the normal ovulatory menstrual cycle and also in males at similar time points. RESULTS: The luteal phase of the menstrual cycle is associated with increased production of sIL-6R, IL-4 and TNF-alpha compared to the early follicular phase. No change was observed in IL-6, IL-8 and IL-10 concentration throughout the menstrual cycle. We found IL-4 positively correlated with oestrogen while TNF-alpha positively correlated with progesterone. Females were found to have significantly higher concentrations of TNF-alpha and sIL-6R across all phases of the menstrual cycle, compared to males across similar time points. CONCLUSION: The normal menstrual cycle is associated with increased production of sIL-6R, IL-4 and TNF-alpha in the luteal phase compared to the early follicular phase. Females have significantly higher concentrations of sIL-6R and TNF-alpha at all time points across the menstrual cycle than males.

  7. Blood sampling and hemolysis affect concentration of plasma metabolites

    DEFF Research Database (Denmark)

    Theil, Peter Kappel; Pedersen, Lene Juul; Jensen, Margit Bak;

    2012-01-01

    Two experiments were carried out to reveal and quantify plasma metabolites that are sensitive to hemolysis and animal stress due to the blood sampling procedure (vein puncture vs. catheter). In Exp. 1, 48 sows were fed 4 diets either once (0800 h) or twice daily (0800 h and 1500 h) in a crossover...... design and blood was collected after restraint via vein puncture 1, 4, 11, and 23 h after morning feeding. Plasma samples were categorized as without or with minor or major hemolysis [clear (n = 218), yellow (n = 97), or red (n = 37)] upon centrifugation. Plasma NEFA (P < 0.001) was lower in hemolyzed...... samples but plasma propionate, caproate, isovalerate (P < 0.001), and isobutyrate (P < 0.05) were higher in hemolyzed samples. Plasma glucose and lactate were the only metabolites that were not affected by hemolysis. Interactions with hemolysis and other fixed effects were not found (P > 0.05). In Exp. 2...

  8. Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-gamma during the isolation of the Antarctic winter

    Science.gov (United States)

    Shearer, William T.; Lee, Bang-Ning; Cron, Stanley G.; Rosenblatt, Howard M.; Smith, E. O'Brian; Lugg, Desmond J.; Nickolls, Peter M.; Sharp, Robert M.; Rollings, Karl; Reuben, James M.

    2002-01-01

    Cellular immune function has been shown to be decreased and latent virus shedding to be increased in human beings isolated during the Antarctic winter, a model used for assessing some effects of space flight. However, the balance of proinflammatory (IFN-gamma) and anti-inflammatory (IL-10 and IL-1RA) cytokines has not previously been evaluated. We therefore sought to determine whether isolation during the Antarctic winter would alter the proinflammatory and anti-inflammatory cytokine balance. Cytokine levels were measured with ELISA in monthly plasma samples from January through September 1999 in 21 study subjects in the Antarctic and 7 control subjects on Macquarie Island. There was a significant time-dependent increase in plasma IFN-gamma (P =.039) as well as decreases in IL-10 (P =.042) and IL-1RA (P =.053) in the study subjects compared with the control subjects. The study subjects also had significantly increased plasma IFN-gamma levels (P < or =.045) but decreased IL-10 and IL-1RA levels (P < or =.036) at individual time points of isolation. Isolation of human beings in the Antarctic appears to shift the plasma cytokine balance toward a proinflammatory profile. These observations are consistent with T-cell activation that might be due to activation of latent viruses, and they could hold importance for determining the risks of space flight.

  9. Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women.

    Directory of Open Access Journals (Sweden)

    Pascale Ondoa

    Full Text Available Genital viral load (GVL is the main determinant of sexual transmission of human immune-deficiency virus (HIV. The effect of antiretroviral therapy (ART on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda.All participants were evaluated for GVL, plasma viral load (PVL, CD4 count, various sexually-transmitted infections (STIs at baseline and at month 12. Genital concentration of 19 cytokines and mRNA expression of APOBEC3G and BST2, two host HIV restriction factors, were evaluated at baseline in all participants. Cytokine levels were re-assessed at month 12 only in participants eligible for ART at baseline. Risk factors of GVL ≥ 40 copies/mL at baseline and month 12 were assessed using logistic regression. Effect of 12-month ART on various local and systemic immunological parameters was examined using a paired t-test and McNemar as appropriate.96 of the 247 women enrolled in the study were eligible for ART. After 12 months of ART, PVL and GVL decreased to undetectable level in respectively 74 and 88% of treated participants. ART did not affect cytokine levels. HIV genital shedding occurred only when PVL was detectable. At baseline, GVL was independently associated with IL-1β after controlling for PVL, age and N. gonorrhea infection (95% CI 1.32-2.15 and at month 12 with MIP-1β (95% CI 0.96-21.32 after controlling for baseline GVL, PVL and month 12 IL-8.Suppressive ART does not necessarily reduce genital level of immune activation. Minimizing all conditions favoring genital inflammation, including active detection and treatment of STIs, might reduce the risk of HIV transmission as supplement to the provision of potent ART.

  10. Anticoagulants used in plasma collection affect adipokine multiplexed measurements.

    Science.gov (United States)

    Allione, Alessandra; Di Gaetano, Cornelia; Dani, Nadia; Barberio, Davide; Sieri, Sabina; Krogh, Vittorio; Matullo, Giuseppe

    2016-04-01

    Obesity is an important health problem worldwide. Adipose tissue acts as an endocrine organ that secretes various bioactive substances, called adipokines, including pro-inflammatory biomarkers such as TNF-α, IL-6, leptin and C-reactive protein (CRP) and anti-inflammatory molecules such as adiponectin. The deregulated production of adipokines in obesity is linked to the pathogenesis of various disease processes and monitoring their variation is critical to understand metabolic diseases. The aim of this study was to determine the plasma concentration of adipokines in healthy subjects by multiplexed measurements and the effect of anticoagulants on their levels. Plasma samples from 10 healthy donors were collected in two different anticoagulants (sodium citrate or heparin). All markers, excluding TNF-α, showed significantly higher concentrations in heparinized compared to citrate plasma. However, levels of adipokines in different plasma samples were highly correlated for most of these markers. We reported that different anticoagulants used in the preparation of the plasma samples affected the measurements of some adipokines. The importance of the present results in epidemiology is relevant when comparing different studies in which blood samples were collected with different anticoagulants. PMID:26945995

  11. Intestinal Parasites Coinfection Does Not Alter Plasma Cytokines Profile Elicited in Acute Malaria in Subjects from Endemic Area of Brazil

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    Juan Camilo Sánchez-Arcila

    2014-01-01

    Full Text Available In Brazil, malaria is prevalent in the Amazon region and these regions coincide with high prevalence of intestinal parasites but few studies explore the interaction between malaria and other parasites. Therefore, the present study evaluates changes in cytokine, chemokine, C-reactive protein, and nitric oxide (NO concentrations in 264 individuals, comparing plasma from infected individuals with concurrent malaria and intestinal parasites to individuals with either malaria infection alone and uninfected. In the studied population 24% of the individuals were infected with Plasmodium and 18% coinfected with intestinal parasites. Protozoan parasites comprised the bulk of the intestinal parasites infections and subjects infected with intestinal parasites were more likely to have malaria. The use of principal component analysis and cluster analysis associated increased levels of IL-6, TNF-α, IL-10, and CRP and low levels of IL-17A predominantly with individuals with malaria alone and coinfected individuals. In contrast, low levels of almost all inflammatory mediators were associated predominantly with individuals uninfected while increased levels of IL-17A were associated predominantly with individuals with intestinal parasites only. In conclusion, our data suggest that, in our population, the infection with intestinal parasites (mainly protozoan does not modify the pattern of cytokine production in individuals infected with P. falciparum and P. vivax.

  12. Vaccenic and Elaidic Acid Modify Plasma and Splenocyte Membrane Phospholipids and Mitogen-Stimulated Cytokine Production in Obese Insulin Resistant JCR: LA-cp Rats

    Directory of Open Access Journals (Sweden)

    Donna F. Vine

    2010-02-01

    Full Text Available This study assessed the long-term effects of dietary vaccenic acid (VA and elaidic acid (EA on plasma and splenocyte phospholipid (PL composition and related changes in inflammation and splenocyte phenotypes and cytokine responses in obese/insulin resistant JCR:LA-cp rats. Relative to lean control (Ctl, obese Ctl rats had higher serum haptoglobin and impaired T-cell-stimulated cytokine responses. VA and EA diets improved T-cell-stimulated cytokine production; but, only VA normalized serum haptoglobin. However, EA- and VA-fed rats had enhanced LPS-stimulated cytokine responses. The changes elicited by VA were likely due changes in essential fatty acid composition in PL; whereas EA-induced changes may due to direct incorporation into membrane PL.

  13. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology

    Science.gov (United States)

    Tenzer, Stefan; Docter, Dominic; Kuharev, Jörg; Musyanovych, Anna; Fetz, Verena; Hecht, Rouven; Schlenk, Florian; Fischer, Dagmar; Kiouptsi, Klytaimnistra; Reinhardt, Christoph; Landfester, Katharina; Schild, Hansjörg; Maskos, Michael; Knauer, Shirley K.; Stauber, Roland H.

    2013-10-01

    In biological fluids, proteins bind to the surface of nanoparticles to form a coating known as the protein corona, which can critically affect the interaction of the nanoparticles with living systems. As physiological systems are highly dynamic, it is important to obtain a time-resolved knowledge of protein-corona formation, development and biological relevancy. Here we show that label-free snapshot proteomics can be used to obtain quantitative time-resolved profiles of human plasma coronas formed on silica and polystyrene nanoparticles of various size and surface functionalization. Complex time- and nanoparticle-specific coronas, which comprise almost 300 different proteins, were found to form rapidly (<0.5 minutes) and, over time, to change significantly in terms of the amount of bound protein, but not in composition. Rapid corona formation is found to affect haemolysis, thrombocyte activation, nanoparticle uptake and endothelial cell death at an early exposure time.

  14. Plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Noone Cariosa

    2013-01-01

    Full Text Available Abstract Background Malaria is a major cause of morbidity and mortality worldwide with over one million deaths annually, particularly in children under five years. This study was the first to examine plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum from four semi-urban villages near Ile-Ife, Osun State, Nigeria. Methods Blood was obtained from 231 children (aged 39–73 months who were classified according to mean P. falciparum density per μl of blood (uninfected (n = 89, low density (10,000, n = 22. IL-12p70, IL-10, Nitric oxide, IFN-γ, TNF, IL-17, IL-4 and TGF-β, C-C chemokine RANTES, MMP-8 and TIMP-1 were measured in plasma. Peripheral blood mononuclear cells were obtained and examined markers of innate immune cells (CD14, CD36, CD56, CD54, CD11c AND HLA-DR. T-cell sub-populations (CD4, CD3 and γδTCR were intracellularly stained for IL-10, IFN-γ and TNF following polyclonal stimulation or stimulated with malaria parasites. Ascaris lumbricoides was endemic in these villages and all data were analysed taking into account the potential impact of bystander helminth infection. All data were analysed using SPSS 15 for windows and in all tests, p Results The level of P. falciparum parasitaemia was positively associated with plasma IL-10 and negatively associated with IL-12p70. The percentage of monocytes was significantly decreased in malaria-infected individuals while malaria parasitaemia was positively associated with increasing percentages of CD54+, CD11c+ and CD56+ cell populations. No association was observed in cytokine expression in mitogen-activated T-cell populations between groups and no malaria specific immune responses were detected. Although A. lumbricoides is endemic in these villages, an analysis of the data showed no impact of this helminth infection on P. falciparum parasitaemia or on immune responses associated with P. falciparum infection

  15. Growth/differentiation factor-I5 is an abundant cytokine in human seminal plasma

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Slabáková, Eva; Ovesná, P.; Malenovská, A.; Kozubík, Alois; Hampl, Aleš

    2010-01-01

    Roč. 25, č. 12 (2010), s. 2962-2971. ISSN 0268-1161 R&D Projects: GA MZd NS9600 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390703 Keywords : seminal plasma * growth/differentiation factor-15 (GDF-15/MIC-1) * FOXP3 Subject RIV: BO - Biophysics Impact factor: 4.357, year: 2010

  16. Influence of Hydration Status on Changes in Plasma Cortisol, Leukocytes, and Antigen-Stimulated Cytokine Production by Whole Blood Culture following Prolonged Exercise.

    Science.gov (United States)

    Svendsen, Ida S; Killer, Sophie C; Gleeson, Michael

    2014-01-01

    Elevated antigen-stimulated anti-inflammatory cytokine production appears to be a risk factor for upper respiratory tract illness in athletes. The purpose of this study was to determine the effects of prolonged exercise and hydration on antigen-stimulated cytokine production. Twelve healthy males cycled for 120 min at 60% [Formula: see text] on two occasions, either euhydrated or moderately hypohydrated (induced by fluid restriction for 24 h). Blood samples were collected before and after exercise and following 2 h recovery for determination of cell counts, plasma cortisol, and in vitro antigen-stimulated cytokine production by whole blood culture. Fluid restriction resulted in mean body mass loss of 1.3% and 3.9% before and after exercise, respectively. Exercise elicited a significant leukocytosis and elevated plasma cortisol, with no differences between trials. IL-6 production was significantly reduced 2 h postexercise (P hydration status was observed for the measured variables. Prolonged exercise appears to result in augmented anti-inflammatory cytokine release in response to antigen challenge, possibly coupled with acute suppression of proinflammatory cytokine production, corresponding with studies using mitogen or endotoxin as stimulant. Moderate hypohydration does not appear to influence these changes. PMID:24967270

  17. An Onion Byproduct Affects Plasma Lipids in Healthy Rats

    DEFF Research Database (Denmark)

    Roldan-Marin, E.; Jensen, R. I.; Krath, Britta;

    2010-01-01

    that the controls could be completely separated from OBP, OE, and OR groups in the scores plot and also that OE and OR groups were separated. Plasma lipids and bile acid excretion were the discriminating loading factors for separating OE and OR but also contributed to the separation of onion......Onion may contribute to the health effects associated with high fruit and vegetable consumption. A considerable amount of onion production ends up as waste that might find use in foods. Onion byproduct has not yet been explored for potential health benefits. The aim of this study is to elucidate...... the safety and potential role of onion byproducts in affecting risk markers of cardiovascular disease (CVD). For that purpose, the effects of an onion byproduct, Allium cepa L. cepa 'Recas' (OBP), and its two derived fractions, an ethanolic extract (OE) and a residue (OR), on the distribution of...

  18. Biocompatibility of hemodialysis membranes: interrelations between plasma complement and cytokine levels.

    Science.gov (United States)

    Varela, M P; Kimmel, P L; Phillips, T M; Mishkin, G J; Lew, S Q; Bosch, J P

    2001-01-01

    Hemodialysis (HD) membrane biocompatibility is defined as absence of complement activation. We have recently shown that circulating levels of interleukin (IL) 1 and IL-2 predict death and survival, respectively, of HD patients. Studies have assessed IL-1 in treatments with biocompatible and less biocompatible dialysis membranes, but no study has correlated circulating levels of all these immunoreactants. We assessed these immunoreactants, and temperature as an outcome, during HD in patients treated with different membranes. Twelve stable patients, receiving thrice-weekly chronic bicarbonate HD, were randomly dialyzed with three different types of membranes, composed of: Cuprophan, cuprammonium rayon modified cellulose, and Hemophan. Blood was drawn from the arterial line port before (Pre) and 15, 30, and 60 min during and after (Post) HD. Patients' temperatures were measured before and after each treatment. The plasma concentrations of IL-1 and IL-2 and factors C3a and C5a were assessed by ELISA. There were no differences between baseline levels of any of the immunoreactants in patients treated with different dialyzers. C3a, C5a, and IL-1 levels increased significantly during HD treatments with all three different membranes. C3a, C5a, and IL-1 levels during Cuprophan and Hemophan treatments were significantly higher than the levels during modified cellulose treatment at 30 and 60 min and Post (p < 0.01). For all the immunoreactants, however, the Post levels were higher than the Pre levels. In contrast to IL-1, there were no differences in mean IL-2 levels during treatments when different membranes were compared. There were few correlations of plasma C3a and C5a levels with plasma IL-1 levels, but there was only one treatment time in one dialyzer group during which IL-2 and any of the other factors were correlated. Pre and Post temperature values and percent change in temperature were not correlated with any of the immunoreactants measured. These data show that C3a

  19. Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors.

    Directory of Open Access Journals (Sweden)

    Mirjam E Belderbos

    Full Text Available Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP or soluble CD14 (sCD14. The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection.

  20. THE EFFECT OF TAPERING PERIOD ON PLASMA PRO-INFLAMMATORY CYTOKINE LEVELS AND PERFORMANCE IN ELITE MALE CYCLISTS

    Directory of Open Access Journals (Sweden)

    Peter M. Tiidus

    2009-12-01

    Full Text Available The aim of this study was to investigate the effect of two different tapering period lengths on the concentration of plasma interleukin- 6 (IL-6, interleukin (IL-1β and tumor necrosis factor-? (TNF-α and performance in elite male cyclists. To this end, after completing 8 weeks progressive endurance exercise, twenty four high-level endurance cyclists were randomly assigned to one of two groups: a control group of cyclists (n = 12 continued performing progressive weekly training volume for 3 weeks while a taper group of cyclists (n = 12 proceeded with a 50% reduction in weekly training volume relative to the control group. A simulated 40 min time trial (40TT performance ride was used as the criterion index of performance before and after the tapering period to evaluate the physiological and performance effects of each protocol. Blood samples were collected immediately post-40TT from all participants at the beginning of week 1, and the end of weeks 4, 8, 9 and 11. IL-1β, IL-6 and TNFα were assayed using a standard commercial ELISA kits (Quantikine; R & D Systems, Minneapolis, MN. The mean time to complete the 40TT in the taper group decreased significantly (p < 0.01 after both 1 and 3 weeks with reduced training volume relative to the control group. There were significant reductions in (p < 0.001 IL-1β, IL-6 and TNFα concentrations in the taper group relative to the control group at the end of the 3 week tapering period, but not at the end of the 1 week tapering period. These results demonstrate that both a 1 and a 3 week taper period will result in improved physical performance in trained cyclists but only a 3 week taper period will result in attenuation of post-exercise pro- inflammatory cytokines when compared to those continuing a more intense training regimen

  1. How various plasma sources may affect seed germination and growth

    Czech Academy of Sciences Publication Activity Database

    Šerá, Božena; Gajdová, Iveta; Čermák, M.; Gavril, B.; Hnatiuc, E.; Kováčik, D.; Kříha, V.; Sláma, J.; Šerý, M.; Špatenka, P.

    Brasov : Universitatea Transilvania din Brasov, 2012 - (Clotea, L.; Cernat, M.). s. 250-250 ISBN 978-1-4673-1650-7. [International Conference on Optimization of Electrical and Electronic Equipment /13./ OPTIM 2012. 24.05.-26.05.2012, Brasov] Institutional research plan: CEZ:AV0Z60870520 Keywords : seed germination * bio- plasma * nonthermal plasma * biotechnology Subject RIV: EI - Biotechnology ; Bionics

  2. Cyclosporine A affects the in vitro expression of T cell activation-related molecules and cytokines in dogs.

    Science.gov (United States)

    Fellman, C L; Stokes, J V; Archer, T M; Pinchuk, L M; Lunsford, K V; Mackin, A J

    2011-04-15

    Cyclosporine is a powerful immunosuppressive drug that is being used with increasing frequency to treat a wide range of immune-mediated diseases in the dog. To date, ideal dosing protocols that will achieve immunosuppression with cyclosporine in dogs remain unclear, and standard methods that can measure effectiveness of immunosuppression have not been established. The aim of our study was to evaluate the effects of in vitro cyclosporine exposure on a panel of molecules expressed by activated T cells to ascertain their potential as biomarkers of immunosuppression in dogs. Blood was drawn from six healthy dogs, and peripheral blood mononuclear cells (PBMC) were isolated and activated. Half of the cells were incubated with 200 ng/mL cyclosporine prior to activation, and the other half were not exposed to cyclosporine. Samples were analyzed using flow cytometry, and the expression of intracellular cytokines IL-2, IL-4, and IFN-γ was evaluated after 6, 12, and 24h of drug exposure. Each cytokine exhibited a time-dependent suppression profile, and all but two samples activated in the presence of cyclosporine showed lower cytokine expression than untreated controls. We also evaluated the expression of the surface T cell activation molecules CD25 and CD95 by flow cytometry after 36 h of drug exposure. Expression of these surface molecules decreased significantly when activated in the presence of cyclosporine. Our results suggest that suppressed expression of the markers related to T cell activation could potentially be utilized as an indicator of the efficacy of cyclosporine therapy in dogs. PMID:21227512

  3. MicroRNA-155 may affect allograft survival by regulating the expression of suppressor of cytokine signaling 1.

    Science.gov (United States)

    Zhang, Maomao; Zhang, Qi; Liu, Fang; Yin, Li; Yu, Bo; Wu, Jian

    2011-10-01

    Immune rejection of organ transplants has life-threatening implications. It is believed that allograft rejection is initiated by the activation of lymphocytes following recognition of donor antigens, leading to generation of effector T lymphocytes, alloantibody production, and graft infiltration by alloreactive cells. There is solid evidence that miRNAs are integral for maintaining immune homeostasis and self-tolerance. A deeper understanding of the regulation of the immune response by miRNAs could define new mechanisms for manipulating graft immunity and preventing rejection. The miRNA miR-155 is of particular interest due to its known roles in regulating the expression of genes relevant to allograft rejection and the induction of immune tolerance. Indeed, miR-155 has been shown to dramatically impact both innate and adaptive immune processes, including inflammation, antigen presentation, T-cell differentiation, cytokine production, and T regulatory cell (Treg) functions. The suppressor of cytokine signaling 1 (SOCS1) is a critical regulator of immune cell function and an evolutionarily conserved target of miR-155 in breast cancer cells. We propose that suppression of miR-155 could enhance SOCS1 expression in immune cells and suppress allograft rejection. Further studies on the specific role of miR-155 in allograft rejection may lead to the identification of new targets for therapeutic intervention. PMID:21802214

  4. Feeding a high dosage of zinc oxide affects suppressor of cytokine gene expression in Salmonella Typhimurium infected piglets.

    Science.gov (United States)

    Schulte, Jasper N; Brockmann, Gudrun A; Kreuzer-Redmer, Susanne

    2016-10-01

    Suppressor of cytokine signaling (SOCS) proteins play an important role in the regulation of the immune response by inhibiting cytokines. Here we investigated the effects of zinc oxide fed at three different dosages (LZN=57ppm, MZN=167ppm, HZN=2425ppm) to weaned piglets that were or were not orally infected with Salmonella enterica serovar Typhimurium DT 104. We detected higher expression of SOCS3 six days after weaning for all analyzed piglets, regardless of the infection or the zinc feeding, suggesting a stress induced immune response. Whereas, SOCS1 showed only higher transcript amounts in S. Typhimurium infected piglets, especially the LZN group. This might indicate an infection regulating effect of zinc oxide in the infection model. After 42days of infection, the expression of SOCS2, SOCS4, and SOCS7 was increased only in animals fed the highest concentrations of zinc oxide, while non-infected piglets at the age of 56days showed no regulation for these genes. The up-regulation of SOCS genes in the mesenteric lymph nodes of piglets fed a diet with a very high concentration of zinc over 6 weeks suggests that such treatments may impair the immune response. PMID:27496737

  5. How various plasma sources may affect seed gemination and growth

    Czech Academy of Sciences Publication Activity Database

    Šerá, Božena; Gajdová, Iveta; Čermák, M.; Gavril, B.; Hnatiuc, E.; Kováčik, D.; Kříha, V.; Sláma, J.; Šerý, M.; Špatenka, P.

    Brasov: Universitatea Transilvania din Brasov, 2012 - (Clotea, L.; Cernat, M.), s. 1365-1370 ISBN 978-1-4673-1650-7. [Optimization of Electrical and Electronic Equipment (OPTIM), 2012 13th International Conference. Brasov (RO), 24.05.2012-26.05.2012] Institutional support: RVO:67179843 Keywords : non thermal plasma * atmospheric pressure * biotechnology * systems biology * seed germination * early growth Subject RIV: EI - Biotechnology ; Bionics

  6. A rapid, accurate and robust particle-based assay for the simultaneous screening of plasma samples for the presence of five different anti-cytokine autoantibodies

    DEFF Research Database (Denmark)

    Guldager, Daniel Kring Rasmussen; von Stemann, Jakob Hjorth; Larsen, Rune;

    2015-01-01

    PURPOSE: To establish and validate a rapid, cost-effective and accurate screening assay for the simultaneous testing of human naturally occurring anti-cytokine autoantibodies (c-aAb) targeting interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-10 (IL-10), granulocyte-macrophage colony...... METHODS: The microsphere-based Luminex platform was used. Recombinant forms of human IL-1α, IL-6, IL-10, GM-CSF, and IFNα were gently coupled to MAG-PLEX beads. Plasma IgG binding was measured with phycoerythrin (PE)-labeled secondary antibodies. Previously confirmed c-aAb positive and negative donor...

  7. Plasma PGE-2 levels and altered cytokine profiles in adherent peripheral blood mononuclear cells in non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Hirschowitz Edward A

    2002-11-01

    Full Text Available Abstract Introduction PGE-2 is constitutively produced by many non-small cell lung cancers (NSCLC and its immunosuppressive effects have been linked to altered immune responses in lung cancer. We asked whether elevated levels of plasma PGE-2 correlated with monocyte IL10 production in the NSCLC environment. Looking for correlation in NSCLC patient blood we assayed plasma from NSCLC patients for PGE2 and IL10; we further evaluated production of IL10 by adherent mononuclear cells from a subset of these patients looking for an altered cytokine profile. Results Our initial in vitro experiments show that monocyte IL10 induction correlates with tumor cell PGE-2 production, confirming similar reports in the literature. Data show plasma PGE-2 levels in 38 NSCLC patients are elevated compared to normal controls. Plasma IL10 levels were not significantly elevated; however, adherent monocytes derived from NSCLC patient blood did produce significantly more IL10 in 24 hr primary culture than those from normal controls (p Conclusions Elevated plasma PGE-2 and monocyte IL10 production are associated with NSCLC. The biological significance to elevated PGE-2 levels in NSCLC are unclear. Further investigation of each as a nonspecific marker for NSCLC tumor is warranted.

  8. Two Consecutive Days of Crossfit Training Affects Pro and Anti-inflammatory Cytokines and Osteoprotegerin without Impairments in Muscle Power.

    Science.gov (United States)

    Tibana, Ramires A; de Almeida, Leonardo M; Frade de Sousa, Nuno M; Nascimento, Dahan da Cunha; Neto, Ivo V de Sousa; de Almeida, Jeeser A; de Souza, Vinicius C; Lopes, Maria de Fátima T P L; Nobrega, Otávio de Tolêdo; Vieira, Denis C L; Navalta, James W; Prestes, Jonato

    2016-01-01

    The aim of this study was to investigate the effects of two consecutive Crossfit® training sessions (24 h apart) designed to enhance work-capacity that involved both cardiovascular and muscular exercises on cytokines, muscle power, blood lactate and glucose. Nine male members of the CrossFit® community (age 26.7 ± 6.6 years; body mass 78.8 ± 13.2 kg; body fat 13.5 ± 6.2%; training experience 2.5 ± 1.2 years) completed two experimental protocols (24 h apart): (1) strength and power exercises, (2) gymnastic movements, and (3) metabolic conditioning as follows: 10 min of as many rounds as possible (AMRAP) of 30 double-unders and 15 power snatches (34 kg). The same sequence as repeated on session 2 with the following metabolic conditioning: 12 min AMRAP of: row 250 m and 25 target burpees. Serum interleukin-6 (IL-6), IL-10, and osteoprotegerin were measured before, immediately post and 24 h after workout of the day (WOD) 1, immediately post, 24 and 48 h after WOD 2. Peak and mean power were obtained for each repetition (back squat with 50% of 1 repetition maximum) using a linear position transducer measured before, immediately post and 24 h after WOD 1, immediately post and 24 h after WOD 2. Blood lactate and glucose were measured pre and immediately post WOD 1 and 2. Although both sessions of exercise elicited an significant increase in blood lactate (1.20 ± 0.41 to 11.84 ± 1.34 vs. 0.94 ± 0.34 to 9.05 ± 2.56 mmol/l) and glucose concentration (81.59 ± 10.27 to 114.99 ± 12.52 vs. 69.47 ± 6.97 to 89.95 ± 19.26 mg/dL), WOD 1 induced a significantly greater increase than WOD 2 (p ≤ 0.05). The training sessions elicited significant changes (p ≤ 0.05) in IL-6, IL-10 and osteoprotegerin concentration over time. IL-6 displayed an increase immediately after training WOD 1 [197 ± 109%] (p = 0.009) and 2 [99 ± 58%] (p = 0.045). IL-10 displayed an increase immediately after only WOD 1 [44 ± 52%] (p = 0.046), and decreased 24 and 48 h following WOD 2 (~40%; p

  9. Two Consecutive Days of Crossfit Training Affects Pro and Anti-inflammatory Cytokines and Osteoprotegerin without Impairments in Muscle Power

    Science.gov (United States)

    Tibana, Ramires A.; de Almeida, Leonardo M.; Frade de Sousa, Nuno M.; Nascimento, Dahan da Cunha; Neto, Ivo V. de Sousa; de Almeida, Jeeser A.; de Souza, Vinicius C.; Lopes, Maria de Fátima T. P. L.; Nobrega, Otávio de Tolêdo; Vieira, Denis C. L.; Navalta, James W.; Prestes, Jonato

    2016-01-01

    The aim of this study was to investigate the effects of two consecutive Crossfit® training sessions (24 h apart) designed to enhance work-capacity that involved both cardiovascular and muscular exercises on cytokines, muscle power, blood lactate and glucose. Nine male members of the CrossFit® community (age 26.7 ± 6.6 years; body mass 78.8 ± 13.2 kg; body fat 13.5 ± 6.2%; training experience 2.5 ± 1.2 years) completed two experimental protocols (24 h apart): (1) strength and power exercises, (2) gymnastic movements, and (3) metabolic conditioning as follows: 10 min of as many rounds as possible (AMRAP) of 30 double-unders and 15 power snatches (34 kg). The same sequence as repeated on session 2 with the following metabolic conditioning: 12 min AMRAP of: row 250 m and 25 target burpees. Serum interleukin-6 (IL-6), IL-10, and osteoprotegerin were measured before, immediately post and 24 h after workout of the day (WOD) 1, immediately post, 24 and 48 h after WOD 2. Peak and mean power were obtained for each repetition (back squat with 50% of 1 repetition maximum) using a linear position transducer measured before, immediately post and 24 h after WOD 1, immediately post and 24 h after WOD 2. Blood lactate and glucose were measured pre and immediately post WOD 1 and 2. Although both sessions of exercise elicited an significant increase in blood lactate (1.20 ± 0.41 to 11.84 ± 1.34 vs. 0.94 ± 0.34 to 9.05 ± 2.56 mmol/l) and glucose concentration (81.59 ± 10.27 to 114.99 ± 12.52 vs. 69.47 ± 6.97 to 89.95 ± 19.26 mg/dL), WOD 1 induced a significantly greater increase than WOD 2 (p ≤ 0.05). The training sessions elicited significant changes (p ≤ 0.05) in IL-6, IL-10 and osteoprotegerin concentration over time. IL-6 displayed an increase immediately after training WOD 1 [197 ± 109%] (p = 0.009) and 2 [99 ± 58%] (p = 0.045). IL-10 displayed an increase immediately after only WOD 1 [44 ± 52%] (p = 0.046), and decreased 24 and 48 h following WOD 2 (~40%; p

  10. Changes in Dietary Fat Content Rapidly Alters the Mouse Plasma Coagulation Profile without Affecting Relative Transcript Levels of Coagulation Factors

    Science.gov (United States)

    van Diepen, Janna A.; Verhoef, Daniël; Voshol, Peter J.; Reitsma, Pieter H.; van Vlijmen, Bart J. M.

    2015-01-01

    Background Obesity is associated with a hypercoagulable state and increased risk for thrombotic cardiovascular events. Objective Establish the onset and reversibility of the hypercoagulable state during the development and regression of nutritionally-induced obesity in mice, and its relation to transcriptional changes and clearance rates of coagulation factors as well as its relation to changes in metabolic and inflammatory parameters. Methods Male C57BL/6J mice were fed a low fat (10% kcal as fat; LFD) or high fat diet (45% kcal as fat; HFD) for 2, 4, 8 or 16 weeks. To study the effects of weight loss, mice were fed the HFD for 16 weeks and switched to the LFD for 1, 2 or 4 weeks. For each time point analyses of plasma and hepatic mRNA levels of coagulation factors were performed after overnight fasting, as well as measurements of circulating metabolic and inflammatory parameters. Furthermore, in vivo clearance rates of human factor (F) VII, FVIII and FIX proteins were determined after 2 weeks of HFD-feeding. Results HFD feeding gradually increased the body and liver weight, which was accompanied by a significant increase in plasma glucose levels from 8 weeks onwards, while insulin levels were affected after 16 weeks. Besides a transient rise in cytokine levels at 2 weeks after starting the HFD, no significant effect on inflammation markers was present. Increased plasma levels of fibrinogen, FII, FVII, FVIII, FIX, FXI and FXII were observed in mice on a HFD for 2 weeks, which in general persisted throughout the 16 weeks of HFD-feeding. Interestingly, with the exception of FXI the effects on plasma coagulation levels were not paralleled by changes in relative transcript levels in the liver, nor by decreased clearance rates. Switching from HFD to LFD reversed the HFD-induced procoagulant shift in plasma, again not coinciding with transcriptional modulation. Conclusions Changes in dietary fat content rapidly alter the mouse plasma coagulation profile, thereby

  11. Plasma Interleukin-37 Is Elevated in Patients with Rheumatoid Arthritis: Its Correlation with Disease Activity and Th1/Th2/Th17-Related Cytokines

    Directory of Open Access Journals (Sweden)

    Ting Xia

    2015-01-01

    Full Text Available Interleukin- (IL- 37 is a novel anti-inflammatory cytokine that suppresses immune response and inflammation. This study was performed to determine whether IL-37 was elevated in patients with rheumatoid arthritis (RA and investigate the correlation between IL-37 level and disease activity and the concentration of Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity, including the 28-joint disease activity score (DAS28 and C-reactive protein (CRP, were collected in 34 RA patients and 34 age- and sex-matched healthy controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, and MIP-1β were analyzed using the Bio-Plex suspension array system. It was found that IL-37 levels were elevated markedly in RA patients and almost undetectable in healthy controls. In addition, IL-37 levels in patients with active RA were significantly enhanced as compared with those in patients of remission. More importantly, IL-37 showed a significant correlation with disease activity (DAS28 and IL-4, IL-7, IL-10, IL-12, and IL-13 concentrations in RA patients. These findings suggest that IL-37 plays an important role in the pathogenesis of RA and may prove to be a potential biomarker of active RA.

  12. Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic patients with multiple myeloma and monoclonal gammopathies of undetermined significance

    International Nuclear Information System (INIS)

    Multiple myeloma (MM) is a common malignancy manifest by bone marrow infiltration with malignant plasma cells, the production of a paraprotein and lytic bone lesions. Monoclonal gammopathy of undetermined significance (MGUS) is assumed to be the precursor of clinically apparent myeloma, with one or more additional genetic events being required for progression to MM. Elderly patients presenting with osteoporosis and skeletal fractures are not infrequently found to have elevated serum paraprotein concentrations suggestive of either MM or MGUS. Differentiating between these two clinical disorders may prove challenging, despite bone marrow biopsy evidence of plasmacytosis. The underlying pathogenesis of bone loss in these conditions is complex and may be attributed to cytokine-induced osteoclastogenesis coupled with increased osteoclastic bone resorption. In the present study, various markers of bone turnover and plasma cytokines were measured in order to determine whether they may be of value in differentiating between these two disorders. It is concluded that the urinary deoxypyridinoline excretion rate is a sensitive marker of bone resorption and of underlying bone disease activity. It may also help to differentiate between MM and MGUS

  13. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

    2012-01-01

    BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...... to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder...

  14. The Liposuction-Induced Effects on Adiponectin and Selected Cytokines Are Not Affected by Exercise Training in Women

    OpenAIRE

    Marina Yazigi Solis; Guilherme Giannini Artioli; Eduardo Montag; Vitor de Salles Painelli; Fábio Lopes Saito; Fernanda Rodrigues Lima; Hamilton Roschel; Bruno Gualano; Antonio Herbert Lancha Junior; Fabiana Braga Benatti

    2014-01-01

    It has been suggested that the abrupt liposuction-induced decrease in adipose tissue could affect adipokine secretion pattern. We hypothesized that exercise training could positively impact adipokine metabolism following liposuction. The aim of this study was to investigate the effects of liposuction on inflammation-related adipokines in women who were either exercise-trained or remained sedentary after surgery. Thirty-six healthy normal-weight women underwent an abdominal liposuction and two...

  15. Circulating cytokines and chemokines associated with plasma leakage and hepatic dysfunction in Brazilian children with dengue fever.

    Science.gov (United States)

    Ferreira, Ralph Antonio Xavier; de Oliveira, Solange Artimos; Gandini, Mariana; Ferreira, Laura da Cunha; Correa, Gladys; Abiraude, Fernanda Mattos; Reid, Mariana Mancebo; Cruz, Oswaldo Gonçalves; Kubelka, Claire Fernandes

    2015-09-01

    Dengue fever is usually a benign acute viral infection transmitted by arthropods but may evolve to severe clinical manifestations such as coagulation and/or hemodynamic disorders, caused mainly by an increase of vascular permeability. Deregulated circulating immunological factors have been associated with severity. In Brazil severe cases appeared in children only recently and we evaluated the profile of cytokine/chemokine kinetics in 134 hospitalized young patients during the epidemic in Rio de Janeiro in 2008. Inflammatory cytokines TNF and IFNγ were found elevated during the acute phase in children as well as the anti-inflammatory IL10 and chemokines MIF and CXCL10/IP10, all last three persisting longer during the recovery phase. Severe disease fitting the dengue hemorrhagic fever pattern (WHO, 1997) was associated with higher IL10 and CXCL10/IP10 circulating levels (peak levels at seven days with Phistory of prior infection (93%). This is the first study demonstrating cytokine and chemokine association with severity during dengue fever in Brazilian children. IL10 and CXCL10/IP10 play a role in the disease severity associated with induction of vascular leakage and a novel association with changes in liver dysfunction. PMID:25944351

  16. Clove (Syzygium aromaticum) ingredients affect lymphocyte subtypes expansion and cytokine profile responses: An in vitro evaluation

    OpenAIRE

    Shaghayegh Pishkhan Dibazar; Shirin Fateh; Saeed Daneshmandi

    2014-01-01

    Clove (Syzygium aromaticum) has been used in folk medicine in many disorders. The present work aimed to investigate effects of clove essential oil as eugenol and water soluble ingredients on mouse splenocytes. Clove extracts were harvested and in different concentrations (0.001–1000 μg/mL) were affected to splenocytes and also phytohemagglutinin (PHA = 5 μg/mL) and lipopolysaccharide (LPS = 10 μg/mL) activated splenocytes; then splenocytes proliferation assayed using the MTT ([3-(4, 5-dimethy...

  17. Role of different cytokines and seizure susceptibility: a new dimension towards epilepsy research.

    Science.gov (United States)

    Rao, R S; Prakash, A; Medhi, B

    2009-08-01

    Epilepsy is a common health problem. Although variety of factors influence the incidence and prevalence of seizures, cytokines are considered to play an important role in seizures. Cytokines are also known to be involved in other neurodegenerative disorders. Proinflammatory cytokines like IL-1, IL-6, TNF-alpha and growth factor vascular endothelial growth factor (VEGF) as well as anti-inflammatory cytokine IL-10 and related molecules have been described in CNS and plasma of experimental models of seizures and clinical cases of epilepsy. There are reports suggesting more predispositions to seizures during inflammatory conditions like colitis, pneumonia and rheumatoid arthritis. These inflammatory cytokines and growth factors are also known to have dual roles in affecting seizure susceptibility. It remains to be seen if cytokine modulators can be therapeutically exploited for patients with inflammatory disorder and suffering from epilepsy. PMID:19775068

  18. Sunlight–derived vitamin D affects interleukin-4 level, T helper 2 serum cytokines, in patients with Graves’ disease: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Dyah Purnamasari

    2015-12-01

    Full Text Available Background: Graves’ disease (GD is the most common autoimmune disease leading to hyperthyroidism. The role of Th1/Th2 pathways balance in GD is still controversial. Vitamin D is reported to have an effect on those pathways. This study aims to examine the effect of sunlight exposure on vitamin D 25(OH level and Th1 and Th2 pathway-derived cytokines in GD patients. Methods: A prospective cohort study was conducted on 32 GD patients to compare the effect of sunlight exposure on vitamin D level and cytokines of Th1 and Th2 pathways between exposed and unexposed groups. Exposed group received sunlight exposure three times a week for 30 minutes each between 9–11 a.m for 1 month. Thyroid stimulating hormone (TSH, free thyroxin (fT4, vitamin D 25(OH, interferon-γ (IFN-γ and interleukin-4 (IL-4 serum levels, were investigated before and after one month of sunlight exposure. Paired t-test or Mann Whitney test were used to analyze the difference between exposed and unexposed GD groups before and after sun exposure.Results: One month of sunlight exposure increased vitamin D 25(OH level by 27.90% among exposed GD group (15.34 ng/mL to 19.62 ng/mL, p<0.001. Meanwhile, unexposed GD group’s vitamin D 25(OH level decreased from 20.48 ng/mL to 18.86 ng/mL (p<0.001. Increased vitamin D 25(OH level in exposed group was not accompanied by the increase of IL-4 level after sunlight exposure.Conclusion: Sunlight exposure increases vitamin D 25(OH serum level and may affect the level of IL-4, Th2 pathway-derived cytokine, in patients with GD. However, the role of sunlight-derived vitamin D on IFN-γ in GD patients can not be concluded in this study.

  19. The Liposuction-Induced Effects on Adiponectin and Selected Cytokines Are Not Affected by Exercise Training in Women

    Directory of Open Access Journals (Sweden)

    Marina Yazigi Solis

    2014-01-01

    Full Text Available It has been suggested that the abrupt liposuction-induced decrease in adipose tissue could affect adipokine secretion pattern. We hypothesized that exercise training could positively impact adipokine metabolism following liposuction. The aim of this study was to investigate the effects of liposuction on inflammation-related adipokines in women who were either exercise-trained or remained sedentary after surgery. Thirty-six healthy normal-weight women underwent an abdominal liposuction and two months after surgery were randomly allocated into two groups: trained (TR, n=18, four-month exercise program and nontrained (NT, n=18. Inflammation-related adipokine serum levels (TNF-α, IL-6, IL-10, and adiponectin and abdominal and thigh subcutaneous adipose tissue (scAT mRNA levels were assessed before (PRE and six months after surgery (POST6. TNF-α, IL-6, and IL-10 serum levels were unchanged in both groups. In contrast, TNF-α, IL-6, and IL-10 mRNA levels in scAT were increased, whereas adiponectin scAT mRNA and serum levels were decreased at POST6 (P<0.05, main effect for time. No changes were observed in mRNA levels of MCP-1, CD14, and CD68 in any of the groups. In conclusion, liposuction downregulates adiponectin scAT gene expression and serum levels and upregulates scAT gene expression of inflammation-related genes six months after surgery in normal-weight women, irrespective of exercise training.

  20. Detection and quantitation of twenty-seven cytokines, chemokines and growth factors pre- and post-high abundance protein depletion in human plasma

    Directory of Open Access Journals (Sweden)

    Seong-Beom Ahn

    2014-06-01

    Full Text Available Cytokines, chemokines and growth factors (CCGFs in human plasma are analyzed for identification of biomarkers. However concentrations of CCGFs are very low; it is difficult to identify and quantify low abundance proteins in the presence of the high abundance proteins (HAPs unless HAPs are removed prior to analysis. However, there is a concern that the low abundance proteins such as CCGFs may also be removed during the HAP depletion process. In this study, we have examined whether or not depletion of the HAPs enhances detection of the CCGFs by immuno-assays. Top 14 HAPs were depleted from 10 healthy volunteers’ plasma using MARS-14 immuno-depletion column and a total of 27 CCGFs were analyzed by bead-based multiplexed immuno-assay. All 27 CCGFs were detected in neat plasma (NP, 25 were detected in flow through fraction (FT and 21 were detected in bound protein (BP fraction. Concentrations of 22 CCGFs were significantly higher in NP compared to FT and BP. Only one CCGF had higher concentration in FT compared to NP. The remaining 2 CCGFs were not different between NP and FT. It was counter-productive for the detection of 24 CCGFs after HAP removal, primarily due to post-depletion protein precipitation and/or re-suspension of pellets.

  1. Clinical significance of measurement of plasma relevant cytokines (GM-CSF, IL-2, TPO, EPO) levels in patients with aplastic anemia

    International Nuclear Information System (INIS)

    Objective: To investigate the role of relevant cytokines in the development and pathogenesis of aplastic anemia. Methods: Plasma GM-CSF, IL-2, TPO (with RIA) and EPO (with CLIA) contents were measured in 100 patients (acute 43, chronic 57) with aplastic anemia and 50 controls. Complete blood count was also performed in all these subjects. Results: The peripheral RBC, WBC, platelet counts and GM-CSF contents were significantly lower in the patients with aplastic anemia than those in the controls (P<0.05), while the IL-2, EPO and TPO contents were significantly higher in the patients (P<0.05). GM-CSF contents were positively correlated with the WBC numbers. EPO contents were negatively correlated with the RBC counts and TPO contents were correlated (negatively) with the platelet counts. Conclusion: There was correlationship between each blood elements (WBC, RBC, platelet) and its corresponding cytokine (GS-CSF, EPO, TPO respectively). IL-2 contents were not correlated with WBC counts. (authors)

  2. Plasma cytokine levels in young and elderly twins: genes versus environment and relation to in vivo insulin action

    DEFF Research Database (Denmark)

    Grunnet, L; Poulsen, P; Klarlund Pedersen, B; Mandrup-Poulsen, Thomas; Vaag, A

    2006-01-01

    We studied the impact of genetic versus pre- and postnatal environmental factors on the plasma levels of IL6, TNF and the soluble TNF receptor superfamily, member 1A (TNFRSF1A, previously known as TNF receptor type1 [TNFR1])....

  3. Factors which affect operation of a plasma focus in various gases

    International Nuclear Information System (INIS)

    It is shown that the axial transit time ta and the ratio of specific heats are the main factors which affect the operation of a plasma focus in various gases. An energy balance theory is used to explore this dependence. The results are consistent with previous calculations and with experiments. (author)

  4. Studies on Factors Affecting Plasma PIVKA-II Levels in Hepatocellular Carcinoma

    OpenAIRE

    Soga, Kenji; Arai, Futoshi; Tsuruya, Takashi; Aikawa, Keiko; Toshima, Muneatsu; Shibasaki, Koichi; Aoyagi, Yutaka

    1993-01-01

    In order to diagnose hepatocellular carcinoma (HCC), plasma levels of protein induced by vitamin K absence or antagonist-II (PIVKA-II) were determined by an enzyme-linked immunosorbent assay (ELISA). Positive reaction was noted in 34 (68%) of 50 patients with HCC, with PIVKA-II serving as an useful tumor marker in the estimation of HCC staging. On the other hand, the administration of vitamin K and the presence of jaundice were found to be important factors that affect plasma PIVKA-II levels....

  5. Short Hypoxia Does not Affect Plasma Leptin in Healthy Men under Euglycemic Clamp Conditions

    Directory of Open Access Journals (Sweden)

    Andre Schmoller

    2009-01-01

    Full Text Available Leptin is involved in the endocrine control of energy expenditure and body weight regulation. Previous studies emphasize a relationship between hypoxic states and leptin concentrations. The aim of this study was to investigate the effects of acute hypoxia on leptin concentrations in healthy subjects. We examined 14 healthy men. Hypoxic conditions were induced by decreasing oxygen saturation to 75% for 30 minutes. Plasma leptin concentrations were determined at baseline, after 3 hours of euglycemic clamping, during hypoxia, and repeatedly the following 2.5 hours thereafter. Our results show an increase of plasma leptin concentrations in the course of 6 hours of hyperinsulinemic-euglycemic clamping which may reflect diurnal rhythmicity. Notwithstanding, there was no difference between levels of leptin in the hypoxic and the normoxic condition (=.2. Since we did not find any significant changes in leptin responses upon hypoxia, plasma leptin levels do not seem to be affected by short hypoxic episodes of moderate degree.

  6. Therapeutic control of plasma concentrations and long-term effect of nortriptyline in recurrent affective disorders.

    Science.gov (United States)

    Kragh-Sørensen; Hansen, C E; Baastrup, P C; Hvidberg, E F

    1976-07-01

    Based on the evidence that therapeutic plasma concentration range in fact exists for the tricyclic antidepressant drug, Nortriptyline (range 50-150 ng/ml), three different investigations were under taken in order to clarify some clinical pharmacological problems during long-term treatment with this drug. The possible prophlactic effect of the drug in recurrent affective disorders was specially examined in a group of patients with a high risk of episodes in their unipolar manic-depressive disease. The results highly demonstrate the value of monitoring plasma levels in achieving therapeutic control. Depressive relapses during treatment, for months and years, were only related to therapeutic insufficient plasma levels of the drug. PMID:981330

  7. Synergistic and additive actions of a psychosocial stressor and endotoxin challenge: Circulating and brain cytokines, plasma corticosterone and behavioral changes in mice.

    Science.gov (United States)

    Gibb, Julie; Hayley, Shawn; Gandhi, Reno; Poulter, Michael O; Anisman, Hymie

    2008-05-01

    Activation of the inflammatory immune response may provoke neuroendocrine and central neurochemical effects that are reminiscent of those elicited by traditional stressors, and when administered concurrently may have synergistic effects. The present investigation assessed whether a psychosocial stressor, comprising social disruption, would augment the effects of lipopolysaccharide in mice. It was indeed observed that the social disruption engendered by a period of 2-4 weeks of social isolation (but not 1-7 days of this treatment) followed by regrouping, enhanced the effects of lipopolysaccharide (LPS: 10mug) in the provocation of sickness behavior, as well as plasma corticosterone, IL-6, TNF-alpha and IL-10 levels. Similar effects were not apparent with respect to IL-1beta, IL-4, or IFN-gamma. Synergy between LPS and other stressors (restraint, tail pinch, and loud noise) was not apparent with respect to sickness or plasma corticosterone, provisionally suggesting that social stressors, such as regrouping, may be more powerful or may engage unique neural or neuroendocrine circuits that favour synergistic outcomes. Within the CNS, the LPS and the regrouping stressor synergistically enhanced NE utilization within the prefrontal cortex, and additively influenced hippocampal NE utilization. In contrast to the effects on circulating cytokines, the LPS-induced elevation of IL-1beta, IL-6 and TNF-alpha mRNA expression in the hippocampus, PFC and nucleus tractus solitarius was diminished in animals that had experienced the regrouping stressor. In view of the combined actions of LPS challenge and a social stressor, these data are interpreted as suggesting that models of depression based on immune activation ought to consider the stressor backdrop upon which immune challenges are imposed. PMID:18191534

  8. Longitudinal instabilities affecting the moving critical layer laser-plasma ion accelerators

    CERN Document Server

    Sahai, Aakash Ajit

    2014-01-01

    In this work we analyze the longitudinal instabilities of propagating acceleration structures that are driven by a relativistically intense laser at the moving plasma critical layer [1]. These instabilities affect the energy-spectra of the accelerated ion-beams in propagating critical layer acceleration schemes [2][3]. Specifically, using analytical theory and PIC simulations we look into three fundamental physical processes and their interplay that are crucial to the understanding of energy spectral control by making the laser-plasma ion accelerators stable. The interacting processes are (i) Doppler-shifted ponderomotive bunching [1][4] (ii) potential quenching by beam-loading [2] and (iii) two-stream instabilities. These phenomenon have been observed in simulations analyzing these acceleration processes [5][6][7]. From the preliminary models and results we present in this work, we can infer measures by which these instabilities can be controlled [8] for improving the energy-spread of the beams.

  9. Zinc and copper levels in the plasma of Nubian goat as affected by the physiological status

    International Nuclear Information System (INIS)

    This study is undertaken directed to determine the blood concentration of micro (trace) minerals, particularly zinc (Zn) and copper (Cu), in dairy goats as affected by the different physiological status. Animals selected were the Nubian goats as an important dairy breed in sudan. The animals were divided into eight groups as follows: Young animals (4-6 month old), adult animals (9-12 month old), up to 50 days after first kidding, up to 50 days after second kidding, up to 50 days after third kidding, low yielder, high yielder. Each of the above groups consisted of 5 animals. The analysis was carried by using the spectrophotometer technique and the results revealed that, plasma Zn concentration decreased with increase of age while that of Cu increased with the increase of age. The plasma Zn level showed continuous increase through first pregnancy, after first kidding, after second kidding and after third kidding. It increased in the lactating animals. The plasma Cu concentration fluctuated throughout the groups with different physiological status, it showed the same levels in the pregnant group, up to 50 days after second kidding, and up to 50 days after third kidding groups, while it showed a marked decrease in the group of up to 50 days after first kidding. No significant differences were observed between the low lactating and the high lactating groups. (Author)

  10. Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and cell morphology of the temporal lobe

    Institute of Scientific and Technical Information of China (English)

    Guo-qing DI; Bing ZHOU; Zheng-guang; LI, Qi-li LIN

    2011-01-01

    In order to investigate the physiological effects of airport noise exposure on organisms,in this study,we exposed Sprague-Dawley rats in soundproof chambers to previously recorded aircraft-related noise for 65 d.For comparison,we also used unexposed control rats.Noise was arranged according to aircraft flight schedules and was adjusted to its weighted equivalent continuous perceived noise levels (LwEcPN) of 75 and 80 dB for the two experimental groups.We examined rat behaviors through an open field test and measured the concentrations of plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric detection (HPLC-FLD).We also examined the morphologies of neurons and synapses in the temporal lobe by transmission electron microscopy (TEM).Our results showed that rats exposed to airport noise of 80 dB had significantly lower line crossing number (P<0.05) and significantly longer center area duration (P<0.05) than control animals.After 29 d of airport noise exposure,the concentration of plasma NE of exposed rats was significantly higher than that of the control group (P<0.05).We also determined that the neuron and synapsis of the temporal lobe of rats showed signs of damage after aircraft noise of 80 dB exposure for 65 d.In conclusion,exposing rats to long-term aircraft noise affects their behaviors,plasma NE levels,and cell morphology of the temporal lobe.

  11. Some factors affecting the dynamics of a plasma-wall interaction simulator

    International Nuclear Information System (INIS)

    Isotope mixing and thermal desorption from samples exposed in a glow discharge apparatus were used to study the factors affecting hydrogen recycle and wall inventory. Conditions were chosen to be similar to those expected at the walls in today's experimental fusion devices. The size and nature of the hydrogen reservoir in the wall after plasma pulses was investigated by thermal desorption techniques. Large amounts of deuterium, i.e., 5 x 1015 D cm-2 remain in the sample 4 min after a single 200 ms plasma pulse. While this result may be explained by a model using bulk diffusion and traps, it is suggested that either a spectrum of desorption energies, or a concentration dependent recombination coefficient, may also be useful in describing the thermal desorption processes. Experiments with various pumping conditions show that readsorption of molecular hydrogen isotopes on the wall should be considered in modeling hydrogen recycle and isotope changeover processes. HD formation without plasmas confirms the role readsorption plays. (orig.)

  12. Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone.

    Science.gov (United States)

    Bosch, Oliver G; Eisenegger, Christoph; Gertsch, Jürg; von Rotz, Robin; Dornbierer, Dario; Gachet, M Salomé; Heinrichs, Markus; Wetter, Thomas C; Seifritz, Erich; Quednow, Boris B

    2015-12-01

    Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analogue-scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic-hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected. GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABAB-receptors and progesterone in mood and prosocial behavior. PMID:26209926

  13. Sunlight–derived vitamin D affects interleukin-4 level, T helper 2 serum cytokines, in patients with Graves’ disease: a prospective cohort study

    OpenAIRE

    Dyah Purnamasari; Pradana Soewondo; Samsuridjal Djauzi

    2015-01-01

    Background: Graves’ disease (GD) is the most common autoimmune disease leading to hyperthyroidism. The role of Th1/Th2 pathways balance in GD is still controversial. Vitamin D is reported to have an effect on those pathways. This study aims to examine the effect of sunlight exposure on vitamin D 25(OH) level and Th1 and Th2 pathway-derived cytokines in GD patients. Methods: A prospective cohort study was conducted on 32 GD patients to compare the effect of sunlight exposure on vitamin D level...

  14. Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and cell morphology of the temporal lobe.

    Science.gov (United States)

    Di, Guo-Qing; Zhou, Bing; Li, Zheng-Guang; Lin, Qi-Li

    2011-12-01

    In order to investigate the physiological effects of airport noise exposure on organisms, in this study, we exposed Sprague-Dawley rats in soundproof chambers to previously recorded aircraft-related noise for 65 d. For comparison, we also used unexposed control rats. Noise was arranged according to aircraft flight schedules and was adjusted to its weighted equivalent continuous perceived noise levels (L(WECPN)) of 75 and 80 dB for the two experimental groups. We examined rat behaviors through an open field test and measured the concentrations of plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric detection (HPLC-FLD). We also examined the morphologies of neurons and synapses in the temporal lobe by transmission electron microscopy (TEM). Our results showed that rats exposed to airport noise of 80 dB had significantly lower line crossing number (Paircraft noise of 80 dB exposure for 65 d. In conclusion, exposing rats to long-term aircraft noise affects their behaviors, plasma NE levels, and cell morphology of the temporal lobe. PMID:22135145

  15. Macrophage-stimulating protein differently affects human alveolar macrophages from smoker and non-smoker patients: evaluation of respiratory burst, cytokine release and NF-kappaB pathway.

    Science.gov (United States)

    Gunella, Gabriele; Bardelli, Claudio; Amoruso, Angela; Viano, Ilario; Balbo, Piero; Brunelleschi, Sandra

    2006-06-01

    Macrophage activation is a key feature of inflammatory reactions occurring during bacterial infections, immune responses and tissue injury. We previously demonstrated that human macrophages of different origin express the tyrosine kinase receptor recepteur d'origine nantaise, the human receptor for MSP (RON) and produce superoxide anion (O(2)(-)) when challenged with macrophage-stimulating protein (MSP), the endogenous ligand for RON. This study was aimed to evaluate the role of MSP in alveolar macrophages (AM) isolated from healthy volunteers and patients with interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis), either smokers or non-smokers, by evaluating the respiratory burst, cytokine release and nuclear factor-kappa B (NF-kappaB) activation. MSP effects were compared with those induced by known AM stimuli, for example, phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine, lipopolysaccharide.MSP evokes O(2)(-) production, cytokine release and NF-kappaB activation in a concentration-dependent manner. By evaluating the respiratory burst, we demonstrate a significantly increased O(2)(-) production in AM from healthy smokers or smokers with pulmonary fibrosis, as compared to non-smokers, thus suggesting MSP as an enhancer of cigarette smoke toxicity. Besides inducing interleukin-1 beta (IL-1beta) and interleukin-10 (IL-10) production, MSP triggers an enhanced tumor necrosis factor-alpha release, especially in healthy and pulmonary fibrosis smokers. On the contrary, MSP-induced IL-10 release is higher in AM from healthy non-smokers. MSP activates the transcription factor NF-kappaB; this effect is more potent in healthy and fibrosis smokers (2.5-fold increase in p50 subunit translocation). This effect is receptor-mediated, as it is prevented by a monoclonal anti-human MSP antibody. The higher effectiveness of MSP in AM from healthy smokers and patients with pulmonary fibrosis is suggestive of its role in these clinical conditions

  16. Effect of space flight on cytokine production

    Science.gov (United States)

    Sonnenfeld, Gerald

    Space flight has been shown to alter many immunological responses. Among those affected are the production of cytokines, Cytokines are the messengers of the immune system that facilitate communication among cells that allow the interaction among cells leading to the development of immune responses. Included among the cytokines are the interferons, interleukins, and colony stimulating factors. Cytokines also facilitate communication between the immune system and other body systems, such as the neuroendocrine and musculoskeletal systems. Some cytokines also have direct protective effects on the host, such as interferon, which can inhibit the replication of viruses. Studies in both humans and animals indicate that models of space flight as well as actual space flight alter the production and action of cytokines. Included among these changes are altered interferon production, altered responsiveness of bone marrow cells to granulocyte/monocyte-colony stimulating factor, but no alteration in the production of interleukin-3. This suggests that there are selective effects of space flight on immune responses, i.e. not all cytokines are affected in the same fashion by space flight. Tissue culture studies also suggest that there may be direct effects of space flight on the cells responsible for cytokine production and action. The results of the above study indicate that the effects of space flight on cytokines may be a fundamental mechanism by which space flight not only affects immune responses, but also other biological systems of the human.

  17. Analysis of surface roughness and surface heat affected zone of steel S355J0 after plasma arc cutting

    International Nuclear Information System (INIS)

    This paper deals with thermal cutting technology of materials with plasma arc. In the first part of this paper the theoretical knowledge of the principles of plasma arc cutting and current use of this technology in industry are presented. The cut of products with this technology is perpendicular and accurate, but the use of this technology affects micro-structural changes and depth of the heat affected zone (HAZ). This article deals with the experimental evaluation of plasma arc cutting technological process. The influence of technological factors on the roughness parameter Ra of the steel surface EN S355J0 has been evaluated by using planned experiments. By using the factor experiment, the significance of the four process factors such as plasma burner feed speed, plasma gas pressure, nozzle diameter, distance between nozzle mouth and material has been analyzed. Regression models obtained by multiple linear regression indicate the quality level of observed factors function. The heat from plasma arc cutting affects the micro-structural changes of the material, too.

  18. Cytokine Gene Polymorphisms support diagnostic monitoring of Romanian Multiple Myeloma patients

    OpenAIRE

    Banu, C; Moise, A; Arion, CV; Coriu, D.; T̆nase, A; Constantinescu, I

    2011-01-01

    Introduction: cytokines and their receptor genes are very polymorphic. SNPs in the promotor region of the gene may influence the rate of cytokine secretion and may affect the biological activity of the encoded cytokine. A number of cytokines and cytokine receptors have been directly linked to the development of human cancers. The aim of our study was to determine the cytokine gene polymorphism in Romanian multiple myeloma patients. Material and methods: cytokine genotyping was performed in 80...

  19. Novel methods of cytokine detection: Real-time PCR, ELISPOT, and intracellular cytokine staining

    Directory of Open Access Journals (Sweden)

    Eliza Turlej

    2009-05-01

    Full Text Available Cytokines are small hormone-like proteins that play important roles in immune system control. Cytokines regulate the proliferation and differentiation of cells and hematopoiesis and act as mediators in the inflammatory reaction. Changes in cytokine levels are found in many diseases, such as sepsis, bowel inflammatory disease, autoimmune diseases, as well as graft-versus-host disease. Cytokines levels can be detected using in vivo, in vitro, and ex vivo techniques. The level of cytokine produced can be measured by immunoenzymatic test (ELISA in supernatant after cell culture with the addition of stimulant and in plasma by techniques that measure the level of cytokine secretion in cells (e.g. immunohistochemical staining, ELISPOT, and intracellular cytokine staining, and by molecular biological methods (RPA, real-time PCR, in situ hybridization, and Northern blot. Detection of cytokine mRNA in tissues is useful in the direct determination of heterogenic populations of cytokine-producing cells. Nowadays the most frequently used methods for measuring cytokine level are ELISPOT, intracellular cytokine staining with flow cytometry detection, and real-time PCR. These methods have an important clinical role in vaccine efficacy, in viral, bacterial, and verminous diagnostics, and in determining the efficacy of cancer treatment.

  20. Cytokines as cellular communicators

    Directory of Open Access Journals (Sweden)

    R. Debets

    1996-01-01

    Full Text Available Cytokines and their receptors are involved in the pathophysiology of many diseases. Here we present a detailed review on cytokines, receptors and signalling routes, and show that one important lesson from cytokine biology is the complex and diverse regulation of cytokine activity. The activity of cytokines is controlled at the level of transcription, translation, storage, processing, posttranslational modification, trapping, binding by soluble proteins, and receptor number and/or function. Translation of this diverse regulation in strategies aimed at the control of cytokine activity will result in the development of more specific and selective drugs to treat diseases.

  1. Cytokines and brain excitability

    OpenAIRE

    Galic, Michael A.; Riazi, Kiarash; Pittman, Quentin J.

    2011-01-01

    Cytokines are molecules secreted by peripheral immune cells, microglia, astrocytes and neurons in the central nervous system. Peripheral or central inflammation is characterized by an upregulation of cytokines and their receptors in the brain. Emerging evidence indicates that pro-inflammatory cytokines modulate brain excitability. Findings from both the clinical literature and from in vivo and in vitro laboratory studies suggest that cytokines can increase seizure susceptibility and may be in...

  2. The impact of acute stress on hormones and cytokines, and how their recovery is affected by music-evoked positive mood

    OpenAIRE

    Stefan Koelsch; Albrecht Boehlig; Maximilian Hohenadel; Ines Nitsche; Katrin Bauer; Ulrich Sack

    2016-01-01

    Stress and recovery from stress significantly affect interactions between the central nervous system, endocrine pathways, and the immune system. However, the influence of acute stress on circulating immune-endocrine mediators in humans is not well known. Using a double-blind, randomized study design, we administered a CO2 stress test to n = 143 participants to identify the effects of acute stress, and recovery from stress, on serum levels of several mediators with immune function (IL-6, TNF-α...

  3. A lignan complex isolated from flaxseed does not affect plasma lipid concentrations or antioxidant capacity in healthy postmenopausal women

    DEFF Research Database (Denmark)

    Hallund, Jesper; Ravn-Haren, Gitte; Bügel, S.; Tholstrup, T.; Tetens, Inge

    2006-01-01

    ) completed a randomized, double-blind, placebo-controlled, crossover study. Women consumed daily a low-fat muffin, with or without a lignan complex, for 6 wk, separated by a 6-wk washout period. Serum ENL concentration, urinary ENL excretion, plasma concentrations of total cholesterol (TC), LDL cholesterol.......001) and ENL urinary excretion (P <0.001) were significantly higher after the lignan complex intervention period compared with placebo. Plasma concentrations of TC, LDL-C, HDL-C, TAG, lipoprotein oxidation lag time, TEAC and FRAP were not affected. Daily consumption for 6 wk of a low-fat muffin enriched...

  4. Plasma sprayed cylinder lining coatings : Factors affecting the amount of ceramics in plasma sprayed cylinder lining coatings

    OpenAIRE

    Antonsson Nilsson, Hermina; Jarnerud, Tova

    2015-01-01

    Scania uses powder plasma spray technology to coat their cylinder linings. The powder used contains stainless steel and ceramics. In order for the properties of the coating to reach the quality demands, it has to have a certain amount of pores and ceramics in it. Despite the process being strictly controlled the coating has proven to exhibit differences in composition. Process parameters for each coated lining are logged and as part of Scania’s quality control, samples of the coating are freq...

  5. Cytokines and the Skin Barrier

    Directory of Open Access Journals (Sweden)

    Jens Malte Baron

    2013-03-01

    Full Text Available The skin is the largest organ of the human body and builds a barrier to protect us from the harmful environment and also from unregulated loss of water. Keratinocytes form the skin barrier by undergoing a highly complex differentiation process that involves changing their morphology and structural integrity, a process referred to as cornification. Alterations in the epidermal cornification process affect the formation of the skin barrier. Typically, this results in a disturbed barrier, which allows the entry of substances into the skin that are immunologically reactive. This contributes to and promotes inflammatory processes in the skin but also affects other organs. In many common skin diseases, including atopic dermatitis and psoriasis, a defect in the formation of the skin barrier is observed. In these diseases the cytokine composition within the skin is different compared to normal human skin. This is the result of resident skin cells that produce cytokines, but also because additional immune cells are recruited. Many of the cytokines found in defective skin are able to influence various processes of differentiation and cornification. Here we summarize the current knowledge on cytokines and their functions in healthy skin and their contributions to inflammatory skin diseases.

  6. RNAi-mediated downregulation of poplar plasma membrane intrinsic proteins (PIPs) changes plasma membrane proteome composition and affects leaf physiology.

    Science.gov (United States)

    Bi, Zhen; Merl-Pham, Juliane; Uehlein, Norbert; Zimmer, Ina; Mühlhans, Stefanie; Aichler, Michaela; Walch, Axel Karl; Kaldenhoff, Ralf; Palme, Klaus; Schnitzler, Jörg-Peter; Block, Katja

    2015-10-14

    Plasma membrane intrinsic proteins (PIPs) are one subfamily of aquaporins that mediate the transmembrane transport of water. To reveal their function in poplar, we generated transgenic poplar plants in which the translation of PIP genes was downregulated by RNA interference investigated these plants with a comprehensive leaf plasma membrane proteome and physiome analysis. First, inhibition of PIP synthesis strongly altered the leaf plasma membrane protein composition. Strikingly, several signaling components and transporters involved in the regulation of stomatal movement were differentially regulated in transgenic poplars. Furthermore, hormonal crosstalk related to abscisic acid, auxin and brassinosteroids was altered, in addition to cell wall biosynthesis/cutinization, the organization of cellular structures and membrane trafficking. A physiological analysis confirmed the proteomic results. The leaves had wider opened stomata and higher net CO2 assimilation and transpiration rates as well as greater mesophyll conductance for CO2 (gm) and leaf hydraulic conductance (Kleaf). Based on these results, we conclude that PIP proteins not only play essential roles in whole leaf water and CO2 flux but have important roles in the regulation of stomatal movement. PMID:26248320

  7. The impact of acute stress on hormones and cytokines, and how their recovery is affected by music-evoked positive mood

    Science.gov (United States)

    Koelsch, Stefan; Boehlig, Albrecht; Hohenadel, Maximilian; Nitsche, Ines; Bauer, Katrin; Sack, Ulrich

    2016-01-01

    Stress and recovery from stress significantly affect interactions between the central nervous system, endocrine pathways, and the immune system. However, the influence of acute stress on circulating immune-endocrine mediators in humans is not well known. Using a double-blind, randomized study design, we administered a CO2 stress test to n = 143 participants to identify the effects of acute stress, and recovery from stress, on serum levels of several mediators with immune function (IL-6, TNF-α, leptin, and somatostatin), as well as on noradrenaline, and two hypothalamic–pituitary–adrenal axis hormones (ACTH and cortisol). Moreover, during a 1 h-recovery period, we repeatedly measured these serum parameters, and administered an auditory mood-induction protocol with positive music and a neutral control stimulus. The acute stress elicited increases in noradrenaline, ACTH, cortisol, IL-6, and leptin levels. Noradrenaline and ACTH exhibited the fastest and strongest stress responses, followed by cortisol, IL-6 and leptin. The music intervention was associated with more positive mood, and stronger cortisol responses to the acute stressor in the music group. Our data show that acute (CO2) stress affects endocrine, immune and metabolic functions in humans, and they show that mood plays a causal role in the modulation of responses to acute stress. PMID:27020850

  8. The impact of acute stress on hormones and cytokines, and how their recovery is affected by music-evoked positive mood.

    Science.gov (United States)

    Koelsch, Stefan; Boehlig, Albrecht; Hohenadel, Maximilian; Nitsche, Ines; Bauer, Katrin; Sack, Ulrich

    2016-01-01

    Stress and recovery from stress significantly affect interactions between the central nervous system, endocrine pathways, and the immune system. However, the influence of acute stress on circulating immune-endocrine mediators in humans is not well known. Using a double-blind, randomized study design, we administered a CO2 stress test to n = 143 participants to identify the effects of acute stress, and recovery from stress, on serum levels of several mediators with immune function (IL-6, TNF-α, leptin, and somatostatin), as well as on noradrenaline, and two hypothalamic-pituitary-adrenal axis hormones (ACTH and cortisol). Moreover, during a 1 h-recovery period, we repeatedly measured these serum parameters, and administered an auditory mood-induction protocol with positive music and a neutral control stimulus. The acute stress elicited increases in noradrenaline, ACTH, cortisol, IL-6, and leptin levels. Noradrenaline and ACTH exhibited the fastest and strongest stress responses, followed by cortisol, IL-6 and leptin. The music intervention was associated with more positive mood, and stronger cortisol responses to the acute stressor in the music group. Our data show that acute (CO2) stress affects endocrine, immune and metabolic functions in humans, and they show that mood plays a causal role in the modulation of responses to acute stress. PMID:27020850

  9. Vitamin E and omega-3 fatty acids independently attenuate plasma concentrations of proinflammatory cytokines and prostaglandin E3 in Escherichia coli lipopolysaccharide-challenged growing-finishing pigs.

    Science.gov (United States)

    Upadhaya, S D; Kim, J C; Mullan, B P; Pluske, J R; Kim, I H

    2015-06-01

    This study tested the hypothesis that vitamin E (Vit E) and omega-3 fatty acids will additively attenuate the production of proinflammatory cytokines and PGE2 in immune system–stimulated growing–finishing pigs. A total of 80 mixed sex pigs weighing 50.7 ± 0.76 kg (mean ± SE) were blocked and stratified based on sex and BW to a 2 × 2 factorial design with the respective factors being 1) without and with 300 IU Vit E and 2) without and with 25% replacement of tallow to linseed oil as a source of n-3 fatty acids. Each treatment consisted of 4 replicate pens with 5 pigs (3 barrows and 2 gilts) per pen. All pigs were challenged with an intramuscular injection of Escherichia coli lipopolysaccharide (LPS; O111:B4) twice weekly over the 6-wk experiment. After LPS challenge, pigs fed a diet supplemented with n-3 fatty acids had fewer (P fatty acids reduced (P fatty acids; however, the extent of the reduction was greater (P fatty acid–supplemented diet. However, there were no additive effects of the combined supplementation of Vit E and n-3 fatty acids on serum concentrations of proinflammatory cytokines and PGE2. The results suggest that n-3 fatty acids independently attenuate production of TNF-α and PGE2 in immune system–stimulated growing–finishing pigs. PMID:26115279

  10. Therapeutic potential for cytokine antagonists: Thalidomide and pentoxifylline in Hansen’s disease

    OpenAIRE

    1995-01-01

    Cytokine antagonists are a group of drugs defined by their actions on specific cytokines. Cytokine antagonists can inhibit action of cytokines by acting directly on receptors, by affecting production of cytokines or by binding to cytokines and preventing their subsequent action. Recent evidence suggests that Hansen’s disease, which is characterized by reactional states, is associated with elevated serum levels of tumour necrosis factor-α (tnf-α) and interleukin-1β during these reactional stat...

  11. Plasma taurine levels are not affected by vigabatrin in pediatric patients.

    Science.gov (United States)

    Spelbrink, Emily M; Mabud, Tarub S; Reimer, Richard; Porter, Brenda E

    2016-08-01

    Vigabatrin is a highly effective antiseizure medication, but its use is limited due to concerns about retinal toxicity. One proposed mechanism for this toxicity is vigabatrin-mediated reduction of taurine. Herein we assess plasma taurine levels in a retrospective cohort of children with epilepsy, including a subset receiving vigabatrin. All children who underwent a plasma amino acid analysis as part of their clinical evaluation between 2006 and 2015 at Stanford Children's Health were included in the analysis. There were no significant differences in plasma taurine levels between children taking vigabatrin (n = 16), children taking other anti-seizure medications, and children not taking any anti-seizure medication (n = 556) (analysis of variance [ANOVA] p = 0.841). There were, however, age-dependent decreases in plasma taurine levels. Multiple linear regression revealed no significant association between vigabatrin use and plasma taurine level (p = 0.87) when controlling for age. These results suggest that children taking vigabatrin maintain normal plasma taurine levels, although they leave unanswered whether taurine supplementation is necessary or sufficient to prevent vigabatrin-associated visual field loss. They also indicate that age should be taken into consideration when evaluating taurine levels in young children. PMID:27344989

  12. Seminal plasma applied post-thawing affects boar sperm physiology: a flow cytometry study.

    Science.gov (United States)

    Fernández-Gago, Rocío; Domínguez, Juan Carlos; Martínez-Pastor, Felipe

    2013-09-01

    Cryopreservation induces extensive biophysical and biochemical changes in the sperm. In the present study, we used flow cytometry to assess the capacitation-like status of frozen-thawed boar spermatozoa and its relationship with intracellular calcium, assessment of membrane fluidity, modification of thiol groups in plasma membrane proteins, reactive oxygen species (ROS) levels, viability, acrosomal status, and mitochondrial activity. This experiment was performed to verify the effect of adding seminal plasma on post-thaw sperm functions. To determine these effects after cryopreservation, frozen-thawed semen from seven boars was examined after supplementation with different concentrations of pooled seminal plasma (0%, 10%, and 50%) at various times of incubation from 0 to 4 hours. Incubation caused a decrease in membrane integrity and an increase in acrosomal damage, with small changes in other parameters (P > 0.05). Although 10% seminal plasma showed few differences with 0% (ROS increase at 4 hours, P boar spermatozoa, possibly through membrane changes and ROS increase. Although some effects were detrimental, the stimulatory effect of 50% seminal plasma could favor the performance of post-thawed boar semen, as showed in the field (García JC, Domínguez JC, Peña FJ, Alegre B, Gonzalez R, Castro MJ, Habing GG, Kirkwood RN. Thawing boar semen in the presence of seminal plasma: effects on sperm quality and fertility. Anim Reprod Sci 2010;119:160-5). PMID:23756043

  13. Plasma of Argon Affects the Earliest Biological Response of Different Implant Surfaces: An In Vitro Comparative Study.

    Science.gov (United States)

    Canullo, L; Genova, T; Tallarico, M; Gautier, G; Mussano, F; Botticelli, D

    2016-05-01

    The aim of this in vitro study was to evaluate the early cell response and protein adsorption elicited by the argon plasma treatment of different commercially available titanium surfaces via a chair-side device. Sterile disks made of grade 4 titanium (n= 450, 4-mm diameter) with 3 surface topographies (machined, plasma sprayed, and zirconia blasted and acid etched) were allocated to receive 4 testing treatments (2% and 10% protein adsorption and cell adhesion with MC3T3-E1 and MG-63). Furthermore, the specimens were divided to undergo 1) argon plasma treatment (10 W, 1 bar for 12 min) in a plasma reactor, 2) ultraviolet (UV) light treatment for 2 h (positive control group), or 3) no treatment (control group). Pretreatment surface analyses based on a scanning electron microscope and profilometer images were also performed. Profilometric analysis demonstrated that the evaluated specimens perfectly suit the standard parameters. The use of argon plasma was capable of affecting the quantity of proteins adsorbed on the different surfaces, notwithstanding their roughness or topographic features at a low fetal bovine serum concentration (2%). UV light treatment for 2 h attained similar results. Moreover, both the plasma of argon and the UV light demonstrated a significant increase in the number of osteoblasts adherent at 10 min in all tested surfaces. Within its limitations, this in vitro study highlights the potential biological benefits of treating implant surfaces with plasma of argon or UV, irrespective of the roughness of the titanium surface. However, in vivo experiments are needed to confirm these preliminary data and settle the rationale of a treatment that might be clinically relevant in case of bone-reparative deficiencies. PMID:26848069

  14. Changes in proinflammatory cytokine activity after menopause.

    Science.gov (United States)

    Pfeilschifter, Johannes; Köditz, Roland; Pfohl, Martin; Schatz, Helmut

    2002-02-01

    There is now a large body of evidence suggesting that the decline in ovarian function with menopause is associated with spontaneous increases in proinflammatory cytokines. The cytokines that have obtained the most attention are IL-1, IL-6, and TNF-alpha. The exact mechanisms by which estrogen interferes with cytokine activity are still incompletely known but may potentially include interactions of the ER with other transcription factors, modulation of nitric oxide activity, antioxidative effects, plasma membrane actions, and changes in immune cell function. Experimental and clinical studies strongly support a link between the increased state of proinflammatory cytokine activity and postmenopausal bone loss. Preliminary evidence suggests that these changes also might be relevant to vascular homeostasis and the development of atherosclerosis. Better knowledge of the mechanisms and the time course of these interactions may open new avenues for the prevention and treatment of some of the most prevalent and important disorders in postmenopausal women. PMID:11844745

  15. The Matrigel Cytokine Assay

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Ole Audun Haabeth, Bjarne Bogen & Alexandre Corthay ### Abstract Cytokines represent a diverse group of soluble proteins that play a key role in a number of physiological processes, including regulation of both the innate and adaptive immune responses. Cytokines are generally secreted in small amounts, and are relatively unstable. Therefore, detection and measurement of cytokine local concentrations in a tissue extracellular matrix can be challenging. To investigate cytok...

  16. Cytokines in psoriasis.

    Science.gov (United States)

    Baliwag, Jaymie; Barnes, Drew H; Johnston, Andrew

    2015-06-01

    Psoriasis is a common inflammatory skin disease with an incompletely understood etiology. The disease is characterized by red, scaly and well-demarcated skin lesions formed by the hyperproliferation of epidermal keratinocytes. This hyperproliferation is driven by cytokines secreted by activated resident immune cells, an infiltrate of T cells, dendritic cells and cells of the innate immune system, as well as the keratinocytes themselves. Psoriasis has a strong hereditary character and has a complex genetic background. Genome-wide association studies have identified polymorphisms within or near a number of genes encoding cytokines, cytokine receptors or elements of their signal transduction pathways, further implicating these cytokines in the psoriasis pathomechanism. A considerable number of inflammatory cytokines have been shown to be elevated in lesional psoriasis skin, and the serum concentrations of a subset of these also correlate with psoriasis disease severity. The combined effects of the cytokines found in psoriasis lesions likely explain most of the clinical features of psoriasis, such as the hyperproliferation of keratinocytes, increased neovascularization and skin inflammation. Thus, understanding which cytokines play a pivotal role in the disease process can suggest potential therapeutic targets. A number of cytokines have been therapeutically targeted with success, revolutionizing treatment of this disease. Here we review a number of key cytokines implicated in the pathogenesis of psoriasis. PMID:25585875

  17. Treatment of Cancer Pain by Targeting Cytokines

    OpenAIRE

    Vendrell, I.; Macedo, D.; Alho, I.; Dionísio, M. R.; Costa, L.

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be relate...

  18. HAEMATOLOGICAL VALUES AND PLASMA CHOLESTEROL AS AFFECTED BY MOULTING IN NICK CHICK LAYING HENS

    OpenAIRE

    Bashir Mahmood Bhatti and Tanzeela Talat

    2001-01-01

    This study was conducted to examine effect of moulting on haematological values and plasma cholesterol levels of 86 weeks old Nick Chick laying hens. Washington and California moulting methods were used. Young laying hens, 40 weeks old served as control group. There were 408 hens in each group. There was no significant (P

  19. Plasma membrane lipid-protein interactions affect signaling processes in sterol-biosynthesis mutants of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Henrik eZauber

    2014-03-01

    Full Text Available The plasma membrane is an important organelle providing structure, signaling and transport as major biological functions. Being composed of lipids and proteins with different physicochemical properties, the biological functions of membranes depend on specific protein-protein and protein-lipid interactions. Interactions of proteins with their specific sterol and lipid environment were shown to be important factors for protein recruitment into sub-compartmental structures of the plasma membrane. System-wide implications of altered endogenous sterol levels for membrane functions in living cells were not studied in higher plant cells. In particular, little is known how alterations in membrane sterol composition affect protein and lipid organization and interaction within membranes. Here, we conducted a comparative analysis of the plasma membrane protein and lipid composition in Arabidopsis sterol-biosynthesis mutants smt1 and ugt80A2;B1. smt1 shows general alterations in sterol composition while ugt80A2;B1 is significantly impaired in sterol glycosylation. By systematically analyzing different cellular fractions and combining proteomic with lipidomic data we were able to reveal contrasting alterations in lipid-protein interactions in both mutants, with resulting differential changes in plasma membrane signaling status.

  20. Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte Behavior In Vitro

    OpenAIRE

    Ilaria Giusti; Sandra D’Ascenzo; Annalisa Mancò; Gabriella Di Stefano; Marianna Di Francesco; Anna Rughetti; Antonella Dal Mas; Gianfranco Properzi; Vittorio Calvisi; Vincenza Dolo

    2014-01-01

    Since tendon injuries and tendinopathy are a growing problem, sometimes requiring surgery, new strategies that improve conservative therapies are needed. Platelet-rich plasma (PRP) seems to be a good candidate by virtue of its high content of growth factors, most of which are involved in tendon healing. This study aimed to evaluate if different concentrations of platelets in PRP have different effects on the biological features of normal human tenocytes that are usually required during tendon...

  1. Inhibition of sphingomyelin synthase (SMS) affects intracellular sphingomyelin accumulation and plasma membrane lipid organization

    OpenAIRE

    Li, Zhiqiang; Hailemariam, Tiruneh K.; Zhou, Hongwen; Li, Yan; Duckworth, Dale C.; Peake, David A.; Zhang, Youyan; Kuo, Ming-Shang; Cao, Guoqing; Jiang, Xian-Cheng

    2007-01-01

    Sphingomyelin plays a very important role both in cell membrane formation that may well have an impact on the development of diseases like atherosclerosis and diabetes. However, the molecular mechanism that governs intracellular and plasma membrane SM levels is largely unknown. Recently, two isoforms of sphingomyelin synthase (SMS1 and SMS2), the last enzyme for SM de novo synthesis, have been cloned. We have hypothesized that SMS1 and SMS2 are the two most likely candidates responsible for t...

  2. Nature of sterols affects plasma membrane behavior and yeast survival during dehydration.

    OpenAIRE

    Dupont, Sébastien; Beney, Laurent; Ferreira, Thierry; Gervais, Patrick

    2011-01-01

    The plasma membrane (PM) is a main site of injury during osmotic perturbation. Sterols, major lipids of the PM structure in eukaryotes, are thought to play a role in ensuring the stability of the lipid bilayer during physicochemical perturbations. Here, we investigated the relationship between the nature of PM sterols and resistance of the yeast Saccharomyces cerevisiae to hyperosmotic treatment. We compared the responses to osmotic dehydration (viability, sterol quantification, ultrastructur...

  3. Plasma Procalcitonin Concentration in Healthy Horses and Horses Affected by Systemic Inflammatory Response Syndrome

    OpenAIRE

    Bonelli, F.; Meucci, V.; Divers, T.J.; Jose‐Cunilleras, E.; Corazza, M; Tognetti, R; Guidi, G.; Intorre, L.; Sgorbini, M.

    2015-01-01

    Background The diseases most frequent associated with SIRS in adult horses are those involving the gastrointestinal tract. An early diagnosis should be the goal in the management of horses with SIRS. Objective The objective of this study was to evaluate the plasma procalcitonin (PCT) concentration in healthy and SIRS horses to assess differences between the two groups. Animals Seventy‐eight horses (30 healthy and 48 SIRS). Methods Prospective in vivo multicentric study. Horses were classified...

  4. Long-term high fructose and saturated fat diet affects plasma fatty acid profile in rats

    Institute of Scientific and Technical Information of China (English)

    Fabrice TRANCHIDA; Léopold TCHIAKPE; Zo RAKOTONIAINA; Valérie DEYRIS; Olivier RAVION; Abel HIOL

    2012-01-01

    As the consumption of fructose and saturated fatty acids (FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome,the aim of this study was to investigate the effects of a moderate (10 weeks) and a prolonged (30 weeks) high fructose and saturated fatty acid (HFS) diet on plasma FA composition in rats.The effects of a few weeks of HFS diet had already been described,but in this paper we tried to establish whether these effects persist or if they are modified after 10 or 30 weeks.We hypothesized that the plasma FA profile would be altered between 10 and 30 weeks of the HFS diet.Rats fed with either the HFS or a standard diet were tested after 10 weeks and again after 30 weeks.After 10 weeks of feeding,HFS-fed rats developed the metabolic syndrome,as manifested by an increase in fasting insulinemia,total cholesterol and triglyceride levels,as well as by impaired glucose tolerance.Furthermore,the plasma FA profile of the HFS group showed higher proportions of monounsaturated FAs like palmitoleic acid [16:1(n-7)] and oleic acid [18:1(n-9)],whereas the proportions of some polyunsaturated n-6 FAs,such as linoleic acid [18:2(n-6)] and arachidonic acid [20:4(n-6)],were lower than those in the control group.After 30 weeks of the HFS diet,we observed changes mainly in the levels of 16:1(n-7) (decreased)and 20:4(n-6) (increased).Together,our results suggest that an HFS diet could lead to an adaptive response of the plasma FA profile over time,in association with the development of the metabolic syndrome.

  5. Altered plasma pharmacokinetics of ceftiofur hydrochloride in cows affected with severe clinical mastitis.

    Science.gov (United States)

    Gorden, P J; Kleinhenz, M D; Wulf, L W; KuKanich, B; Lee, C J; Wang, C; Coetzee, J F

    2016-01-01

    Mastitis is a frequent problem among dairy cows, reducing milk yield and increasing cull rates. Systemic therapy with the cephalosporin antimicrobial ceftiofur hydrochloride (CEF) may improve therapeutic outcomes, but the incidence of CEF violative residues has increased annually since 2011. One potential explanation is that disease status may alter the pharmacokinetics (PK) of CEF. To test this hypothesis, we compared the plasma PK of CEF in healthy cows with those with severe endotoxic mastitis. Eight cows with naturally occurring mastitis and 8 clinically healthy cows were treated with 2.2 mg of CEF per kilogram of body weight once daily for 5d via the intramuscular route. Blood was collected at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 8, 16, and 24h after the first CEF administration and every 8h thereafter until 120 h after the final dose. Plasma samples were analyzed for CEF concentrations using liquid chromatography coupled with mass spectrometry. With the exception of time 0, CEF was detected at all time points. The disease group had a significantly higher plasma CEF concentration at t=3h after the first injection and a significantly lower plasma concentration from 40 to 152 h following the first injection, with the exception of the t=64 h time point. Data following the first injection (time 0-24 h) were fit to a single-dose, noncompartmental PK model. This model indicated that the disease group had a shorter plasma half-life. A multidose, noncompartmental model was used to determine steady-state PK. Compared with control cows, the disease group had an initially higher peak concentration and a higher volume of distribution and drug clearance rates. The disease group also had a lower area under the curve per dosing interval, steady-state concentration maximum, and dose-adjusted peak steady-state concentration. All other PK parameters were not different between the 2 groups. Altered PK, as suggested by this trial, may contribute to an increased risk for the

  6. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Hoejman, Pernille;

    2015-01-01

    UNLABELLED: The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant...... depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU) or...

  7. Kiwifruit consumption favourably affects plasma lipids in a randomised controlled trial in hypercholesterolaemic men.

    Science.gov (United States)

    Gammon, Cheryl S; Kruger, Rozanne; Minihane, Anne M; Conlon, Cathryn A; von Hurst, Pamela R; Stonehouse, Welma

    2013-06-28

    The unique composition of green kiwifruit has the potential to benefit CVD risk. The aim of the present study was to investigate the effect of consuming two green kiwifruits daily in conjunction with a healthy diet on plasma lipids and other metabolic markers and to examine response according to APOE genotype in hypercholesterolaemic men. After undergoing a 4-week healthy diet, eighty-five hypercholesterolaemic men (LDL-cholesterol (LDL-C) > 3.0 mmol/l and TAG < 3 mmol/l) completed an 8-week randomised controlled cross-over study of two 4-week intervention sequences of two green kiwifruits per d plus healthy diet (intervention) or healthy diet alone (control). Anthropometric measures, blood pressure (BP) and fasting blood samples (plasma lipids, serum apoA1 and apoB, insulin, glucose, high-sensitivity C-reactive protein (hs-CRP)) were taken at baseline, and at 4 and 8 weeks. After the kiwifruit intervention, plasma HDL-cholesterol (HDL-C) concentrations were significantly higher (mean difference 0.04; 95% CI 0.01, 0.07 mmol/l; P = 0.004) and the total cholesterol (TC):HDL-C ratio was significantly lower (mean difference 20.5; 95% CI 20.24, 20.05 mmol/l; P = 0.002) compared with the control. In carriers of the APOE4 allele, TAG decreased significantly (mean difference -0.18; 95% CI -0.34, -0.02 mol/l; P = 0.03) with kiwifruit compared with control. There were no significant differences between the two interventions for plasma TC, LDL-C, insulin, glucose, hs-CRP and BP. The small but significant increase in HDL-C and decrease in TC:HDL-C ratio and TAG (in APOE4 carriers) suggest that the regular inclusion of green kiwifruit as part of a healthy diet may be beneficial in improving the lipid profiles of men with high cholesterol. PMID:23151354

  8. [Cytokines and osteogenesis].

    Science.gov (United States)

    Fujiwara, Makoto; Ozono, Keiichi

    2014-06-01

    Many cytokines associate with proliferation, differentiation and activation of osteoblasts which have an important role in osteogenesis. TGF-β, BMP, IGF, FGF, Hedgehog, Notch, IL and WNT signaling pathways and their inhibitors have been revealed to correlate to osteogenesis, and those gene mutations have been shown to cause various bone disorders. It has been suggested that there are common pathways or crosstalk in these cytokine signaling each other, but mechanism of their complicated regulation on osteogenesis has been unclear. It was expected that the knowledge about these cytokines will apply to clinical therapies of bone diseases. PMID:24870835

  9. Radial thermal diffusivity of toroidal plasma affected by resonant magnetic perturbations

    International Nuclear Information System (INIS)

    We investigate how the radial thermal diffusivity of an axisymmetric toroidal plasma is modified by effect of resonant magnetic perturbations (RMPs), using a drift kinetic simulation code for calculating the thermal diffusivity in the perturbed region. The perturbed region is assumed to be generated on and around the resonance surfaces, and is wedged in between the regular closed magnetic surfaces. It has been found that the radial thermal diffusivity χr in the perturbed region is represented as χr = χr(0) {1 + c r parallel2>}. Here r parallel2>1/2 is the strength of the RMPs in the radial directions, means the flux surface average defined by the unperturbed (i.e., original) magnetic field, χr(0) is the neoclassical thermal diffusivity, and c is a positive coefficient. In this paper, dependence of the coefficient c on parameters of the toroidal plasma is studied in results given by the δ f simulation code solving the drift kinetic equation under an assumption of zero electric field. We find that the dependence of c is given as c ∝ ωb/νeff m in the low collisionality regime νeff b, where νeff is the effective collision frequency, ωb is the bounce frequency and m is the particle mass. In case of νeff > ωb, the thermal diffusivity χr evaluated by the simulations becomes close to the neoclassical thermal diffusivity χr(0). (author)

  10. Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

    Directory of Open Access Journals (Sweden)

    Gozzo A.J.

    2003-01-01

    Full Text Available Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates reduced (1.2 to 3.0 times the catalytic efficiency of kallikrein (in a nanomolar range on the hydrolysis of plasminogen (0.3 to 1.8 µM and increased (1.9 to 7.7 times the enzyme efficiency in factor XII (0.1 to 10 µM activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times kallikrein inhibition by antithrombin (1.4 µM, while chondroitin 4- and 6-sulfates reduced it (1.3 times. Heparin and heparan sulfate increased (1.4 times the enzyme inhibition by the C1-inhibitor (150 nM.

  11. Censored correlated cytokine concentrations

    DEFF Research Database (Denmark)

    Andersen, Andreas; Benn, Christine Stabell; Jørgensen, Mathias J;

    2013-01-01

    Interest in cytokines as markers for the function of the immune system is increasing. Methods quantifying cytokine concentrations are often subject to detection limits, which lead to non-detectable observations and censored distributions. When distributions are skewed, geometric mean ratios (GMRs......) can be used to describe the relative concentration between two cytokines, and the GMR ratio (GMRR) can be used to compare two groups. The problem is how to estimate GMRRs from censored distributions.We evaluated methods, including simple deletion and substitution, in simulated and real data. One...... method applies Tobit directly to the censored difference between the two cytokine log-concentrations (Diff). However, censoring is correlated to the outcome and is therefore not independent. The correlation increases as the correlation between the two log-concentrations decreases. We propose a Tobit...

  12. [Immunostimulating drugs and cytokines].

    Science.gov (United States)

    Lehners, Nicola; Goldschmidt, Hartmut; Raab, Marc S

    2011-11-01

    Cytokines are essential regulators of hematopoesis and the immune system. Genetic engineering of recombinant cytokines has facilitated their implementation in many clinical areas. In the field of oncology the granulopoetic human growth factors G-CSF and GM-CSF are of particular importance. They can be applied to prevent chemotherapy induced neutropenia. Furthermore, they allow for mobilization of hematopoetic stem cells in order to obtain peripheral blood stem cell transplants. Another class of cytokines, the interferons, possess immunomodulating, antiproliferative, and antiviral properties. While the significance of interferon alfa as an antitumor agent is dwindling, it still plays a very important role in the therapy of chronic hepatitis b and c. Interferon beta is successfully used to treat multiple sclerosis. Among the heterogenous group of interleukines in particular interleukin 2 has reached clinical practice as an immunostimulating agent in the therapy of metastatic renal cell carcinoma. Many other cytokines have yet to undergo clinical trials. PMID:22045528

  13. Recombinant Cytokines from Plants

    OpenAIRE

    Patrycja Redkiewicz; Anna Góra-Sochacka; Tomas Vaněk; Agnieszka Sirko

    2011-01-01

    Plant-based platforms have been successfully applied for the last two decades for the efficient production of pharmaceutical proteins. The number of commercialized products biomanufactured in plants is, however, rather discouraging. Cytokines are small glycosylated polypeptides used in the treatment of cancer, immune disorders and various other related diseases. Because the clinical use of cytokines is limited by high production costs they are good candidates for plant-made pharmaceuticals. S...

  14. Does the plasma composition affect the long term evolution of relativistic jets?

    CERN Document Server

    Scheck, L; Martí, J M; Gómez, J L; Müller, E

    2002-01-01

    We study the influence of the matter content of extragalactic jets on their morphology, dynamics and emission properties. For this purpose we consider jets of extremely different compositions including pure leptonic and baryonic plasmas. Our work is based on two-dimensional relativistic hydrodynamic simulations of the long-term evolution of powerful extragalactic jets propagating into a homogeneous environment. The equation of state used in the simulations accounts for an arbitrary mixture of electrons, protons and electron-positron pairs. Using the hydrodynamic models we have also computed synthetic radio maps and the thermal Bremsstrahlung X-ray emission from their cavities. Although there is a difference of about three orders of magnitude in the temperatures of the cavities inflated by the simulated jets, we find that both the morphology and the dynamic behaviour are almost independent on the assumed composition of the jets. Their evolution proceeds in two distinct epochs. During the first one multidimensi...

  15. Fish oil affects blood pressure and the plasma lipid profile in healthy Danish infants

    DEFF Research Database (Denmark)

    Damsgaard, C.T.; Schack-Nielsen, L.; Michaelsen, K.F.; Fruekilde, Maj-Britt; Hels, O.; Lauritzen, L.

    2006-01-01

    Animal and epidemiologic studies indicate that early nutrition has lasting effects on metabolism and cardiovascular disease risk. In adults, (n-3) long-chain PUFA (LCPUFA) from fish oils improve blood pressure, the lipid profile, and possibly cardiovascular disease mortality. This randomized trial...... is the first to investigate the effects of fish oil on blood pressure and the lipid profile in infancy. Healthy term 9-mo old infants In 83) were randomly assigned to 5 mL fish oil daily or no fish oil for 3 mo and to 2 different milk types. Before and after the intervention, blood pressure was...... measured with an oscillometric device, and blood was sampled for analysis of erythrocyte fatty acid composition and the plasma lipid profile. This paper examines the effects of the fish oil supplement, with adjustment for the effects of the milk intervention when relevant. The fish oil intervention...

  16. Evaluation of a feline-specific multiplex, bead-based assay for detection of cytokines, chemokines, growth factors, and other immunologically active proteins in serum and plasma samples from cats.

    Science.gov (United States)

    Halpin, Rachel E; Saunders, Rebecca S; Thompson, Beverly J; Rohde Newgent, Allison S; Amorim, Juliana; Melillo, Gabrielle N; DeClue, Amy E

    2016-05-01

    OBJECTIVE To evaluate a feline-specific multiplex, bead-based assay system for detection of recombinant and native proteins in serum samples and in EDTA-treated and heparinized plasma samples. SAMPLE Serum samples and EDTA-treated and heparinized plasma samples from 30 sick cats and 9 healthy client-owned cats and heparinized whole blood samples from 5 healthy purpose-bred cats. PROCEDURES Ability of the assay system to detect 19 recombinant and native immunologically active proteins in plasma and serum samples from healthy and purpose-bred cats was evaluated via spike-and-recovery tests, assessments of inter- and intra-assay variation, linearity results, and leukocyte stimulation. Effects of various concentrations of heparin and serum matrix solution on percentages of analytes recovered were also evaluated. Analyte concentrations in samples from healthy and sick cats were measured and compared between groups. RESULTS Percentages of analytes recovered were unsatisfactory for most assays. Serum and heparinized plasma samples yielded better recovery results than did EDTA-treated plasma samples. Use of serum matrix solution did not improve results. Use of heparin concentrations greater than the recommended range affected the results. Linearity of results was difficult to assess because of the poor recovery. For the analytes that were recovered sufficiently for assessment, linearity appeared to be reasonable despite the limited detection. CONCLUSIONS AND CLINICAL RELEVANCE Poor percentages of analytes recovered and adverse effects of sample protein matrix limited the usefulness of the multiplex, bead-based assay system for measurement of immunologically active proteins in solutions with high protein content; however, recovery results were fairly linear, potentially allowing evaluation of feline plasma or serum samples with high analyte concentrations. PMID:27111017

  17. Platelet concentration in platelet-rich plasma affects tenocyte behavior in vitro.

    Science.gov (United States)

    Giusti, Ilaria; D'Ascenzo, Sandra; Mancò, Annalisa; Di Stefano, Gabriella; Di Francesco, Marianna; Rughetti, Anna; Dal Mas, Antonella; Properzi, Gianfranco; Calvisi, Vittorio; Dolo, Vincenza

    2014-01-01

    Since tendon injuries and tendinopathy are a growing problem, sometimes requiring surgery, new strategies that improve conservative therapies are needed. Platelet-rich plasma (PRP) seems to be a good candidate by virtue of its high content of growth factors, most of which are involved in tendon healing. This study aimed to evaluate if different concentrations of platelets in PRP have different effects on the biological features of normal human tenocytes that are usually required during tendon healing. The different platelet concentrations tested (up to 5 × 10(6) plt/µL) stimulated differently tenocytes behavior; intermediate concentrations (0.5 × 10(6), 1 × 10(6) plt/µL) strongly induced all tested processes (proliferation, migration, collagen, and MMPs production) if compared to untreated cells; on the contrary, the highest concentration had inhibitory effects on proliferation and strongly reduced migration abilities and overall collagen production but, at the same time, induced increasing MMP production, which could be counterproductive because excessive proteolysis could impair tendon mechanical stability. Thus, these in vitro data strongly suggest the need for a compromise between extremely high and low platelet concentrations to obtain an optimal global effect when inducing in vivo tendon healing. PMID:25147809

  18. Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte Behavior In Vitro

    Directory of Open Access Journals (Sweden)

    Ilaria Giusti

    2014-01-01

    Full Text Available Since tendon injuries and tendinopathy are a growing problem, sometimes requiring surgery, new strategies that improve conservative therapies are needed. Platelet-rich plasma (PRP seems to be a good candidate by virtue of its high content of growth factors, most of which are involved in tendon healing. This study aimed to evaluate if different concentrations of platelets in PRP have different effects on the biological features of normal human tenocytes that are usually required during tendon healing. The different platelet concentrations tested (up to 5 × 106 plt/µL stimulated differently tenocytes behavior; intermediate concentrations (0.5 × 106, 1 × 106 plt/µL strongly induced all tested processes (proliferation, migration, collagen, and MMPs production if compared to untreated cells; on the contrary, the highest concentration had inhibitory effects on proliferation and strongly reduced migration abilities and overall collagen production but, at the same time, induced increasing MMP production, which could be counterproductive because excessive proteolysis could impair tendon mechanical stability. Thus, these in vitro data strongly suggest the need for a compromise between extremely high and low platelet concentrations to obtain an optimal global effect when inducing in vivo tendon healing.

  19. Infusion of hypertonic saline before elective hysterectomy: effects on cytokines and stress hormonesTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Kolsen-Petersen, J.A.; Bendtzen, K.; Tonnesen, E.

    2008-01-01

    BACKGROUND: Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery. METHODS: Sixty-two women undergoing abdominal hysterectomy were randomized in a...... with the other groups (P<0.05). No other differences were found between the groups. CONCLUSIONS: Infusion of a clinically relevant dose of hypertonic saline before hysterectomy appears to have limited effect on the postoperative concentration of selected plasma cytokines and the hormonal stress...

  20. Nanosecond electric pulses affect a plant-specific kinesin at the plasma membrane.

    Science.gov (United States)

    Kühn, Sebastian; Liu, Qiong; Eing, Christian; Frey, Wolfgang; Nick, Peter

    2013-12-01

    Electric pulses with high field strength and durations in the nanosecond range (nsPEFs) are of considerable interest for biotechnological and medical applications. However, their actual cellular site of action is still under debate--due to their extremely short rise times, nsPEFs are thought to act mainly in the cell interior rather than at the plasma membrane. On the other hand, nsPEFs can induce membrane permeability. We have revisited this issue using plant cells as a model. By mapping the cellular responses to nsPEFs of different field strength and duration in the tobacco BY-2 cell line, we could define a treatment that does not impinge on short-term viability, such that the physiological responses to the treatment can be followed. We observe, for these conditions, a mild disintegration of the cytoskeleton, impaired membrane localization of the PIN1 auxin-efflux transporter and a delayed premitotic nuclear positioning followed by a transient mitotic arrest. To address the target site of nsPEFs, we made use of the plant-specific KCH kinesin, which can assume two different states with different localization (either near the nucleus or at the cell membrane) driving different cellular functions. We show that nsPEFs reduce cell expansion in nontransformed cells but promote expansion in a line overexpressing KCH. Since cell elongation and cell widening are linked to the KCH localized at the cell membrane, the inverted response in the KCH overexpressor provides evidence for a direct action of nsPEFs, also at the cell membrane. PMID:24062185

  1. Numerical simulation of dispersive Alfvén wave turbulence in auroral plasmas affecting the Earth's communications

    International Nuclear Information System (INIS)

    This paper presents the numerical simulation of the model equation governing the nonlinear dynamics of dispersive Alfvén waves (DAWs) in low-β plasmas. When the nonlinearity arises due to the ponderomotive force and Joule heating-driven density perturbations, the model equation turns out to be a modified nonlinear Schrödinger (MNLS) equation. The nonlinear MNLS is used to investigate the evolution of a finite-amplitude localized initial perturbation. The initial perturbation is of the form of a sinusoidal pulse on a DAW having a Gaussian wavefront. The localized structures of DAWs with sidebands are obtained. Also, we have studied the power spectra of magnetic fluctuations with different scaling laws. These turbulent structures may be responsible for particle acceleration in the aurora region and may affect the Earth's communication.

  2. Dietary fat affects plasma prolactin in female F344 rats under conditions of ether stress.

    Science.gov (United States)

    Bosland, M C; Bunnik, G S; Wilbrink, B; de Bie, B T; Floor, B

    1994-01-01

    The influence of amount and type of dietary fat on circulating concentrations of prolactin and estradiol-17 beta in female F344 rats from which blood was sampled by decapitation under ether anesthesia was compared with that in rats from which blood was collected without anesthesia. The animals were fed isonutrient (adjusted for differences in energy density) semipurified diets containing 5% or 20% (by weight) sunflower seed oil or lard. Blood was sampled by decapitation with or without standardized ether anesthesia during the afternoon of proestrus-estrus or the morning of metestrus-diestrus, as determined by examination of vaginal smears. Plasma hormone concentrations were measured by radioimmunoassay. Prolactin levels were lower during proestrus-estrus in rats fed a low-fat diet than in animals fed a high-fat diet, statistically independent of the type of dietary fat, but only when blood was sampled by decapitation under ether anesthesia [p = 0.0384, 2-way analysis of variance (ANOVA)]. No such difference was found in rats decapitated without anesthesia. This effect of amount of dietary fat on prolactin in proestrus-estrus animals anesthetized with ether was predominantly present in animals fed polyunsaturated fat (p rats fed saturated fat diets. During metestrus-diestrus, prolactin levels were significantly lower in animals fed a high-saturated fat diet than in those fed low-saturated fat, low-unsaturated fat, or high-unsaturated fat diets, independent of the blood sampling conditions (p conversion efficiency was lower in animals fed low-fat diets than in those fed high-fat diets. This study confirms the hypothesis that effects of dietary fat, particularly polyunsaturated fat, on circulating prolactin occur only during (ether) stress. Because stress is a frequent and normal phenomenon, this observation implies that the mammary glands of animals with a high dietary intake of polyunsaturated fat are frequently exposed to higher circulating prolactin concentrations

  3. Pre-Analytical Parameters Affecting Vascular Endothelial Growth Factor Measurement in Plasma: Identifying Confounders.

    Directory of Open Access Journals (Sweden)

    Johanna M Walz

    Full Text Available Vascular endothelial growth factor-A (VEGF-A is intensively investigated in various medical fields. However, comparing VEGF-A measurements is difficult because sample acquisition and pre-analytic procedures differ between studies. We therefore investigated which variables act as confounders of VEGF-A measurements.Following a standardized protocol, blood was taken at three clinical sites from six healthy participants (one male and one female participant at each center twice one week apart. The following pre-analytical parameters were varied in order to analyze their impact on VEGF-A measurements: analyzing center, anticoagulant (EDTA vs. PECT / CTAD, cannula (butterfly vs. neonatal, type of centrifuge (swing-out vs. fixed-angle, time before and after centrifugation, filling level (completely filled vs. half-filled tubes and analyzing method (ELISA vs. multiplex bead array. Additionally, intrapersonal variations over time and sex differences were explored. Statistical analysis was performed using a linear regression model.The following parameters were identified as statistically significant independent confounders of VEGF-A measurements: analyzing center, anticoagulant, centrifuge, analyzing method and sex of the proband. The following parameters were no significant confounders in our data set: intrapersonal variation over one week, cannula, time before and after centrifugation and filling level of collection tubes.VEGF-A measurement results can be affected significantly by the identified pre-analytical parameters. We recommend the use of CTAD anticoagulant, a standardized type of centrifuge and one central laboratory using the same analyzing method for all samples.

  4. Recombinant Cytokines from Plants

    Czech Academy of Sciences Publication Activity Database

    Sirko, A.; Vaněk, Tomáš; Gora-Sochacka, A.; Redkiewicz, P.

    2011-01-01

    Roč. 12, č. 6 (2011), s. 3536-3552. ISSN 1661-6596 Institutional research plan: CEZ:AV0Z50380511 Keywords : cytokines * pharmaceutical proteins * plant-based production systems Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.598, year: 2011

  5. Cytokines and antitumor immunity.

    Science.gov (United States)

    Müller, Ludmila; Pawelec, Graham

    2003-06-01

    Currently, the notion of immunosurveillance against tumors is enjoying something of a renaissance. Even if we still refuse to accept that tumors arising in the normal host are unable to trigger an immune response because of the lack of initiation ("danger") signals, there is no doubt that the immune system can be manipulated experimentally and by implication therapeutically to exert anti-tumor effects. For this activity to be successful, the appropriate cytokine milieu has to be provided, making cytokine manipulation central to immunotherapy. On the other hand, the major hurdle currently preventing successful immunotherapy is the ability of tumors to evolve resistant variants under the pressure of immune selection. Here, too, the cytokine milieu plays an essential role. The purpose of this brief review is to consider the current status of the application of cytokines in facilitating antitumor immunity, as well their role in inhibiting responses to tumors. Clearly, encouraging the former but preventing the latter will be the key to the effective clinical application of cancer immunotherapy. PMID:12779349

  6. Cytokines and signaling molecules predict clinical outcomes in sepsis.

    Directory of Open Access Journals (Sweden)

    Christopher D Fjell

    Full Text Available INTRODUCTION: Inflammatory response during sepsis is incompletely understood due to small sample sizes and variable timing of measurements following the onset of symptoms. The vasopressin in septic shock trial (VASST compared the addition of vasopressin to norepinephrine alone in patients with septic shock. During this study plasma was collected and 39 cytokines measured in a 363 patients at both baseline (before treatment and 24 hours. Clinical features relating to both underlying health and the acute organ dysfunction induced by the severe infection were collected during the first 28 days of admission. HYPOTHESIS: Cluster analysis of cytokines identifies subgroups of patients at differing risk of death and organ failure. METHODS: Circulating cytokines and other signaling molecules were measured using a Luminex multi-bead analyte detection system. Hierarchical clustering was performed on plasma values to create patient subgroups. Enrichment analysis identified clinical outcomes significantly different according to these chemically defined patient subgroups. Logistic regression was performed to assess the importance of cytokines for predicting patient subgroups. RESULTS: Plasma levels at baseline produced three subgroups of patients, while 24 hour levels produced two subgroups. Using baseline cytokine data, one subgroup of 47 patients showed a high level of enrichment for severe septic shock, coagulopathy, renal failure, and risk of death. Using data at 24 hours, a larger subgroup of 81 patients that largely encompassed the 47 baseline subgroup patients had a similar enrichment profile. Measurement of two cytokines, IL2 and CSF2 and their product were sufficient to classify patients into these subgroups that defined clinical risks. CONCLUSIONS: A distinct pattern of cytokine levels measured early in the course of sepsis predicts disease outcome. Subpopulations of patients have differing clinical outcomes that can be predicted accurately from

  7. Cytokine signature profiles in acquired aplastic anemia and myelodysplastic syndromes

    OpenAIRE

    Feng, Xingmin; Scheinberg, Phillip; Wu, Colin O.; Samsel, Leigh; Nunez, Olga; Prince, Courtney; Ganetzky, Rebecca D.; McCoy, J. Philip; Maciejewski, Jaroslaw P.; Young, Neal S.

    2010-01-01

    Although aplastic anemia and myelodysplasia have been extensively investigated, little is known about their circulating cytokine patterns. We compared plasma soluble cytokines in 33 aplastic anemia, 57 myelodysplasia patients, and 48 healthy controls. High levels of thrombopoietin and granulocyte colony-stimulating factor, with low levels of CD40 ligand, chemokine (C-X-C motif) ligand 5, chemokine (C-C motif) ligand 5, chemokine (C-X-C motif) ligand 11, epidermal growth factor, vascular endot...

  8. Cytokines in bipolar disorder vs. healthy control subjects

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Braüner, Julie Vestergaard; Kessing, Lars Vedel;

    2013-01-01

    Bipolar disorder may be associated with peripheral immune system dysfunction; however, results in individual studies are conflicting. Our aim was to systematically review evidence of peripheral cytokine alterations in bipolar disorder integrating findings from various affective states....

  9. Plant cytokine or phytocytokine

    OpenAIRE

    Luo, Li

    2012-01-01

    Peptide hormones play an important role in plant growth and development. Some of them are secreted by stem cells and also regulate plant immunity through cell-cell communication and reprogramming the expression of immune related genes, such as CLAVATA3p (CLV3p) and phytosulfokine (PSK). These peptides play similar roles as cytokines in plant innate immunity. As explosive progress of plant omics, more and more such functional peptides will be discovered. I recommend that they should be named a...

  10. Multiparameter Intracellular Cytokine Staining

    OpenAIRE

    Lovelace, Patricia; Maecker, Holden T.

    2011-01-01

    Intracellular cytokine staining (ICS) is a popular method for visualizing cellular responses, most often T-cell responses to antigenic or mitogenic stimulation. It can be coupled with staining for other functional markers, such as upregulation of CD107 or CD154, as well as phenotypic markers that define specific cellular subsets, e.g. effector and memory T-cell compartments. Recent advances in multicolor flow cytometry instrumentation and software have allowed the routine combination of 8–12 ...

  11. Interactions between genetic variants of folate metabolism genes and lifestyle affect plasma homocysteine concentrations in the Boston Puerto Rican Population

    Science.gov (United States)

    Results of studies investigating relationships between lifestyle factors and elevated plasma homocysteine (Hcy), an independent risk factor for cardiovascular disease, are conflicting. The objective of this study was to investigate genetic and lifestyle factors and their interactions on plasma Hcy c...

  12. Lipid-based nutrient supplements do not affect efavirenz but lower plasma nevirapine concentrations in Ethiopian adult HIV patients

    DEFF Research Database (Denmark)

    Abdissa, A; Olsen, Mette Frahm; Yilma, D; Tesfaye, M; Girma, T; Christiansen, M; Hagen, C M; Wiesner, L; Castel, S; Aseffa, A; McIlleron, H; Pedersen, C; Friis, Henrik; Andersen, A B

    2015-01-01

    OBJECTIVES: Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma...

  13. Cytokine levels as biomarkers for leptospirosis patients.

    Science.gov (United States)

    Chirathaworn, C; Supputtamongkol, Y; Lertmaharit, S; Poovorawan, Y

    2016-09-01

    Inflammatory mediators were suggested to be biomarkers for prediction of disease severity. In this study, we investigated the levels of IL-6, IL-8, IL-10 and TNF-α in leptospirosis patients with mild or severe illnesses. Sera samples were divided into two groups. The OI group and NOI groups included sera from patients with and without organ involvement, respectively. Each group consisted of 20 pairs of sera. Twenty-five sera from healthy individuals were included as controls. Cytokine levels were compared. Although IL-6, IL-8 and IL-10 levels in acute sera from the OI group were significantly higher than NOI group, only IL-8 level was significantly higher in the OI group when cytokine levels in convalescent sera were compared. TNF-α, an inflammatory cytokine widely studied in leptospirosis was not significantly different between two groups of patients. Our data suggested that IL-6, IL-8 and IL-10 were involved in disease severity. However, time of specimen collection could affect the significant levels of cytokines especially as biomarkers for monitoring disease severity. PMID:27295614

  14. Involvement of cytokines in slow wave sleep

    OpenAIRE

    Krueger, James M.; Clinton, James M.; Winters, Bradley D.; Zielinski, Mark R.; Taishi, Ping; Jewett, Kathryn A.; Davis, Christopher J.

    2011-01-01

    Cytokines such as tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL1β) play a role in sleep regulation in health and disease. TNFα or IL1β injection enhances non-rapid eye movement sleep. Inhibition of TNFα or IL1β reduces spontaneous sleep. Mice lacking TNFα or IL1β receptors sleep less. In normal humans and in multiple disease states, plasma levels of TNFα covary with EEG slow wave activity (SWA) and sleep propensity. Many of the symptoms induced by sleep loss, for example, slee...

  15. Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Frøkiær, Hanne; Andersen, Anders D.; Lauritzen, Lotte

    2008-01-01

    , fibrinogen, C-reactive protein, interleukin-6, vascular cell adhesion molecule-1, P-selectin, oxidized LDL, cluster of differentiation antigen 40 ligand (CD40L), adiponectin, or fasting or postprandial BP or HR after adjustment for body weight changes. In conclusion, neither fish oil supplementation nor the...... intake in the S/B groups than in the R/K groups. Diet, (n-3) LCPUFA in peripheral blood mononuclear cells, blood pressure (BP), heart rate (HR), and plasma CVD risk markers were measured before and after the intervention. FO lowered fasting plasma triacylglycerol (TAG) (P <0.001) by 51% and 19% in the FO......+R/K-group and FO+S/B-group, respectively, which was also reflected in postprandial TAG measured after the intervention (P <0.01). Although a fat x FO interaction was found for monocyte chemoattractant protein-1, neither the FO nor fat intervention affected fasting plasma cholesterol, glucose, insulin...

  16. Effects of stressors and immune activating agents on peripheral and central cytokines in mouse strains that differ in stressor responsivity.

    Science.gov (United States)

    Gibb, Julie; Hayley, Shawn; Poulter, Michael O; Anisman, Hymie

    2011-03-01

    The impact of inflammatory immune activation on behavioral and physiological processes varies with antecedent stressor experiences. We assessed whether immune activation would differentially influence such outcomes as a function of stressor reactivity related to genetic differences. To this end, we assessed the influence of a social stressor (exposure to a dominant mouse) in combination with an acute immune challenge on behavior and on peripheral and central cytokines in stressor-reactive BALB/cByJ mice and the less reactive C57BL/6ByJ strain. As C57BL/6ByJ and BALB/cByJ mice are highly T helper type-1 (Th1) and Th2 responsive, respectively, the stressor effects were assessed in response to different challenges, namely the viral analogue poly I:C and the bacterial endotoxin lipopolysaccharide (LPS). The stressor enhanced the effects of LPS on sickness behaviors and plasma corticosterone particularly in BALB/cByJ mice, whereas the effects of poly I:C, which primarily affects Th1 processes, were not augmented by the stressor. As well, the stressor increased circulating cytokines in LPS treated C57BL/6ByJ mice, whereas the effects of poly I:C were diminished. Finally, like circulating cytokines, mRNA expression of pro-inflammatory cytokines within the prefrontal cortex and hippocampus varied with the mouse strain and with the stressor experience, and with the specific cytokine considered. Together, the experiments indicated that the impact of stressors vary with the nature of the immune challenge to which animals had been exposed. Moreover, given the diversity of the stressor effects on central and peripheral processes, it seems likely that the cytokine changes, HPA activity and sickness operate through independent mechanisms. PMID:21093579

  17. Cytokine Factors Present in Dengue Patient Sera Induces Alterations of Junctional Proteins in Human Endothelial Cells

    OpenAIRE

    Appanna, Ramapraba; Wang, Seok Mui; Ponnampalavanar, Sasheela A.; Lum, Lucy Chai See; Sekaran, Shamala Devi

    2012-01-01

    Plasma leakage in severe dengue has been postulated to be associated with skewed cytokine immune responses. In this study, the association of cytokines with vascular permeability in dengue patients was investigated. Human serum samples collected from 48 persons (13 with dengue fever, 29 with dengue hemorrhagic fever, and 6 healthy) were subjected to cytokines analysis by using Luminex Multiplex Technology. Selected serum samples from patients with dengue hemorrhagic fever sera and recombinant...

  18. Plasma membrane lipid–protein interactions affect signaling processes in sterol-biosynthesis mutants in Arabidopsis thaliana

    OpenAIRE

    Zauber, Henrik; Burgos, Asdrubal; Garapati, Prashanth; Schulze, Waltraud X.

    2014-01-01

    The plasma membrane is an important organelle providing structure, signaling and transport as major biological functions. Being composed of lipids and proteins with different physicochemical properties, the biological functions of membranes depend on specific protein-protein and protein-lipid interactions. Interactions of proteins with their specific sterol and lipid environment were shown to be important factors for protein recruitment into sub-compartmental structures of the plasma membrane...

  19. Cytokines and therapeutic oligonucleotides.

    Science.gov (United States)

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies. PMID:9740353

  20. The T1405N carbamoyl phosphate synthetase polymorphism does not affect plasma arginine concentrations in preterm infants.

    Directory of Open Access Journals (Sweden)

    Rob M J Moonen

    Full Text Available BACKGROUND: A C-to-A nucleotide transversion (T1405N in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1 has been associated with changes in plasma concentrations of L-arginine in term and near term infants but not in adults. In preterm infants homozygosity for the CPS1 Thr1405 variant (CC genotype was associated with an increased risk of having necrotizing enterocolitis (NEC. Plasma L-arginine concentrations are decreased in preterm infants with NEC. AIM: To examine the putative association between the CPS1 T1405N polymorphism and plasma arginine concentrations in preterm infants. METHODS: Prospective multicenter cohort study. Plasma and DNA samples were collected from 128 preterm infants (<30 weeks between 6 and 12 hours after birth. Plasma amino acid and CPS1 T1405N polymorphism analysis were performed. RESULTS: Distribution of genotypes did not differ between the preterm (CC:CA:AA = 55.5%:33.6%:10.9%, n = 128 and term infants (CC:CA:AA = 54.2%:35.4%:10.4%, n = 96. There was no association between the CPS1 genotype and plasma L-arginine or L-citrulline concentration, or the ornithine to citrulline ratio, which varies inversely with CPS1 activity. Also the levels of asymmetric dimethylarginine, and symmetric dimethylarginine were not significantly different among the three genotypes. CONCLUSIONS: The present study in preterm infants did not confirm the earlier reported association between CPS1 genotype and L-arginine levels in term infants.

  1. The Effect of Recombinant Erythropoietin on Plasma Brain Derived Neurotrophic Factor Levels in Patients with Affective Disorders: A Randomised Controlled Study

    OpenAIRE

    Maj Vinberg; Kamilla Miskowiak; Pernille Hoejman; Maria Pedersen; Lars Vedel Kessing

    2015-01-01

    The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (...

  2. Circulating levels of platelet α-granule cytokines in trauma patients

    DEFF Research Database (Denmark)

    Windeløv, Nis Agerlin; Ostrowski, Sisse Rye; Johansson, Per Ingemar;

    2015-01-01

    OBJECTIVE AND DESIGN: To elucidate whether platelets differentiate cytokine release following trauma, we prospectively measured three major platelet-derived cytokines in 213 trauma patients on hospital arrival. METHODS: We measured plasma levels of the anti-inflammatory β-thromboglobulins (β...

  3. Cytokines as potential biomarkers for Parkinson's disease: a multiplex approach.

    Science.gov (United States)

    Litteljohn, Darcy; Hayley, Shawn

    2012-01-01

    Cytokines, which are immunological messengers facilitating both intra- and inter-system communication, are considered central players in the neuroinflammatory cascades associated with the neurodegenerative process in Parkinson's disease (PD) and other neurological disorders. They have also been implicated in depression and other cognitive (e.g., memory impairment, dementia) and affective disturbances (e.g., anxiety) that show high co-morbidity with neurodegenerative diseases. As such, cytokines may hold great promise as serological biomarkers in PD, with potential applications ranging from early diagnosis and disease staging, to prognosis, drug discovery, and tracking the response to treatment. Subclassification or risk stratification in PD could be based (among other things) on reliably determined cytokine panel profiles or "signatures" of particular co-morbid disease states or at-risk groups (e.g., PD alone, PD with depression and/or dementia). Researchers and clinicians seeking to describe cytokine variations in health vs. disease will benefit greatly from technologies that allow a high degree of multiplexing and thus permit the simultaneous determination of a large roster of cytokines in single small-volume samples. The need for such highly paralleled assays is underscored by the fact that cytokines do not act in isolation but rather against a backdrop of complementary and antagonistic cytokine effects; ascribing valence to the actions of any one cytokine thus requires specific knowledge about the larger cytokine milieu. This chapter provides a technological overview of the major cytokine multiplex assay platforms before discussing the implications of such tools for biomarker discovery and related applications in PD and its depressive and cognitive co-morbidities. PMID:22933144

  4. Helminths and skewed cytokine profiles increase tuberculin skin test positivity in Warao Amerindians

    NARCIS (Netherlands)

    Verhagen, L.M.; Hermans, P.W.M.; Warris, A.; Groot, R. de; Maes, M.; Villalba, J.A.; del Nogal, B.; Hof, S. van den; Mughini Gras, L.; Soolingen, D. van; Pinelli, E.; Waard, J.H. de

    2012-01-01

    The immune regulatory mechanisms involved in the acquisition of Mycobacterium tuberculosis infection in children are largely unknown. We investigated the influence of parasitic infections, malnutrition and plasma cytokine profiles on tuberculin skin test (TST) positivity in Warao Amerindians in Vene

  5. Proteomic analysis of plasma from cows affected with milk fever using two-dimensional differential in-gel electrophoresis and mass spectrometry.

    Science.gov (United States)

    Xia, C; Zhang, H Y; Wu, L; Xu, C; Zheng, J S; Yan, Y J; Yang, L J; Shu, S

    2012-10-01

    Milk fever is an important metabolic disorder of dairy cows after calving, and is characterized by hypocalcemia, tetany, lateral recumbency, and eventual coma. To date, there have been many reports about the pathogenesis and pathophysiology of milk fever, but the plasma protein profile in milk fever has not been reported. The aim of our study was to investigate novel pathophysiological changes in the plasma proteome of cows affected with milk fever. Plasma samples were collected from eight Holstein cows with milk fever (T), and eight control Holstein cows without milk fever (C), at an intensive Holstein dairy farm in Heilongjiang province, China. Samples were analyzed by fluorescence two-dimensional (2D) differential in-gel electrophoresis (DIGE), followed by in-gel digestion, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) for peptide mass fingerprinting of selected protein spots. Eight of the 23 differential protein spots in the plasma of T and C cows were isolated and identified by 2D-DIGE and MALDI-TOF-MS. The protein spots represented five unique proteins, and had significant alterations in spot volume as determined by DeCyder differential in-gel analysis (DIA) software. The upregulated proteins were identified as serpin peptidase inhibitor (angiotensin), which regulates blood pressure and maintains fluid and electrolyte homeostasis, and endopin 2B which is involved in neural regulation. The downregulated proteins were serum albumin, which acts as a transport protein, fibrinogen beta chain which is involved in blood coagulation, and IgG heavy-chain C-region (IgG-C(H)) which participates in the immune response. In conclusion, we were able to use proteomic technologies to identify several novel plasma proteins in cows affected with milk fever. These findings may reveal new pathophysiological changes that occur in cows with milk fever. PMID:22119234

  6. Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma

    Directory of Open Access Journals (Sweden)

    Horimasu Yasushi

    2011-05-01

    Full Text Available Abstract Background KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD. Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history. Methods The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201. The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28, were analyzed by immunohistochemistry and digital image analysis. Results The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6. Conclusions KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.

  7. A lignan complex isolated from flaxseed does not affect plasma lipid concentrations or antioxidant capacity in healthy postmenopausal women

    DEFF Research Database (Denmark)

    Hallund, Jesper; Ravn-Haren, Gitte; Bügel, S.;

    2006-01-01

    A lignan complex rich in the plant lignan secoisolariciresinol diglucoside (SDG) was isolated from flaxseed. SDG is metabolized by the colonic microflora to the mammalian lignans enterodiol (END) and enterolactone (ENL), and was hypothesized to reduce plasma lipid concentrations and improve...... antioxidant capacity, The aim of this study was to investigate the effects of a lignan complex, providing 500 mg/d of SDG, on serum concentration and urinary excretion of ENL, plasma lipids, serum lipoprotein oxidation resistance, and markers of antioxidant capacity. Healthy postmenopausal women (n=22...

  8. Does cold plasma affect breaking dormancy and seed germination? Study on seeds of Lamb's Quarters (Chenopodium album agg.)

    Czech Academy of Sciences Publication Activity Database

    Šerá, Božena; Šerý, M.; Straňák, V.; Špatenka, P.; Tichý, M.

    2009-01-01

    Roč. 11, č. 6 (2009), s. 750-754. ISSN 1009-0630 Institutional research plan: CEZ:AV0Z60870520 Keywords : chenopodium album * low-pressure discharge * plasma treatment Subject RIV: EF - Botanics Impact factor: 0.380, year: 2009

  9. Cytokines as a stressor: implications for depressive illness.

    Science.gov (United States)

    Anisman, Hymie; Hayley, Shawn; Turrin, Nicolas; Merali, Zul

    2002-12-01

    Stressful events have been implicated in the provocation of depressive illness. Inasmuch as immunological challenge, and particularly cytokine administration, engender neuroendocrine and central neurochemical changes reminiscent of those provoked by psychogenic stressors, it was suggested that immune activation may also contribute to affective illness. The present report provides a brief overview of the neurochemical sequelae of acute and repeated interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and IL-2 treatment, describes some of the synergisms associated with these treatments, as well as their potential interactions with psychogenic stressors. In addition, a discussion is provided concerning the fact that cytokines, like stressors, may have time-dependent proactive effects, so that re-exposure to the treatments provoke greatly augmented neurochemical changes (sensitization). Given that the effects of cytokines are evident within hypothalamic, as well as extrahypothalamic sites, including various limbic regions, it is suggested that cytokines may impact on emotional changes, including depression. PMID:12466035

  10. Does Cold Plasma Affect Breaking Dormancy and Seed Germination? A Study on Seeds of Lamb's Quarters (Chenopodium album agg.)

    International Nuclear Information System (INIS)

    Low-pressure discharge is applied for stimulation of germination of two seed lots of Lamb's Quarters (Chenopodium album agg.) with different starting germinations (17%, 8%) and in different stages of dormancy. Different exposition durations with cold plasma treatment were applied. The variable of the ratio cumulative germination was calculated. The Richards' equation was used for curve-fitting and simulation of the growth curves. Population parameters, namely Vi - viability, Me - time, Qu - dispersion, and Sk - skewness, counted from the curves described the germination rate well. Significant differences among Qu confirmed the erratic dormancy and gradual germination of Lamb's Quarters. No difference in the Me parameter was found between two tested seed lots, and no interspecies characteristics were changed using low-pressure discharge. The results suggested that plasma treatment changed seed germination in Lamb's Quarters seeds.

  11. Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes?

    DEFF Research Database (Denmark)

    Staehr, P; Højlund, Kurt; Hother-Nielsen, O;

    2003-01-01

    turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF). RESULTS: Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10...... from basal rates of Rd, assessment of glucose turnover rates in euglycaemic clamp studies of Type 2 diabetic patients is not dependent on the method by which plasma glucose levels are lowered........7 +/- 2.9 mmol/l in the + ON and - ON studies, respectively, and were clamped at -5.5 mmol/l. Basal rates of glucose production (GP) were similar in the + ON and - ON studies, 83 +/- 13 vs. 85 +/- 14 mg m-2 min-1 (NS), whereas basal rates of glucose disappearance (Rd) were lower in the + ON than in the...

  12. Does Cold Plasma Affect Breaking Dormancy and Seed Germination? A Study on Seeds of Lamb's Quarters (Chenopodium album agg.)

    Science.gov (United States)

    Božena, Šerá; Michal, Šerý; Vitězslav, Štrañák; Petr, Špatenka; Milan, tichý

    2009-12-01

    Low-pressure discharge is applied for stimulation of germination of two seed lots of Lamb's Quarters (Chenopodium album agg.) with different starting germinations (17%, 8%) and in different stages of dormancy. Different exposition durations with cold plasma treatment were applied. The variable of the ratio cumulative germination was calculated. The Richards' equation was used for curve-fitting and simulation of the growth curves. Population parameters, namely Vi - viability, Me - time, Qu - dispersion, and Sk - skewness, counted from the curves described the germination rate well. Significant differences among Qu confirmed the erratic dormancy and gradual germination of Lamb's Quarters. No difference in the Me parameter was found between two tested seed lots, and no interspecies characteristics were changed using low-pressure discharge. The results suggested that plasma treatment changed seed germination in Lamb's Quarters seeds.

  13. Interleukin-10 and related cytokines and receptors.

    Science.gov (United States)

    Pestka, Sidney; Krause, Christopher D; Sarkar, Devanand; Walter, Mark R; Shi, Yufang; Fisher, Paul B

    2004-01-01

    The Class 2 alpha-helical cytokines consist of interleukin-10 (IL-10), IL-19, IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -epsilon, -kappa, -omega, -delta, -tau, and -gamma) and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29). The interaction of these cytokines with their specific receptor molecules initiates a broad and varied array of signals that induce cellular antiviral states, modulate inflammatory responses, inhibit or stimulate cell growth, produce or inhibit apoptosis, and affect many immune mechanisms. The information derived from crystal structures and molecular evolution has led to progress in the analysis of the molecular mechanisms initiating their biological activities. These cytokines have significant roles in a variety of pathophysiological processes as well as in regulation of the immune system. Further investigation of these critical intercellular signaling molecules will provide important information to enable these proteins to be used more extensively in therapy for a variety of diseases. PMID:15032600

  14. Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma

    OpenAIRE

    Horimasu Yasushi; Rönty Mikko; Vuopala Katri; Toljamo Tuula; Mazur Witold; Ishikawa Nobuhisa; Kohno Nobuoki; Kinnula Vuokko L

    2011-01-01

    Abstract Background KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD). Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history. Methods The concentrations of KL-6 in plas...

  15. Cytokine production capacity in depression and anxiety.

    Science.gov (United States)

    Vogelzangs, N; de Jonge, P; Smit, J H; Bahn, S; Penninx, B W

    2016-01-01

    Recent studies have suggested that immune function may be dysregulated in persons with depressive and anxiety disorders. Few studies examined the expression of cytokines in response to ex vivo stimulation of blood by lipopolysaccharide (LPS) to study the innate production capacity of cytokines in depression and anxiety. To investigate this, baseline data from the Netherlands Study of Depression and Anxiety (NESDA) were used, including persons (18-65 years; 66% women) with current (that is, past month; N=591) or remitted (N=354) DSM-IV depressive or anxiety disorders and healthy controls (N=297). Depressive and anxiety symptoms were measured by means of the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI). Using Multi-Analyte Profiling technology, plasma levels of 13 cytokines were assayed after whole blood stimulation by addition of LPS. Basal plasma levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α were also available. A basal and a LPS summary index were created. Results show that LPS-stimulated inflammation was associated with increased odds of current depressive/anxiety disorders (odds ratio (OR)=1.28, P=0.009), as was the case for basal inflammation (OR=1.28, P=0.001). These associations were no longer significant after adjustment for lifestyle and health (OR=1.13, P=0.21; OR=1.07, P=0.45, respectively). After adjustment for lifestyle and health, interleukin-8 was associated with both remitted (OR=1.25, P=0.02) and current (OR=1.28, P=0.005) disorders. In addition, LPS-stimulated inflammation was associated with more severe depressive (β=0.129, PIDS: interleukin (IL)-8, MCP-1, MMP2; BAI: LPS index, IL-6, IL-8, IL-10, IL-18, MCP-1, MMP2, TNF-β). To conclude, lifestyle and health factors may partly explain higher levels of basal, as well as LPS-stimulated inflammation in persons with depressive and anxiety disorders. However, production capacity of several cytokines was positively associated with severity

  16. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

    Paulsen, Gøran; Mikkelsen, Ulla Ramer; Raastad, Truls;

    2012-01-01

    -damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role of the...... variation in individual responses to a given exercise should, however be expected. The link between cytokine and satellite cell responses and exercise-induced muscle damage is not so clear The systemic cytokine response may be linked more closely to the metabolic demands of exercise rather than muscle...... damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to regeneration, whereas the biological significance of satellite cell proliferation after mild damage or non-damaging exercise remains...

  17. Vasculogenic Cytokines in Wound Healing

    Directory of Open Access Journals (Sweden)

    Victor W. Wong

    2013-01-01

    Full Text Available Chronic wounds represent a growing healthcare burden that particularly afflicts aged, diabetic, vasculopathic, and obese patients. Studies have shown that nonhealing wounds are characterized by dysregulated cytokine networks that impair blood vessel formation. Two distinct forms of neovascularization have been described: vasculogenesis (driven by bone-marrow-derived circulating endothelial progenitor cells and angiogenesis (local endothelial cell sprouting from existing vasculature. Researchers have traditionally focused on angiogenesis but defects in vasculogenesis are increasingly recognized to impact diseases including wound healing. A more comprehensive understanding of vasculogenic cytokine networks may facilitate the development of novel strategies to treat recalcitrant wounds. Further, the clinical success of endothelial progenitor cell-based therapies will depend not only on the delivery of the cells themselves but also on the appropriate cytokine milieu to promote tissue regeneration. This paper will highlight major cytokines involved in vasculogenesis within the context of cutaneous wound healing.

  18. Plasma TNF-α levels are higher in early pregnancy in patients with secondary compared with primary recurrent miscarriage

    DEFF Research Database (Denmark)

    Piosik, Zofia Maria; Goegebeur, Yuri; Klitkou, Louise;

    2013-01-01

    Specific pro-inflammatory cytokine profiles in plasma may characterize women with recurrent miscarriage (RM) but the dynamics of the cytokine profiles with progressing pregnancy is largely unknown.......Specific pro-inflammatory cytokine profiles in plasma may characterize women with recurrent miscarriage (RM) but the dynamics of the cytokine profiles with progressing pregnancy is largely unknown....

  19. Th2 cytokines inhibit lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Ira L Savetsky

    Full Text Available Lymphangiogenesis is the process by which new lymphatic vessels grow in response to pathologic stimuli such as wound healing, inflammation, and tumor metastasis. It is well-recognized that growth factors and cytokines regulate lymphangiogenesis by promoting or inhibiting lymphatic endothelial cell (LEC proliferation, migration and differentiation. Our group has shown that the expression of T-helper 2 (Th2 cytokines is markedly increased in lymphedema, and that these cytokines inhibit lymphatic function by increasing fibrosis and promoting changes in the extracellular matrix. However, while the evidence supporting a role for T cells and Th2 cytokines as negative regulators of lymphatic function is clear, the direct effects of Th2 cytokines on isolated LECs remains poorly understood. Using in vitro and in vivo studies, we show that physiologic doses of interleukin-4 (IL-4 and interleukin-13 (IL-13 have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration, and tubule formation. Inhibition of these cytokines with targeted monoclonal antibodies in the cornea suture model specifically increases inflammatory lymphangiogenesis without concomitant changes in angiogenesis. These findings suggest that manipulation of anti-lymphangiogenic pathways may represent a novel and potent means of improving lymphangiogenesis.

  20. Radiolabelled cytokines for imaging chronic inflammation

    International Nuclear Information System (INIS)

    Diagnosis and particularly follow-up of chronic inflammatory disorders could be often difficult in clinical practice. Indeed, traditional radiological techniques reveal only structural tissue alterations and are not able to monitor functional changes occurring in tissues affected by chronic inflammation. The continuous advances in the knowledge of the pathophysiology of chronic disorders, combine with the progress of radiochemistry, led to the development of new specific radiolabelled agents for the imaging of chronic diseases. In this scenario, cytokines, due to their pivotal role in such diseases, represent good candidate as radiopharmaceuticals. (author)

  1. Radiolabelled cytokines for imaging chronic inflammation

    Directory of Open Access Journals (Sweden)

    Signore Alberto

    2002-01-01

    Full Text Available Diagnosis and particularly follow-up of chronic inflammatory disorders could be often difficult in clinical practice. Indeed, traditional radiological techniques reveal only structural tissue alterations and are not able to monitor functional changes occurring in tissues affected by chronic inflammation. The continuous advances in the knowledge of the pathophysioloy of chronic disorders, combined with the progress of radiochemistry, led to the development of new specific radiolabelled agents for the imaging of chronic diseases. In this scenario, cytokines, due to their pivotal role in such diseases, represent good candidates as radiopharmaceuticals.

  2. Severity and timing: How prenatal stress exposure affects glial developmental, emotional behavioural and plasma neurosteroid responses in guinea pig offspring.

    Science.gov (United States)

    Bennett, Greer A; Palliser, Hannah K; Walker, David; Hirst, Jonathan

    2016-08-01

    Prenatal stress has been associated with a variety of developmental changes in offspring, notably those associated with brain development and subsequent risk for neuropathologies later in life. Recently, the importance of the timing and the severity of the stressor during pregnancy has been emphasized with neurosteroids including allopregnanolone implicated in the regulation of stress and also for endogenous neuroprotection in offspring. Prenatal stress was induced using strobe light exposure in pregnant guinea pigs (term 71days) in three defined stress exposure groups (Gestational Age (GA)35-65, GA50-65 and GA60-65). Stress was induced for 2h (9-11am) every 5days via strobe light exposure. A fetal cohort were euthanased at term with fetal brains and plasma collected. Anxiety-like behaviour was evaluated at 18 days of age in a separate cohort of offspring with brains and plasma collected at 21days of age. Markers for mature oligodendrocytes and reactive astrocytes were measured in the CA1 region of the hippocampus and the subcortical white matter. The neurosteroid allopregnanolone was measured by radioimmunoassay in offspring plasma. In the CA1 region of the hippocampus, fetuses from all stress groups showed reduced expression of mature oligodendrocytes and reactive astrocytes. By juvenility, all male stress exposure groups had recovered to levels of unaffected controls with the exception of the GA35-65 stress group. In juvenile females, mature oligodendrocyte marker expression was reduced in all stress groups and reactive astrocyte expression was reduced in the GA35-65 and GA60-65 stress groups by juvenility. Increased reactive astrocyte expression was also apparent in the subcortical white matter in both sexes both at term and at juvenility. Prenatally stressed offspring spent less time exploring in the object exploration test and also entered the inner zone of the open field less than controls at 18days of age. Circulating allopregnanolone concentrations were

  3. Different environmental temperatures affect amino acid metabolism in the eurytherm teleost Senegalese sole (Solea senegalensis Kaup, 1858) as indicated by changes in plasma metabolites.

    Science.gov (United States)

    Costas, Benjamín; Aragão, Cláudia; Ruiz-Jarabo, Ignacio; Vargas-Chacoff, Luis; Arjona, Francisco J; Mancera, Juan M; Dinis, Maria T; Conceição, Luís E C

    2012-07-01

    Senegalese sole (Solea senegalensis) is a eurytherm teleost that under natural conditions can be exposed to annual water temperature fluctuations between 12 and 26°C. This study assessed the effects of temperature on sole metabolic status, in particular in what concerns plasma free amino acid changes during thermal acclimation. Senegalese sole maintained at 18°C were acclimated to either cold (12°C) or warm (26°C) environmental temperatures for 21 days. Fish maintained at 18°C served as control. Plasma concentrations of cortisol, glucose, lactate, triglycerides, proteins, and free amino acids were assessed. Cold acclimation influenced interrenal responses of sole by increasing cortisol release. Moreover, plasma glucose and lactate concentrations increased linearly with temperature, presumably reflecting a higher metabolic activity of sole acclimated to 26°C. Acclimation temperature affected more drastically plasma concentrations of dispensable than that of indispensable amino acids, and different acclimation temperatures induced different responses. Asparagine, glutamine and ornithine seem to be of particular importance for ammonia detoxification mechanisms, synthesis of triglycerides that may be used during homeoviscous adaptation and, to a lesser extent, as energetic substrates in specimens acclimated to 12°C. When sole is acclimated to 26°C taurine, glutamate, GABA and glycine increased, which may suggest important roles as antioxidant defences, in osmoregulatory processes and/or for energetic purposes at this thermal regimen. In conclusion, acclimation to different environmental temperatures induces several metabolic changes in Senegalese sole, suggesting that amino acids may be important for thermal acclimation. PMID:21947601

  4. Variation of the Concentration of Isotopes Copper and Zinc in Human Plasmas of Patients Affected by Cancer

    Science.gov (United States)

    Triassi, Antonio

    2006-02-01

    In this paper, we demonstrate that the increase of copper and the reduction of zinc in the human plasma of patient with cancer, and in particular the Lymphoid Leukaemia, is a consequence of the isotopic constant of the enzymatic components copper/zinc dependent (DNA/RNA polymerase). Our hypothesis is that the reaction happens at the nuclear level in the human cell, and it is due to the action of a neutron (probably of deuterium of water) (J.F. Thomson, Biological Effects of Deuterium, Pergamon Press, Oxford, 1963) with the isotopic component of 64Zn transmutation into 65Cu stable following reaction: [ ^{64}Zn + N(HDO) rightarrow ^{65}Zn rightarrow beta^+ rightarrow EC rightarrow gamma rightarrow ^{65}Cu ] this produces energy of 0.325 MeV for the β+ and equal energy of 1.118 MeV for the photon γ with a half-life of 250 days.

  5. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices.

    Science.gov (United States)

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Rietveld, Trinet; van Miert, Joram N I; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-05-01

    The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P < 0.01; SA r = 0.69, P < 0.01), S I (Cau r = -0.51, P < 0.01; SA r = -0.41, P < 0.01), Φ dynamic (Cau r = -0.41, P < 0.01; SA r = -0.57, P < 0.01), and Φ oral (Cau r = -0.61, P < 0.01; SA r = -0.73, P < 0.01). Urinary C-peptide corresponded well to plasma C-peptide AUC (Cau r = 0.45, P < 0.01; SA r = 0.33, P < 0.05) and OMM estimate of renal C-peptide secretion (r = 0.42, P < 0.01). In general, glucose excretion plasma threshold for the presence of glucose in urine was ~10-10.5 mmol L(-1) in non-T2D individuals, but not measurable in T2D individuals. Renal glucose secretion during OGTT did not influence OMM indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose

  6. Cytokine profile in murine toxoplasmosis

    Institute of Scientific and Technical Information of China (English)

    Funda Dogruman-Al; Isil Fidan; Bekir Celebi; Emine Yesilyurt; Berna Erdal; Cahit Babur; Semra Kustimur

    2011-01-01

    Objective: To investigate which cytokines are produced after acute infection of mice withToxoplasma gondii (T. Gondii) RH strain. Methods: Mus domesticus domesticus mice in infected group were inoculated with with highly virulent T. Gondii RH strain by intraperitoneally. Serum samples were obtained from infected and non-infected mice for cytokine levels for ELISA assay. Results: The concentrations of tumor necrosis factor-α, interferonγ, interleukin (IL)-10 and IL-12 in the cardiac blood sample of the infected mice were significantly higher than those in uninfected controls (P0.05). Conclusions: According to our findings, immune response into T helper type 1 was predominant during acute T. gondii infection. Further characterization and purification of Toxoplasma molecule(s) implicated in the regulation of cytokines could lead to the development of new drug prospects to control Toxoplasma infection.

  7. Intracellular cytokine production and cognition in healthy older adults.

    Science.gov (United States)

    Simpson, Ellen E A; Hodkinson, Claire F; Maylor, Elizabeth A; McCormack, Jacqueline M; Rae, Gordon; Strain, Sean; Alexander, H Denis; Wallace, Julie M W

    2013-10-01

    Elevated concentrations of the pro-inflammatory cytokines IL-1β and IL-6 have been associated with impaired cognitive performance. There are, however, few studies that have examined the relationship between cytokine production and specific aspects of cognition in healthy older individuals. Two-colour flow cytometry was used to determine intracellular cytokine production by activated monocytes, and neuropsychological tests were performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in 93 apparently healthy men and women aged 55-70 years. A series of hierarchical regression analyses was carried out to examine the contribution of IL-1β and IL-6 (% expression and production (antibody binding capacity (ABC))) to recognition, attention and working memory, after controlling for socio-demographic variables (age, sex and social class). IL-1β% expression and IL-6 production predicted aspects of working memory. Recognition memory was found to be sensitive to the affects of age and social class. The current study suggests that higher intracellular cytokine production by activated monocytes may be predictive of lower cognitive performance in working memory in healthy older individuals. These findings indicate that utilization of models for in vivo cytokine production upon immune challenge may be useful in studying specific aspects of memory affected during inflammatory responses, for example in individuals at risk for cognitive decline owing to age-related inflammatory disorders. PMID:23664267

  8. Cytokines, STATs and Liver Disease

    Institute of Scientific and Technical Information of China (English)

    Bin Gao

    2005-01-01

    The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases. Cellular & Molecular Immunology.2005;2(2):92-100.

  9. Cytokines, STATs and Liver Disease

    Institute of Scientific and Technical Information of China (English)

    BinGao

    2005-01-01

    The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases. Cellular & Molecular Immunology. 2005;2(2):92-100.

  10. The concentration of plasma metabolites varies throughout reproduction and affects offspring number in wild brown trout (Salmo trutta).

    Science.gov (United States)

    Gauthey, Zoé; Freychet, Marine; Manicki, Aurélie; Herman, Alexandre; Lepais, Olivier; Panserat, Stéphane; Elosegi, Arturo; Tentelier, Cédric; Labonne, Jacques

    2015-06-01

    In wild populations, measuring energy invested in the reproduction and disentangling investment in gametes versus investment in reproductive behavior (such as intrasexual competition or intersexual preference) remain challenging. In this study, we investigated the energy expenditure in brown trout reproductive behavior by using two proxies: variation in weight and variation of plasma metabolites involved in energy production, over the course of reproductive season in a semi natural experimental river. We estimated overall reproductive success using genetic assignment at the end of the reproductive season. Results show that triglycerides and free fatty acid concentrations vary negatively during reproduction, while amino-acids and glucose concentrations remain stable. Decrease in triglyceride and free fatty acid concentrations during reproduction is not related to initial concentration levels or to weight variation. Both metabolite concentration variations and weight variations are correlated to the number of offspring produced, which could indicate that gametic and behavioral reproductive investments substantially contribute to reproductive success in wild brown trout. This study opens a path to further investigate variations in reproductive investment in wild populations. PMID:25666363

  11. Impact of exogenous gonadotropin stimulation on circulatory and follicular fluid cytokine profiles.

    Science.gov (United States)

    Baskind, N Ellissa; Orsi, Nicolas M; Sharma, Vinay

    2014-01-01

    Background. The natural cycle is the prototype to which we aspire to emulate in assisted reproduction techniques. Increasing evidence is emerging that controlled ovarian hyperstimulation (COH) with exogenous gonadotropins may be detrimental to oogenesis, embryo quality, and endometrial receptivity. This research aimed at assessing the impact of COH on the intrafollicular milieu by comparing follicular fluid (FF) cytokine profiles during stimulated in vitro fertilization (IVF) and modified natural cycle (MNC) IVF. Methods. Ten women undergoing COH IVF and 10 matched women undergoing MNC IVF were recruited for this pilot study. 40 FF cytokine concentrations from individual follicles and plasma were measured by fluid-phase multiplex immunoassay. Demographic/cycle/cytokine data were compared and correlations between cytokines were computed. Results. No significant differences were found between COH and MNC groups for patient and cycle demographics, including outcome. Overall mean FF cytokine levels were higher in the MNC group for 29/40 cytokines, significantly so for leukaemia inhibitory factor and stromal cell-derived factor-1α. Furthermore, FF MNC cytokine correlations were significantly stronger than for COH data. Conclusions. These findings suggest that COH perturbs intrafollicular cytokine networks, in terms of both cytokine levels and their interrelationships. This may impact oocyte maturation/fertilization and embryo developmental competence. PMID:25763393

  12. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: a randomised controlled study.

    Directory of Open Access Journals (Sweden)

    Maj Vinberg

    Full Text Available The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO on plasma brain derived neurotrophic factor (BDNF levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD (Hamilton Depression Rating Scale-17 items (HDRS-17 score >17 (study 1 and 43 patients with bipolar disorder (BD in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS ≤ 14 (study 2. In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU or saline (0.9% NaCl infusions in a double-blind, placebo-controlled, parallel--group design. Plasma BDNF levels were measured at baseline and at weeks 5, 9 and at follow up, week 14. In contrast with our hypothesis, EPO down regulated plasma BDNF levels in patients with TRD (mean reduction at week 9 (95% CI: EPO 10.94 ng/l (4.51-21.41 ng/l; mean increase at week 9: Saline 0.52 ng/l, p=0.04 (-5.88-4.48 ng/l p=0.04, partial ŋ2=0.12. No significant effects were found on BDNF levels in partially remitted patients with BD (p=0.35. The present effects of EPO on BDNF levels in patients with TRD point to a role of neurotrophic factors in the potential effects of EPO seen in TRD and BD. The neurobiological mechanisms underlying these effects and the interaction between EPO and peripheral levels on BDNF need to be further elucidated in human studies including a broad range of biomarkers.ClinicalTrials.gov: NCT00916552.

  13. Vasculogenic Cytokines in Wound Healing

    OpenAIRE

    Wong, Victor W.; Crawford, Jeffrey D.

    2013-01-01

    Chronic wounds represent a growing healthcare burden that particularly afflicts aged, diabetic, vasculopathic, and obese patients. Studies have shown that nonhealing wounds are characterized by dysregulated cytokine networks that impair blood vessel formation. Two distinct forms of neovascularization have been described: vasculogenesis (driven by bone-marrow-derived circulating endothelial progenitor cells) and angiogenesis (local endothelial cell sprouting from existing vasculature). Researc...

  14. Anesthesiology and the cytokine network

    Directory of Open Access Journals (Sweden)

    Barbara Lisowska

    2013-08-01

    Full Text Available The immune response is a highly specific reaction carried out by means of specialized cells that belong to the immune system. There are two types of immune response mechanisms aimed towards pathogens: non-specific, innate reactions, and specific, acquired reactions. Acquired immunity, characterized by its specificity, is comprised of lymphocytes, including both T cell and B cell populations. The role of B lymphocytes is not limited to the humoral response, though the cellular immune response is carried out mainly by various T lymphocyte subpopulations. The reactions of the humoral and cellular responses complement and stimulate one another mutually – cytokines are their common linking element. The attachment of cytokines to their specific receptors activates a sequence of signals – either intracellular or between the cells of various systems. This organization of respective connections and reactions, including the functional relations between cells of the immune response, in its complexity, is best described as a cytokine network. The response of the immune system to surgical trauma can be looked at from both a local and a general perspective. Not only surgical trauma caused by tissue damage, however, influences the functioning of the immune system, but also the drugs and techniques used during anesthesia. Our article is a presentation of the effects of medications used in anesthesia with respect to their influence on the cytokine network.

  15. Cytokine responses during chronic denervation

    Directory of Open Access Journals (Sweden)

    Olsson Tomas

    2005-11-01

    Full Text Available Abstract Background The aim of the present study was to examine inflammatory responses during Wallerian degeneration in rat peripheral nerve when the regrowth of axons was prevented by suturing. Methods Transected rat sciatic nerve was sutured and ligated to prevent reinnervation. The samples were collected from the left sciatic nerve distally and proximally from the point of transection. The endoneurium was separated from the surrounding epi- and perineurium to examine the expression of cytokines in both of these compartments. Macrophage invasion into endoneurium was investigated and Schwann cell proliferation was followed as well as the expression of cytokines IL-1β, IL-10, IFN-γ and TNF-α mRNA. The samples were collected from 1 day up to 5 weeks after the primary operation. Results At days 1 to 3 after injury in the epi-/perineurium of the proximal and distal stump, a marked expression of the pro-inflammatory cytokines TNF-α and IL-1β and of the anti-inflammatory cytokine IL-10 was observed. Concurrently, numerous macrophages started to gather into the epineurium of both proximal and distal stumps. At day 7 the number of macrophages decreased in the perineurium and increased markedly in the endoneurium of both stumps. At this time point marked expression of TNF-α and IFN-γ mRNA was observed in the endo- and epi-/perineurium of the proximal stump. At day 14 a marked increase in the expression of IL-1β could be noted in the proximal stump epi-/perineurium and in the distal stump endoneurium. At that time point many macrophages were observed in the longitudinally sectioned epineurium of the proximal 2 area as well as in the cross-section slides from the distal stump. At day 35 TNF-α, IL-1β and IL-10 mRNA appeared abundantly in the proximal epi-/perineurium together with macrophages. Conclusion The present studies show that even during chronic denervation there is a cyclic expression pattern for the studied cytokines. Contrary to the

  16. Temporal Cytokine Profiles in Severely Burned Patients: A Comparison of Adults and Children

    OpenAIRE

    Finnerty, Celeste C.; Jeschke, Marc G.; Herndon, David N; Gamelli, Richard; Gibran, Nicole; Klein, Matthew; Silver, Geoff; Arnoldo, Brett; Remick, Daniel; Tompkins, Ronald G.

    2008-01-01

    A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structural changes of essential organs. The release of cytokines has been implicated in this hypermetabolic response. The severity of the hypermetabolic response following burn injury increases with age, as does the mortality rate. Due to the relationship between the hypermetabolic and inflammatory responses, we sought to compare the plasma cytokine profiles following a severe burn in adults and in chi...

  17. Cytokine antagonists and their potential therapeutic use

    OpenAIRE

    Debets, Reno; Savelkoul, Huub

    1994-01-01

    textabstractNew and exciting developments in the understanding of the interaction between cytokines and their receptors, and the clinical application of cytokine antagonists, were discussed at a recent meeting. Here, Reno Debets and Huub Savelkoul revisit this progress.

  18. Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

    DEFF Research Database (Denmark)

    Erbayraktar, Serhat; Grasso, Giovanni; Sfacteria, Alessandra;

    2003-01-01

    Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects other tissues, including those of the nervous system. Enthusiasm for recombinant human erythropoietin...

  19. Avian cytokines in health and disease

    Directory of Open Access Journals (Sweden)

    Wigley P

    2003-01-01

    Full Text Available Cytokines are proteins secreted by cells that play an important role in the activation and regulation of other cells and tissues during inflammation and immune responses. Although well described in several mammalian species, the role of cytokines and other related proteins is poorly understood in avian species. Recent advances in avian genetics and immunology have begun to allow the exploration of cytokines in health and disease. Cytokines may be classified in a number of ways, but may be conveniently arranged into four broad groups on the basis of their function. Proinflammatory cytokines such as interleukin-6 and interleukin-1beta play a role in mediating inflammation during disease or injury. Th1 cytokines, including interleukin-12 and interferon-gamma, are involved in the induction of cell-mediated immunity, whereas Th2 cytokines such as interleukin-4 are involved in the induction of humoral immunity. The final group Th3 or Tr cytokines play a role in regulation of immunity. The role of various cytokines in infectious and non-infectious diseases of chickens and turkeys is now being investigated. Although there are only a few reliable ELISAs or bioassays developed for avian cytokines, the use of molecular techniques, and in particular quantitative RT-PCR (Taqman has allowed investigation of cytokine responses in a number of diseases including salmonellosis, coccidiosis and autoimmune thyroiditis. In addition the use of recombinant cytokines as therapeutic agents or as vaccine adjuvants is now being explored.

  20. The Predicted Value of Threatened Miscarriages Outcome by Plasma Levels of Th1/Th2 Cytokines and β-HCG%血清Th1/Th2细胞因子联合β-HCG预测先兆流产结局的价值

    Institute of Scientific and Technical Information of China (English)

    胡万芹; 杨丽华; 苏莹; 冷天艳

    2012-01-01

    Objective To explore the predicted value of threatened miscarriages outcome by plasma levels of Thl/Th2 cytokines and β -HCG. Methods We retrospectively analysed the plasma levels of IL2, IL10 and β -HCG in 60 women with threatened miscarriages in our hospital from 2009.1-2011.12, including 30 women with continual pregnancy and 30 women with unsuccessful pregnancy. The relationship between the indexes and the threatened miscarriages outcome was analysed. Results IL2/IL10 was significantly higher in unsuccessful pregnancy group than that in continual pregnancy group at the time that threatened miscarriages were diagnosed and the time that pregnancy outcome were clear (P 0.05). There was no significant difference in the level of P -HCG between the two groups when diagnosed (P>0.05). The level of β-HCG increased in continual pregnancy group and decreased in unsuccessful pregnancy group when the pregnancy outcome were clear (P <0.05). Conclusion There is no relationship between plasma IL2/IL10 and pregnancy weeks and embryo activity, increased IL2/IL10 means increased rate of unsuccessful pregnancy because of unbalanced maternal fetal immune function. It can be effectively predicted the threatened miscarriage outcome by combining plasma levels of Thl/Th2 cytokines and P -HCG, avoiding conservative management blindly.%目的 探讨血清Th1/Th2细胞因子联合β-HCG预测先兆流产结局的价值.方法 回顾分析2009年1月至2011年12月间昆明医科大学第二附属医院妇产科60例先兆流产孕妇血清IL2、IL10、β-HCG水平,继续妊娠者及妊娠失败者各30例,研究各指标与先兆流产结局的关系.结果 先兆流产诊断与妊娠结局明确当日,妊娠失败组IL2/IL10比值显著高于继续妊娠组(P<0.05),两组IL-2、IL-10和IL2/IL10水平在先兆流产诊断时与妊娠结局明确当日均无显著性变化(P>0.05);两组在先兆流产诊断时血β-HCG无差异(P>0.05),妊娠结局明确时妊娠失败组血HCG

  1. Secretion of immunoregulatory cytokines by mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Dobroslav; Kyurkchiev; Ivan; Bochev; Ekaterina; Ivanova-Todorova; Milena; Mourdjeva; Tsvetelina; Oreshkova; Kalina; Belemezova; Stanimir; Kyurkchiev

    2014-01-01

    According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.

  2. Discovery of potential new gene variants and inflammatory cytokine associations with fibromyalgia syndrome by whole exome sequencing.

    Directory of Open Access Journals (Sweden)

    Jinong Feng

    Full Text Available Fibromyalgia syndrome (FMS is a chronic musculoskeletal pain disorder affecting 2% to 5% of the general population. Both genetic and environmental factors may be involved. To ascertain in an unbiased manner which genes play a role in the disorder, we performed complete exome sequencing on a subset of FMS patients. Out of 150 nuclear families (trios DNA from 19 probands was subjected to complete exome sequencing. Since >80,000 SNPs were found per proband, the data were further filtered, including analysis of those with stop codons, a rare frequency (<2.5% in the 1000 Genomes database, and presence in at least 2/19 probands sequenced. Two nonsense mutations, W32X in C11orf40 and Q100X in ZNF77 among 150 FMS trios had a significantly elevated frequency of transmission to affected probands (p = 0.026 and p = 0.032, respectively and were present in a subset of 13% and 11% of FMS patients, respectively. Among 9 patients bearing more than one of the variants we have described, 4 had onset of symptoms between the ages of 10 and 18. The subset with the C11orf40 mutation had elevated plasma levels of the inflammatory cytokines, MCP-1 and IP-10, compared with unaffected controls or FMS patients with the wild-type allele. Similarly, patients with the ZNF77 mutation have elevated levels of the inflammatory cytokine, IL-12, compared with controls or patients with the wild type allele. Our results strongly implicate an inflammatory basis for FMS, as well as specific cytokine dysregulation, in at least 35% of our FMS cohort.

  3. Increasing levels of dietary crystalline methionine affect plasma methionine profiles, ammonia excretion, and the expression of genes related to the hepatic intermediary metabolism in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Rolland, Marine; Skov, Peter V; Larsen, Bodil K; Holm, Jørgen; Gómez-Requeni, Pedro; Dalsgaard, Johanne

    2016-08-01

    Strictly carnivorous fish with high requirements for dietary protein, such as rainbow trout (Oncorhynchus mykiss) are interesting models for studying the role of amino acids as key regulators of intermediary metabolism. Methionine is an essential amino acid for rainbow trout, and works as a signalling factor in different metabolic pathways. The study investigated the effect of increasing dietary methionine intake on the intermediary metabolism in the liver of juvenile rainbow trout. For this purpose, five diets were formulated with increasing methionine levels from 0.60 to 1.29% dry matter. The diets were fed in excess for six weeks before three sampling campaigns carried out successively to elucidate (i) the hepatic expression of selected genes involved in lipid, glucose and amino acid metabolism; (ii) the postprandial ammonia excretion; and (iii) the postprandial plasma methionine concentrations. The transcript levels of enzymes involved in lipid metabolism (fatty acid synthase, glucose 6 phosphate dehydrogenase and carnitine palmitoyl transferase 1 a), gluconeogenesis (fructose-1,6-biphosphatase) and amino acid catabolism (alanine amino transferase and glutamate dehydrogenase) were significantly affected by the increase in dietary methionine. Changes in gene expression reflected to some extent the decrease in ammonia excretion (P=0.022) and in the hepatosomatic index (HSI; Ptrout responded in a dose-dependent manner to increasing levels of dietary methionine. PMID:27105833

  4. Malaria: toxins, cytokines and disease

    DEFF Research Database (Denmark)

    Jakobsen, P H; Bate, C A; Taverne, J;

    1995-01-01

    In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while...... hypoglycaemia may be due to direct effects of similar molecules on glucose metabolism. These molecules appear to be phospholipids and we suggest that when fully characterized they might form the basis of antitoxic therapy for malaria....

  5. Clinical implication of perioperative inflammatory cytokine alteration.

    Science.gov (United States)

    Hsing, Chung-Hsi; Wang, Jhi-Joung

    2015-03-01

    Cytokines are key modulators of inflammatory responses, and play an important role in the defense and repair mechanisms following trauma. After traumatic injury, an immuno-inflammatory response is initiated immediately, and cytokines rapidly appear and function as a regulator of immunity. In pathologic conditions, imbalanced cytokines may provide systemic inflammatory responses or immunosuppression. Expression of perioperative cytokines vary by different intensities of surgical trauma and types of anesthesia and anesthetic agents. Inflammatory cytokines play important roles in postoperative organ dysfunction including central nervous system, cardiovascular, lung, liver, and kidney injury. Inhibition of cytokines could protect against traumatic injury in some circumstances, therefore cytokine inhibitors or antagonists might have the potential for reducing postoperative tissue/organ dysfunction. Cytokines are also involved in wound healing and post-traumatic pain. Application of cytokines for the improvement of surgical wound healing has been reported. Anesthesia-related immune response adjustment might reduce perioperative morbidity because it reduces proinflammatory cytokine expression; however, the overall effects of anesthetics on postoperative immune-inflammatory responses needs to be further investigated. PMID:25837846

  6. PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines.

    Directory of Open Access Journals (Sweden)

    Teruki Yanagi

    Full Text Available While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL. Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells.

  7. Proinflammatory cytokines, aging, and age-related diseases.

    Science.gov (United States)

    Michaud, Martin; Balardy, Laurent; Moulis, Guillaume; Gaudin, Clement; Peyrot, Caroline; Vellas, Bruno; Cesari, Matteo; Nourhashemi, Fati

    2013-12-01

    Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as "inflamm-aging." High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging. PMID:23792036

  8. Cytokines and Mycobacterium leprae induce apoptosis in human Schwann cells.

    Science.gov (United States)

    Oliveira, Rosane B; Sampaio, Elizabeth P; Aarestrup, Fernando; Teles, Rosane M B; Silva, Tatiana P; Oliveira, Ariane L; Antas, Paulo R Z; Sarno, Euzenir N

    2005-10-01

    The development of deformities during the course of leprosy disease is a major public health concern worldwide. It is possible that cytokine production and apoptosis of Schwann cells (SCs) directly affect nerve degeneration and regeneration leading to injury of the myelin sheath and axon. In the present study, the expression of TNFalpha, TGFbeta, and their receptors, in addition to cell death triggered by cytokines or whole Mycobacterium leprae were investigated in a human SC line. The results showed the presence of TNF-Rs and TGF-RII on the SC membrane and the shedding of TNF-Rs during the culture period. Evaluation of cell death was performed through TUNEL and flow cytometry techniques. TNFalpha/TGFbeta combination as well as M. leprae infection triggered an increase in the apoptosis rate in the cultured SC. Moreover, reverse transcriptase-polymerase chain reaction assay revealed that M. leprae upregulated the expression of such cytokines and their receptors on the SC line. Despite the detection of TNFalpha mRNA, no protein was found in the culture supernatants. The data indicate that induction of SC death after cell interaction with M. leprae may, in fact, be implicated in the pathogenesis of nerve damage, which can most likely be modulated by in vivo cytokine production. PMID:16215460

  9. FUNDAMENTAL IMMUNOBIOLOGY OF PRO-INFLAMMATORY CYTOKINES AND MIF

    Directory of Open Access Journals (Sweden)

    A. P. Suslov

    2014-07-01

    Full Text Available Fundamental immunobiology of proinflammatory cytokines and MIFThere are a lot of similarity as well as differences when we compare cytokines with MIF according their biological properties. MIF characteristics are unique structure, organs and tissues ubiquity, extremely wide variety of functions (proinflammatory cytokine, enzyme, hormone, ability to be induced by glucocorticoid hormones and affects as their immunosuppressive effects antagonist. MIF exists in preformed condition in lymphocytes, macrophages and endothelium cells. It secrets by these cells and operates as a mobilizing defense system factor in the first minutes of foreign invasion. MIF exhibits the properties of super-ligand binding with many biologically important molecules. This factor carries out the functions that are important for cell activation, proliferation and death, using a variety of intracellular signaling pathways. Some of MIF homologues exists in plants and bacteria earlier than innate and adaptive immune systems appears in evolution. In ontogenesis MIF appears at the stage of firsts cell divisions. MIF has a lot of functions, variety of ligand bindings, many effector pathways, it appears early in ontogeny and phylogeny. MIF takes part into protective reactions at any levels – from cell up to whole organism. All these MIF features taking together into account make it possible to possess it as a particular type of cytokine – eocytokine (from Greek word “eo” – early. It is assumed that MIF may function as some kind of cells and organisms "natural stability" key factor.

  10. Cytokine and anti-cytokine therapies for inflammatory bowel disease.

    Science.gov (United States)

    Ogata, Haruhiko; Hibi, Toshifumi

    2003-01-01

    Although the pathogenesis of inflammatory bowel disease (IBD) remains elusive, it appears that there is chronic activation of the immune and inflammatory cascade in genetically susceptible individuals. Current disease management guidelines have therefore focused on the use of anti-inflammatory agents, aminosalicylates and corticosteroids. These conventional therapies continue to be a first choice in the management of IBD. Immunomodulators, such as azathioprine, 6-mercaptopurine, methotrexate or cyclosporin, are demonstrating increasing importance against steroid-resistant and steroid-dependent patients. However, some patients are still refractory to these therapies. Recent advances in the understanding of the pathophysiological conditions of IBD have provided new immune system modulators as therapeutic tools. Other immunosuppressive agents including FK506 and thalidomide have expanded the choice of medical therapies available for certain subgroups of patients. Furthermore, biological therapies have begun to assume a prominent role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment have been reported with dramatic successes. However, observations in larger numbers of treated patients are needed to explicate fully the safety of or risks posed by this agent such as developing lymphoma, or other malignancies. Another anti-inflammatory cytokine-therapy includes anti anti-IL-6R, anti-IL-12 or toxin-conjugated anti IL-7R, recombinant cytokines (IL-10 or IL-11). Given the diversity of proinflammatory products under its control, NF-kappaB may be viewed as a master switch in lymphocytes and macrophages, regulating inflammation and immunity. Although some of them still need more confirmatory studies, those immune therapies will provide new insights into cell-based and gene-based treatment against IBD in near future. PMID:12769750

  11. CYTOKINE REGULATION OF ULCEROGENESIS IN GASTRODUODENAL MUCOSA

    Directory of Open Access Journals (Sweden)

    L. V. Matveeva

    2013-01-01

    Full Text Available Ulcerogenesis in gastroduodenal mucosa area is a complex multistep process. Its, phases arecontrolled by interaction and activation of pro­ and antiinflammatory cytokine cascade. Present review article summarizes scientific data on impact of cytokines upon ulcerative and reparatory processes, a variety of their diagnostic and therapeutic options is defined. Evaluation of cytokine status, or, in some cases, cytokine genotyping in patients with stomach and duodenal ulcers, may predict clinical course of the disease, as well as efficiency of basic and eradication therapy, correction of the treatment.

  12. Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity

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    Manfred Kunz

    2009-01-01

    Full Text Available The precise pathomechanisms of human autoimmune diseases are still poorly understood. However, a deepened understanding of these is urgently needed to improve disease prevention and early detection and guide more specific treatment approaches. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been detected. Major contributions were made by experiments using DNA microarray technology, which has been used for the analysis of gene expression patterns in chronic inflammatory and autoimmune diseases, among which were rheumatoid arthritis, systemic lupus erythematosus, psoriasis, systemic sclerosis, multiple sclerosis, and type-1 diabetes. In systemic lupus erythematosus, a so-called interferon signature has been identified. In psoriasis, researchers found a particular immune signalling cluster. Moreover the identification of a new subset of inflammatory T cells, so-called Th17 T cells, secreting interleukin (IL-17 as one of their major cytokines and the identification of the IL-23/IL-17 axis of inflammation regulation, have significantly improved our understanding of autoimmune diseases. Since a plethora of new treatment approaches using antibodies or small molecule inhibitors specifically targeting cytokines, cellular receptors, or signalling mechanisms has emerged in recent years, more individualized treatment for affected patients may be within reach in the future.

  13. Speciation of arsenic in human nail and hair from arsenic-affected area by HPLC-inductively coupled argon plasma mass spectrometry

    International Nuclear Information System (INIS)

    Nail and hair are rich in fibrous proteins, i.e., α-keratins that contain abundant cysteine residues (up to 22% in nail and 10-14% in hair). Although they are metabolically dead materials in the epidermis, the roots are highly influenced by the health status of the living beings and their analyses are used as a tool to monitor occupational and environmental exposure to toxic elements. The aims of the present study are to speciate arsenicals in human nail and hair and also to judge whether they should be used as a biomarker to arsenic (As) exposure and/or toxicity. All human fingernail and hair samples (n = 47) were collected from the As-affected area of West Bengal, India. Speciation of arsenicals in water extracts of fingernails and hair at 90 degree sign C was carried out by HPLC-inductively coupled argon plasma mass spectrometer (ICP MS). Fingernails contained iAsIII (58.6%), iAsV (21.5), MMAV (7.7), DMAIII (9.2), and DMAV (3.0), and hair contained iAsIII (60.9%), iAsV (33.2), MMAV (2.2), and DMAV (3.6). Fingernails contained DMAIII, but hair did not. The higher percentage of iAsIII both in fingernails and hair than that of iAsV suggests more affinity of iAsIII to keratin. Although all arsenicals in fingernails and hair correlate to As exposure positively, As speciation in fingernails seems to be more correlated with arsenism than that in hair. Exogenous contamination is a confounding factor for hair to consider it as a biomarker, whereas this is mostly absent in fingernails, which recommends it to be a better biomarker to arsenic exposure. DMAIII content in fingernails and DMAV contents in both fingernails and hair could be the biomarker to As exposure

  14. Mechanically loaded myotubes affect osteoclast formation

    NARCIS (Netherlands)

    P. Juffer; R.T. Jaspers; J. Klein-Nulend; A.D. Bakker

    2014-01-01

    In response to mechanical loading skeletal muscle produces numerous growth factors and cytokines that enter the circulation. We hypothesized that myotubes produce soluble factors that affect osteoclast formation and aimed to identify which osteoclastogenesis-modulating factors are differentially pro

  15. Infusion of hypertonic saline before elective hysterectomy: effects on cytokines and stress hormones

    DEFF Research Database (Denmark)

    Kølsen-Petersen, Jens Aage; Bendtzen, Klaus; Tønnesen, Else Kirstine

    2008-01-01

    BACKGROUND: Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery. METHODS: Sixty-two women undergoing abdominal hysterectomy were randomized in a...... double-blind study to infusion of NaCl 7.5% (HS), NaCl 0.9% (NS4), both 4 ml kg(-1), or NaCl 0.9% 32 ml kg(-1) (NS32) over 20 min. Blood was collected at baseline, 1, 4, and 24 h after surgery (n=34) for the determination of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, IL-1ra, and tumour necrosis...... factor-alpha. Serum cortisol and vasopressin were measured at these time points and 48 h after operation. Epinephrine and norepinephrine (n=26) were quantified at baseline, after infusion, 25 min after incision, 1, and 4 h after surgery. Finally, C-reactive protein was measured at baseline, 24, and 48 h...

  16. Interleukin-6, a mental cytokine.

    Science.gov (United States)

    Spooren, Anneleen; Kolmus, Krzysztof; Laureys, Guy; Clinckers, Ralph; De Keyser, Jacques; Haegeman, Guy; Gerlo, Sarah

    2011-06-24

    Almost a quarter of a century ago, interleukin-6 (IL-6) was discovered as an inflammatory cytokine involved in B cell differentiation. Today, IL-6 is recognized to be a highly versatile cytokine, with pleiotropic actions not only in immune cells, but also in other cell types, such as cells of the central nervous system (CNS). The first evidence implicating IL-6 in brain-related processes originated from its dysregulated expression in several neurological disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. In addition, IL-6 was shown to be involved in multiple physiological CNS processes such as neuron homeostasis, astrogliogenesis and neuronal differentiation. The molecular mechanisms underlying IL-6 functions in the brain have only recently started to emerge. In this review, an overview of the latest discoveries concerning the actions of IL-6 in the nervous system is provided. The central position of IL-6 in the neuroinflammatory reaction pattern, and more specifically, the role of IL-6 in specific neurodegenerative processes, which accompany Alzheimer's disease, multiple sclerosis and excitotoxicity, are discussed. It is evident that IL-6 has a dichotomic action in the CNS, displaying neurotrophic properties on the one hand, and detrimental actions on the other. This is in agreement with its central role in neuroinflammation, which evolved as a beneficial process, aimed at maintaining tissue homeostasis, but which can become malignant when exaggerated. In this perspective, it is not surprising that 'well-meant' actions of IL-6 are often causing harm instead of leading to recovery. PMID:21238488

  17. Ca2+- and Mg2+-ATPase activities in winter wheat root plasma membranes as affected by NaCl stress during growth

    NARCIS (Netherlands)

    Mansour, MMF; van Hasselt, PR; Kuiper, PJC

    1998-01-01

    Winter wheat seedlings were grown in Hoagland nutrient solution with or without 100 mmol/L NaCl added. Plasma membranes from root cells were prepared by aqueous polymer two phase partitioning and the stimulation of plasma membrane ATPase activity by Mg2+ and Ca2+ was investigated. The enzyme was act

  18. Vitamin K circulating cytokines and bone mineral density in older men and women

    Science.gov (United States)

    Background: Vitamin K has been shown in vitro to modulate cytokines involved in bone turnover, including interleukin-6 (IL-6) and osteoprotegerin (OPG). Objective: To assess: (1) associations between measures of vitamin K status [plasma phylloquinone and serum percent undercarboxylated osteocalcin (...

  19. An elevated pro-inflammatory cytokine profile in multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Dantoft, Thomas Meinertz; Elberling, J.; Pedersen, Susanne Brix;

    2014-01-01

    concentrations of 14 cytokines, chemokines and growth and allergen-specific IgE were measured. All participants completed a questionnaire including questions on MCS, psychological distress, morbidities and medication use at the time of the study. ResultsPlasma levels of interleukin-1β, -2, -4, and -6 were...

  20. Exposure to moderate air pollution during late pregnancy and cord blood cytokine secretion in healthy neonates.

    OpenAIRE

    Latzin, Philipp; Frey, Urs; Armann, Jakob; Kieninger, Elisabeth; Fuchs, Oliver; Röösli, Martin; Schaub, Bianca

    2011-01-01

    Background/Objectives Ambient air pollution can alter cytokine concentrations as shown in vitro and following short-term exposure to high air pollution levels in vivo. Exposure to pollution during late pregnancy has been shown to affect fetal lymphocytic immunophenotypes. However, effects of prenatal exposure to moderate levels of air pollutants on cytokine regulation in cord blood of healthy infants are unknown. Methods In a birth cohort of 265 healthy term-born neonates, we asses...

  1. Cortisol, Cytokines, and Hippocampal Volume in the Elderly

    Directory of Open Access Journals (Sweden)

    Keith Daniel Sudheimer

    2014-07-01

    Full Text Available Separate bodies of literature report that elevated pro-inflammatory cytokines and cortisol negatively affect hippocampal structure and cognitive functioning, particularly in older adults. Although interactions between cytokines and cortisol occur through a variety of known mechanisms, few studies consider how their interactions affect brain structure. In this preliminary study, we assess the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight community-dwelling older adults underwent blood draws for quantification of circulating cytokines and saliva collections to quantify the cortisol awakening response. Hippocampal volume measurements were made using structural magnetic resonance imaging. Elevated levels of waking cortisol in conjunction with higher concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF-alpha were also associated with smaller hippocampal volumes. These data provide preliminary evidence that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, are associated with smaller hippocampal volume in older adults. We suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis and inflammation processes may explain hippocampal volume reductions in older adults better than either set of measures do in isolation.

  2. Cytokines and organ failure in acute pancreatitis

    DEFF Research Database (Denmark)

    Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller;

    2012-01-01

    We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP).......We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP)....

  3. Cytokines and mood in healthy young adults

    NARCIS (Netherlands)

    Jansen, J.; Fernstrand, A.M.; Van De Loo, A.J.A.E.; Garssen, J.; Verster, J.C.

    2015-01-01

    Purpose: A link between chronic inflammation and neuropsychiatric disorders has been demonstrated previously. For example, pro- and anti-inflammatory cytokines have shown to impact neurocircuits relevant to mood regulation. Elevated levels of inflammatory cytokines have been associated with the deve

  4. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

    2006-01-01

    Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

  5. Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbAlc levels, but is not acutely affected by food intake

    DEFF Research Database (Denmark)

    Ryskjaer, Jakob; Deacon, Carolyn F.; Carr, Richard D;

    2006-01-01

    hormones are metabolized quickly by the enzyme dipeptidyl peptidase-IV (DPP-IV). It is well known that type-2 diabetic patients have an impaired incretin effect. Therefore, the aim of the present study was to investigate plasma DPP-IV activity in the fasting and the postprandial state in type-2 diabetic...... patients, DPP-IV activity was positively correlated to FPG and HbAlc and negatively to the duration of diabetes and age of the patients. No postprandial changes were seen in plasma DPP-IV activity in any of the groups. CONCLUSIONS: Plasma DPP-IVactivity increases in the fasting state and is positively...

  6. Increased levels of inflammatory cytokines and endothelin-1 in alveolar macrophages from patients with chronic heart failure.

    Directory of Open Access Journals (Sweden)

    Liv I Bjoner Sikkeland

    Full Text Available BACKGROUND: Pathophysiological interactions between heart and lungs in heart failure (HF are well recognized. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is also increased in alveolar macrophages in HF. METHODOLOGY/PRINCIPAL FINDINGS: Lung function, hemodynamic parameters, gene expression in alveolar macrophages, and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20 were compared to control subjects (n = 16. Our principal findings were: (1 Lung function was significantly lower in HF patients compared to controls (P<0.05. (2 mRNA levels of ET-1, tumor necrosis factor (TNF-α and interleukin-6 (IL-6 were increased in alveolar macrophages from HF patients. (3 Plasma levels of ET-1, TNFα, IL-6 and MCP-1 were significantly increased in HF patients, whereas our data indicate a net pulmonary release of MCP-1 into the circulation in HF. CONCLUSIONS/SIGNIFICANCE: Several important cytokines and ET-1 are induced in alveolar macrophages in human HF. Further studies should clarify whether increased synthesis of these factors affects pulmonary remodeling and, directly or indirectly, adversely affects the failing myocardium.

  7. Soluble cytokine receptors in biological therapy.

    Science.gov (United States)

    Fernandez-Botran, Rafael; Crespo, Fabian A; Sun, Xichun

    2002-08-01

    Due to their fundamental involvement in the pathogenesis of many diseases, cytokines constitute key targets for biotherapeutic approaches. The discovery that soluble forms of cytokine receptors are involved in the endogenous regulation of cytokine activity has prompted substantial interest in their potential application as immunotherapeutic agents. As such, soluble cytokine receptors have many advantages, including specificity, low immunogenicity and high affinity. Potential disadvantages, such as low avidity and short in vivo half-lifes, have been addressed by the use of genetically-designed receptors, hybrid proteins or chemical modifications. The ability of many soluble cytokine receptors to inhibit the binding and biological activity of their ligands makes them very specific cytokine antagonists. Several pharmaceutical companies have generated a number of therapeutic agents based on soluble cytokine receptors and many of them are undergoing clinical trials. The most advanced in terms of clinical development is etanercept (Enbrel, Immunex), a fusion protein between soluble TNF receptor Type II and the Fc region of human IgG1. This TNF-alpha; antagonist was the first soluble cytokine receptor to receive approval for use in humans. In general, most agents based on soluble cytokine receptors have been safe, well-tolerated and have shown only minor side effects in the majority of patients. Soluble cytokine receptors constitute a new generation of therapeutic agents with tremendous potential for applications in a wide variety of human diseases. Two current areas of research are the identification of their most promising applications and characterisation of their long-term effects. PMID:12171504

  8. The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied

    OpenAIRE

    Schilder, Louise; Nurmohamed, S Azam; ter Wee, Pieter M.; Paauw, Nanne J.; Girbes, Armand RJ; Beishuizen, Albertus; Beelen, Robert HJ; Groeneveld, AB Johan

    2014-01-01

    Introduction Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI), and levels reflect severity of disease in critically ill patients. However, continuous venovenous hemofiltration (CVVH) may affect plasma levels by clearance or release of NGAL by activated neutrophils in the filter, dependent on the anticoagulation regimen applied. We therefore studied handling of NGAL by CVVH in patients with AKI. Methods Immediately before initiation of CVVH, prefilt...

  9. A comparison of cytokine responses during prolonged cycling in normal and hot environmental conditions

    Directory of Open Access Journals (Sweden)

    Ludmila M Cosio-Lima

    2011-01-01

    Full Text Available Ludmila M Cosio-Lima, Bhargav V Desai, Petra B Schuler, Lesley Keck, Logan ScheelerDepartment of Health, Leisure, and Exercise Science, University of West Florida, Pensacola, FL, USAPurpose: Components of immune function are affected by physical activity in an adverse environment. The purpose of this study was to compare plasma differences in inflammatory cytokines including tumor necrosis factor α (TNF-α and interleukin 6 (IL-6, in addition to the stress hormone cortisol, during prolonged cycling under normal and hot environmental conditions in elite cyclists.Methods and design: Six trained elite male cyclists (27 ± 8 years; 75.5 ± 4 kg; maximum oxygen uptake [VO2max] = 66 ± 6 mL/kg/min, mean ± SD. The cyclists biked for 2.5 h at their prescribed 60% maximum exercise workload (Wmax or 75% VO2max either in an environmental chamber set at 15°C and 40% relative humidity (NEUTRAL or at 35°C and 40% relative humidity (HOT. The cyclists were given 4 mL of water/kg body weight every 15 min under both conditions.Results: Total cortisol concentrations were elevated (P < 0.05 immediately postexercise and 12 h postexercise in both the NEUTRAL and HOT conditions. TNF-α concentrations were only significantly (P = 0.045 elevated postexercise in HOT conditions. During the HOT conditions, a significant (P = 0.006 and 0.007, respectively difference in IL-6 was seen immediately after and 12 h postexercise. During the NEUTRAL condition, IL-6 was only significantly elevated postexercise (P < 0.05.Conclusions: Heat exposure during a long bout of exercise is sufficient to elicit stress response in elite cyclists. However, the degree of release of anti-inflammatory and proinflammatory cytokines might be related to several factors that include the athlete’s fitness level, hydration status, exercise intensity, and length of exposure to hot environments.Keywords: cytokines, inflammation, heat, exercise, performance 

  10. Dharmendra antigen but not integral M. leprae is an efficient inducer of immunostimulant cytokine production by human monocytes, and M. leprae lipids inhibit the cytokine production.

    Science.gov (United States)

    Nakamura, C; Fukutomi, Y; Kashiwabara, Y; Oomoto, Y; Kojima, M; Hayashi, H; Onozaki, K

    1997-03-01

    Killed integral Mycobacterium leprae, Mitsuda antigen, and chloroform-treated M. leprae, Dharmendra antigen (Dh-Ag), have been used for the classification of leprosy patients based on cell-mediated immunity. Heat-killed M. leprae also were used as a component of the Convit vaccine. Human blood monocytes were stimulated with M. leprae or Dh-Ag and their cytokine-inducing ability was compared. Monocytes were cultured in the presence of fresh human serum because of the efficiency of cytokine induction and the phagocytosis of M. leprae have been shown to be optimal in the presence of fresh serum. M. leprae and Dh-Ag were equally phagocytosed by monocytes. Dh-Ag was more potent than M. leprae in the induction of immunostimulatory/proinflammatory cytokines, interleukin-1 (IL-1), IL-6 and tumor necrosis factor (TNF). In contrast, a comparable level of IL-1ra, an immunosuppressive cytokine, was induced by M. leprae and Dh-Ag. The lipids extracted from M. leprae induced none of these cytokines by monocytes. Nevertheless, when monocytes were pretreated with the lipids followed by stimulation with Dh-Ag, productions of IL-1, IL-6 and TNF were all inhibited in a dose-dependent manner. However, the lipids did not inhibit the cytokine production induced by other stimuli including BCG and lipopolysaccharide. Moreover the lipids did not affect the production of IL-1ra. These results suggest that the lipids from M. leprae are responsible for the poor cytokine-inducing ability of M. leprae, thus favoring their infection. These results also suggest that Dh-Ag rather than integral M. leprae may be useful as a vaccine candidate because Dh-Ag is able to induce a large amount of cytokines from monocytes. PMID:9207755

  11. Cytokine profiling for prediction of symptomatic radiation-induced lung injury

    International Nuclear Information System (INIS)

    Purpose: To analyze plasma cytokine profiles before the initiation of radiation therapy to define a cytokine phenotype that correlates with risk of developing symptomatic radiation-induced lung injury (SRILI). Methods and Materials: Symptomatic radiation-induced lung injury was evaluated in 55 patients (22 with SRILI and 33 without SRILI), according to modified National Cancer Institute common toxicity criteria. These plasma samples were analyzed by the multiplex suspension bead array system (Bio-Rad Laboratories; Hercules, CA), which included the following cytokines: interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17, granulocyte/macrophage colony-stimulating factor, interferon-γ, monocyte chemotactic protein 1, macrophage inflammatory protein 1β, tumor necrosis factor α, and granulocyte colony-stimulating factor. Results: Significant differences in the median values of IL-8 were observed between patients with and without SRILI. Patients who did not develop SRILI had approximately fourfold elevated levels of IL-8 as compared with patients who did subsequently develop SRILI. Significant correlations were not found for any other cytokine in this study, including transforming growth factor β1. Conclusions: Patients with lower levels of plasma IL-8 before radiation therapy might be at increased risk for developing SRILI. Further studies are necessary to determine whether IL-8 levels are predictive of SRILI in a prospective trial and whether this marker might be used to determine patient eligibility for dose escalation

  12. Cytokine medicines in clinical practice: current issues.

    Science.gov (United States)

    Barnes, Theresa; Moots, Robert J; Goodacre, John

    2005-10-21

    Cytokine medicines have been licensed for the treatment of rheumatoid arthritis since 2000. The rheumatology community has accrued a large amount of experience in the use of these medications. This experience has led to the development of guidelines for their use that include ongoing vigilance for long term adverse events and efficacy using the Biologics Register. Delivery of these expensive therapies has prompted extensive system developments within rheumatology. The cytokine medicines have provided important tools to probe the pathogenesis of rheumatoid and other inflammatory diseases. Further cytokine medicines, in various stages of development, are on the horizon and continue to stimulate excitement within this fast expanding field. PMID:16188452

  13. Selenium supplementation in patients undergoing hematopoietic stem cell transplantation: effects on pro-inflammatory cytokines levels

    OpenAIRE

    Daeian, Nesa; Radfar, Mania; Jahangard-Rafsanjani, Zahra; Hadjibabaie, Molouk; Ghavamzadeh, Ardeshir

    2014-01-01

    Background Pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) play an important role in the development of hematopoietic stem cell transplantation (HSCT) complications. We explored the effect of Selenium as an antioxidant and anti-inflammatory agent on pro-inflammatory cytokines levels in HSCT candidates. Findings Plasma concentrations of TNF-α, IL-1β and IL-6 were measured in 74 patients from a double-blind, randomized, p...

  14. Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza

    Directory of Open Access Journals (Sweden)

    Castro Carmen

    2011-08-01

    Full Text Available Abstract Background Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. Methods Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. Results Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p Conclusions Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.

  15. Rapid Detection of Neutrophil Oxidative Burst Capacity is Predictive of Whole Blood Cytokine Responses.

    Directory of Open Access Journals (Sweden)

    Philip J Vernon

    Full Text Available Maladaptive immune responses, particularly cytokine and chemokine-driven, are a significant contributor to the deleterious inflammation present in many types of injury and infection. Widely available applications to rapidly assess individual inflammatory capacity could permit identification of patients at risk for exacerbated immune responses and guide therapy. Here we evaluate neutrophil oxidative burst (NOX capacity measured by plate reader to immuno-type Rhesus Macaques as an acute strategy to rapidly detect inflammatory capacity and predict maladaptive immune responses as assayed by cytokine array.Whole blood was collected from anesthetized Rhesus Macaques (n = 25 and analyzed for plasma cytokine secretion (23-plex Luminex assay and NOX capacity. For cytokine secretion, paired samples were either unstimulated or ex-vivo lipopolysaccharide (LPS-stimulated (100μg/mL/24h. NOX capacity was measured in dihydrorhodamine-123 loaded samples following phorbol 12-myristate 13-acetate (PMA/ionomycin treatment. Pearson's test was utilized to correlate NOX capacity with cytokine secretion, p<0.05 considered significant.LPS stimulation induced secretion of the inflammatory molecules G-CSF, IL-1β, IL-1RA, IL-6, IL-10, IL-12/23(p40, IL-18, MIP-1α, MIP-1β, and TNFα. Although values were variable, several cytokines correlated with NOX capacity, p-values≤0.0001. Specifically, IL-1β (r = 0.66, IL-6 (r = 0.74, the Th1-polarizing cytokine IL-12/23(p40 (r = 0.78, and TNFα (r = 0.76 were strongly associated with NOX.NOX capacity correlated with Th1-polarizing cytokine secretion, indicating its ability to rapidly predict inflammatory responses. These data suggest that NOX capacity may quickly identify patients at risk for maladaptive immune responses and who may benefit from immuno-modulatory therapies. Future studies will assess the in-vivo predictive value of NOX in animal models of immune-mediated pathologies.

  16. Altered sodium intake affects plasma concentrations of BNP but not proBNP in healthy individuals and patients with compensated heart failure

    DEFF Research Database (Denmark)

    Damgaard, Morten; Goetze, Jens Peter; Norsk, Peter; Gadsbøll, Niels

    2007-01-01

    AIMS: Plasma B-type natriuretic peptide (BNP) and proBNP are promising markers for treatment of heart failure (HF), but the intra-individual biological variation is high. We investigated whether changes in sodium intake and posture contribute to this variation. METHODS AND RESULTS: A total of 12...... healthy individuals and 12 patients with medically treated compensated HF were examined after 1 week of low (70 mmol [1.61 g] per day) and 1 week of high (250 mmol [5.75 g] per day) sodium intake. Plasma volume and plasma concentrations of BNP and proBNP were determined after 1 h in seated and 1 h in...... supine position. In healthy individuals, the plasma BNP concentration increased significantly on high sodium intake with a ratio (high sodium/low sodium) of 2.00 (1.32-3.03, P = 0.004). The corresponding values for HF patients were 1.69 (1.25-2.29, P = 0.003). The plasma BNP concentration changed...

  17. Possible Impact of Salivary Influence on Cytokine Analysis in Exhaled Breath Condensate

    Directory of Open Access Journals (Sweden)

    T. Ichikawa

    2007-01-01

    Full Text Available Background: Exhaled breath condensate (EBC is thought to contain substances of the lower airway epithelial lining fluid (ELF aerosolized by turbulent flow. However, contamination by saliva may affect the EBC when collected orally.Objective: The purpose of this study was to compare the cytokine expression levels in EBC with those in saliva, and to clarify the influence of saliva on cytokine measurements of EBC.Methods: EBC and saliva samples were obtained from 10 adult subjects with stable asthma. To estimate differences in the contents of substances between EBC and saliva, the total protein concentration of each sample was measured. Further, we also measured the total protein concentration of ELF obtained from another patient group with suspected lung cancer using a micro sampling probe during bronchoscopic examination and roughly estimated the dilution of EBC by comparing the total protein concentration of EBC and ELF from those two patient groups. The cytokine expression levels of EBC and saliva from asthmatic group were assessed by a cytokine protein array.Results: The mean total protein concentrations in EBC, saliva and ELF were 4.6 μg/ml, 2,398 μg/ml and 14,111 μg/ml, respectively. The dilution of EBC could be estimated as 1:3000. Forty cytokines were analyzed by a cytokine protein array and each cytokine expression level of EBC was found to be different from that of saliva. Corrected by the total protein concentration, all cytokine expression levels of EBC were significantly higher than those of saliva.Conclusion: These results suggest that the salivary influence on the cytokine assessment in EBC may be negligible.

  18. Novel Flow Cytometry Analyses of Boar Sperm Viability: Can the Addition of Whole Sperm-Rich Fraction Seminal Plasma to Frozen-Thawed Boar Sperm Affect It?

    Science.gov (United States)

    Torres, Mariana Andrade; Díaz, Rommy; Boguen, Rodrigo; Martins, Simone Maria Massami Kitamura; Ravagnani, Gisele Mouro; Leal, Diego Feitosa; Oliveira, Melissa de Lima; Muro, Bruno Bracco Donatelli; Parra, Beatriz Martins; Meirelles, Flávio Vieira; Papa, Frederico Ozanan; Dell'Aqua, José Antônio; Alvarenga, Marco Antônio; Moretti, Aníbal de Sant'Anna; Sepúlveda, Néstor; de Andrade, André Furugen Cesar

    2016-01-01

    Boar semen cryopreservation remains a challenge due to the extension of cold shock damage. Thus, many alternatives have emerged to improve the quality of frozen-thawed boar sperm. Although the use of seminal plasma arising from boar sperm-rich fraction (SP-SRF) has shown good efficacy; however, the majority of actual sperm evaluation techniques include a single or dual sperm parameter analysis, which overrates the real sperm viability. Within this context, this work was performed to introduce a sperm flow cytometry fourfold stain technique for simultaneous evaluation of plasma and acrosomal membrane integrity and mitochondrial membrane potential. We then used the sperm flow cytometry fourfold stain technique to study the effect of SP-SRF on frozen-thawed boar sperm and further evaluated the effect of this treatment on sperm movement, tyrosine phosphorylation and fertility rate (FR). The sperm fourfold stain technique is accurate (R2 = 0.9356, p > 0.01) for simultaneous evaluation of plasma and acrosomal membrane integrity and mitochondrial membrane potential (IPIAH cells). Centrifugation pre-cryopreservation was not deleterious (p > 0.05) for any analyzed variables. Addition of SP-SRF after cryopreservation was able to improve total and progressive motility (p boar semen was cryopreserved without SP-SRF; however, it was not able to decrease tyrosine phosphorylation (p > 0.05) or improve IPIAH cells (p > 0.05). FR was not (p > 0.05) statistically increased by the addition of seminal plasma, though females inseminated with frozen-thawed boar semen plus SP-SRF did perform better than those inseminated with sperm lacking seminal plasma. Thus, we conclude that sperm fourfold stain can be used to simultaneously evaluate plasma and acrosomal membrane integrity and mitochondrial membrane potential, and the addition of SP-SRF at thawed boar semen cryopreserved in absence of SP-SRF improve its total and progressive motility. PMID:27529819

  19. PPARα/γ激动剂对糖尿病伴冠心病患者血浆炎症因子的影响%Effects of PPAR α/γ dual agonists on plasma inflammatory cytokine in patients with diabetes complicated with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    韦金儒; 唐泉

    2012-01-01

    'y-agonist on plasma concentrations of inflammatory cytokine in patients with diabetes mellitus complicated with coronary artery disease (CAD). Methods Eighty CAD patients were divided into four groups- rosiglitazone group (n=20), bezafibrate group (n=20), combination of rosiglitazone and bezafibrate group(n=20) and control group(n= 20). After treatment, patients were followed-up for 12 weeks. Plasma sample was collected from each patient before and after the treatment, respectively. Then plasma concentrations of C-reactive protein(CRP) and monocyte chemoatactic protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay. At the same time, the changes of fasting plasma glucose (FPC), fasting insulin, insulin resistance index (IRI), hemoglobin Ale (HbAlc), lipid and body mass index were also investigated. Results At the end of 12 weeks, patients in rosiglitazone group,bezafibrate group and combined rosiglitazone and bezafibrate group showed significantly reduction in plasma concentrations of CRP, MCP-1, FPG, insulin, IRI, HbAlc, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and increasion in concentration of high-density lipoprotein cholesterol (P<0.05), especially in combined rosiglitazone and bezafibrate group. Concentrations of MCP-1 secreted by monocyte which was induced by lipopolysaccharide in rosiglitazone group,bezafibrate group and combined rosiglitazone and bezafibrate group were siginificantly higher after 12 weeks treatment than thoae before treatment (P<0.05), and the decrease was most obviously in combined rosiglitazone and bezafibrate group. Decline in plasma concentrations of CRP appear to be correlated with the decrease of insulin (r=0.048,P<0.01) and insulin resistance index (r =0.496, P<0.001), but there was no correlation with other factors. Conclusions Combination of rosiglilazone and bezafibrale can increase insulin sensitivity, improve glucose metabolism and reduce the concentrations of CRP, MCP-1 in patients with diabetes

  20. Cytokines in the perinatal period - Part I.

    Science.gov (United States)

    Chau, A; Markley, J C; Juang, J; Tsen, L C

    2016-05-01

    Successful pregnancy requires a state of immune homeostasis. Maternal tolerance of the genetically distinct fetoplacental unit is in part mediated by maternal and fetal pro- and anti-inflammatory cytokines; these cytokines have also been implicated in different pregnancy-related pathologic states. This two-part series seeks to provide anesthesiologists with an overview on selected perinatal cytokines in an effort to identify opportunities for research and improvements in clinical care. In part one, we review basic and pregnancy-related elements of the immune system, with an emphasis on the role of cytokines. From this foundation, we offer a perspective of a unique phenomenon witnessed within obstetric anesthesia - maternal temperature elevation associated with labor epidural analgesia. PMID:26970932

  1. Biophysical studies of cytokine receptor interactions

    OpenAIRE

    Li, Jiejin; Dr. David Staunton

    2000-01-01

    The IL-6 family of cytokines includes IL-6, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), cardiotrophin-1, and IL-11. Functioning in a pleiotropic and redundant manner, these cytokines play an important role in the regulation of complex cellular processes such as gene activation, proliferation and differentiation, by signalling through homo- or heterodimers of gp130. This thesis describes the characterization of the interactions b...

  2. Cytokine profiles in asthma families depend on age and phenotype.

    Directory of Open Access Journals (Sweden)

    Katrin Pukelsheim

    Full Text Available BACKGROUND: Circulating cytokine patterns may be relevant for the diagnosis of asthma, for the discrimination of certain phenotypes, and prognostic factors for exacerbation of disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated serum samples from 944 individuals of 218 asthma-affected families by a multiplex, microsphere based system detecting at high sensitivity eleven asthma associated mediators: eotaxin (CCL11, granulocyte macrophage stimulating factor (GM-CSF, interferon gamma (IFNγ, interleukin-4 (IL-4, IL-5, IL-8, IL-10, IL-12 (p40, IL-13, IL-17 and tumor necrosis factor alpha (TNFα. Single cytokine levels were largely similar between asthmatic and healthy individuals when analysing asthma as single disease entity. Regulatory differences between parental and pediatric asthma were reflected by six of the eleven mediators analyzed (eotaxin, IL-4, IL-5, IL-10, IL-12, TNFα. IL-12 (p40 and IL-5 were the best predictor for extrinsic asthma in children with an increased odds ratio of 2.85 and 1.96 per log pg/ml increase (IL-12 (p40: 1.2-6.8, p=0.019, and IL-5: 1.2-2.5, p=0.025. Frequent asthma attacks in children are associated with elevated IL-5 serum levels (p=0.013. Cytokine patterns seem to be individually balanced in both, healthy and diseased adults and children, with various cytokines correlating among each other (IL-17 and IFNγ (rs=0.67, IL-4 and IL-5 (rs=0.55, IFNγ and GM-CSF (rs=0.54. CONCLUSION/SIGNIFICANCE: Our data support mainly an age- but also an asthma phenotype-dependent systemic immune regulation.

  3. Influence of acute hyperglycemia in human sepsis on inflammatory cytokine and counterregulatory hormone concentrations

    Institute of Scientific and Technical Information of China (English)

    Wen-Kui Yu; Wei-Qin Li; Ning Li; Jie-Shou Li

    2003-01-01

    AIM: In human sepsis, a prominent component of the hypermetabolite is impaired glucose tolerance (IGT) and hyperglycemia. Elevations in plasma glucose concentration impair immune function by altering cytokine production from macrophages. We assessed the role of glucose in the regulation of circulating levels of insulin, glucagon, cortisol,IL-6 and TNF-α in human sepsis with normal or impaired glucose tolerance.METHODS: According to the results of intravenous glucose tolerance test, forty patients were classified into two groups: control group (n=20) and IGT group (n=20).Plasma glucose levels were acutely raised in two groups and maintained at 15 mmol/L for 3 hours. Plasma insulin,glucagon and cortisol levels were measured by radioimmunoassay, the levels of TNF-α and IL-6 were detected by ELISA.RESULTS: In IGT group, the fasting concentrations of plasma glucose, insulin, glucagon, cortisol, IL-6 and TNFα levels were significantly higher than those in control group (P<0.05). During clamp, the control group had a higher average amount of dextrose infusion than the IGT group (P<0.01). In control group, plasma insulin levels rose from a basal value to a peak at an hour (P<0.05) and maintained at high levels. Plasma glucagon levels descended from a basal value to the lowest level within an hour (P<0.01)and low levels were maintained throughout the clamp. In IGT group, plasma insulin was more significantly elevated (P<0.01), and plasma glucagon levels were not significantly declined. Plasma cortisol levels were not significantly changed in two groups. In control group, plasma IL-6 and TNF-α levels rose (P<0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In IGT group, increased levels of plasma cytokine lasted longer than in control group (3 hours vs. 2 hours, P<0.05), and the cytokine peaks of IGT group were higher (P<0.05) than those of control group.CONCLUSION: Acute hyperglycemia pricks up hyperinsulinemia and increases

  4. Side effects of cytokines approved for therapy.

    Science.gov (United States)

    Baldo, Brian A

    2014-11-01

    Cytokines, currently known to be more than 130 in number, are small MW (aldesleukin (rhIL-2), oprelvekin (rhIL-11), filgrastim and tbo-filgrastim (rhG-CSF), sargramostim (rhGM-CSF), metreleptin (rh-leptin) and the rh-erythropoietins, epoetin and darbepoietin alfa. Anakinra, a recombinant receptor antagonist for IL-1, is in the IL-1 family; recombinant interferons alfa-1, alfa-2, beta-1 and gamma-1 make up the interferon family; palifermin (rhKGF) and becaplermin (rhPDGF) are in the PDGF family; and rhBMP-2 and rhBMP-7 represent the TGFβ family. The main physicochemical features, FDA-approved indications, modes of action and side effects of these approved cytokines are presented. Underlying each adverse events profile is their pleiotropism, potency and capacity to release other cytokines producing cytokine 'cocktails'. Side effects, some serious, occur despite cytokines being endogenous proteins, and this therefore demands caution in attempts to introduce individual members into the clinic. This caution is reflected in the relatively small number of cytokines currently approved by regulatory agencies and by the fact that 14 of the FDA-approved preparations carry warnings, with 10 being black box warnings. PMID:25270293

  5. Different environmental temperatures affect amino acid metabolism in the eurytherm teleost Senegalese sole (Solea senegalensis Kaup, 1858) as indicated by changes in plasma metabolites.

    NARCIS (Netherlands)

    Costas, B.; Aragao, C.; Ruiz-Jarabo, I.; Vargas-Chacoff, L.; Arjona, F.J.; Mancera, J.M.; Dinis, M.T.; Conceicao, L.E.

    2012-01-01

    Senegalese sole (Solea senegalensis) is a eurytherm teleost that under natural conditions can be exposed to annual water temperature fluctuations between 12 and 26 degrees C. This study assessed the effects of temperature on sole metabolic status, in particular in what concerns plasma free amino aci

  6. Cytokine orchestration in post-operative peritoneal adhesion formation.

    LENUS (Irish Health Repository)

    Cahill, Ronan A

    2012-02-03

    Peritoneal adhesions are a near inevitable occurrence after laparotomy and a major cause of both patient and physician misery. To date, clinical attempts at their amelioration have concentrated on manipulating the physical factors that affect their development despite a wealth of experimental data elucidating the molecular mechanisms that underlie their initiation, development and maturation. However, the advent of targeted, specific anti-cytokine agents as directed therapy for inflammatory and neoplastic conditions raises the prospect of a new era for anti-adhesion strategies. To harness this potential will require considerable cross-disciplinary collaboration and that surgeon-scientists propel themselves to the forefront of this emerging field.

  7. Fetuin-A induces cytokine expression and suppresses adiponectin production.

    Directory of Open Access Journals (Sweden)

    Anita M Hennige

    Full Text Available BACKGROUND: The secreted liver protein fetuin-A (AHSG is up-regulated in hepatic steatosis and the metabolic syndrome. These states are strongly associated with low-grade inflammation and hypoadiponectinemia. We, therefore, hypothesized that fetuin-A may play a role in the regulation of cytokine expression, the modulation of adipose tissue expression and plasma concentration of the insulin-sensitizing and atheroprotective adipokine adiponectin. METHODOLOGY AND PRINCIPAL FINDINGS: Human monocytic THP1 cells and human in vitro differenttiated adipocytes as well as C57BL/6 mice were treated with fetuin-A. mRNA expression of the genes encoding inflammatory cytokines and the adipokine adiponectin (ADIPOQ was assessed by real-time RT-PCR. In 122 subjects, plasma levels of fetuin-A, adiponectin and, in a subgroup, the multimeric forms of adiponectin were determined. Fetuin-A treatment induced TNF and IL1B mRNA expression in THP1 cells (p<0.05. Treatment of mice with fetuin-A, analogously, resulted in a marked increase in adipose tissue Tnf mRNA as well as Il6 expression (27- and 174-fold, respectively. These effects were accompanied by a decrease in adipose tissue Adipoq mRNA expression and lower circulating adiponectin levels (p<0.05, both. Furthermore, fetuin-A repressed ADIPOQ mRNA expression of human in vitro differentiated adipocytes (p<0.02 and induced inflammatory cytokine expression. In humans in plasma, fetuin-A correlated positively with high-sensitivity C-reactive protein, a marker of subclinical inflammation (r = 0.26, p = 0.01, and negatively with total- (r = -0.28, p = 0.02 and, particularly, high molecular weight adiponectin (r = -0.36, p = 0.01. CONCLUSIONS AND SIGNIFICANCE: We provide novel evidence that the secreted liver protein fetuin-A induces low-grade inflammation and represses adiponectin production in animals and in humans. These data suggest an important role of fatty liver in the pathophysiology of insulin resistance and

  8. Insulin Resistance and Increased Muscle Cytokine Levels in Patients With Mitochondrial Myopathy

    DEFF Research Database (Denmark)

    Rue, Nana; Vissing, John; Galbo, Henrik

    2014-01-01

    CONTEXT: Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production. OBJECTIVE: The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle. DESIGN AND......), identically in P and C. No differences existed in plasma cytokine concentrations. CONCLUSIONS: In patients with a variety of mitochondrial myopathies, insulin sensitivity of muscle, adipose tissue, and pancreatic A cells is reduced, supporting that mitochondrial function influences insulin action. Furthermore...... intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed. MAIN OUTCOME MEASURES: Glucose infusion rate during 90-120 minutes of insulin infusion...

  9. A low-saturated-fat, low-cholesterol diet decreases plasma CETP activity and pre beta-HDL formation but does not affect cellular cholesterol efflux to plasma from type 1 diabetic patients

    NARCIS (Netherlands)

    De Vries, R; Beusekamp, BJ; Kerstens, MN; Groen, AK; Van Tol, A; Dullaart, RPF

    2005-01-01

    The aim of this study was to evaluate the effect of a low-saturated-fat, low-cholesterol diet on plasma lipopoproteins, pre beta-high density lipoprotein (HDL) formation, lecithin: cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP)

  10. Plasmas for space propulsion

    Science.gov (United States)

    Ahedo, Eduardo

    2011-12-01

    Plasma thrusters are challenging the monopoly of chemical thrusters in space propulsion. The specific energy that can be deposited into a plasma beam is orders of magnitude larger than the specific chemical energy of known fuels. Plasma thrusters constitute a vast family of devices ranging from already commercial thrusters to incipient laboratory prototypes. Figures of merit in plasma propulsion are discussed. Plasma processes and conditions differ widely from one thruster to another, with the pre-eminence of magnetized, weakly collisional plasmas. Energy is imparted to the plasma via either energetic electron injection, biased electrodes or electromagnetic irradiation. Plasma acceleration can be electrothermal, electrostatic or electromagnetic. Plasma-wall interaction affects energy deposition and erosion of thruster elements, and thus is central for thruster efficiency and lifetime. Magnetic confinement and magnetic nozzles are present in several devices. Oscillations and turbulent transport are intrinsic to the performances of some thrusters. Several thrusters are selected in order to discuss these relevant plasma phenomena.

  11. Respiratory Mechanics and Plasma Levels of Tumor Necrosis Factor Alpha and Interleukin 6 Are Affected by Gas Humidification during Mechanical Ventilation in Dogs

    OpenAIRE

    HERNÁNDEZ-JIMÉNEZ, CLAUDIA; García-Torrentera, Rogelio; Olmos-Zúñiga, J. Raúl; Jasso-Victoria, Rogelio; Miguel O Gaxiola-Gaxiola; Baltazares-Lipp, Matilde; Gutiérrez-González, Luis H.

    2014-01-01

    The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group ...

  12. Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

    Directory of Open Access Journals (Sweden)

    Claudia Hernández-Jiménez

    Full Text Available The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5, mechanical ventilation with dry oxygen dispensation, and Group II (n = 5, mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77. This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05. Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02. Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

  13. Pseudomonas aeruginosa and Its Bacterial Components Influence the Cytokine Response in Thymocytes and Splenocytes.

    Science.gov (United States)

    Weber, Andreas; Zimmermann, Corinna; Mausberg, Anne K; Dehmel, Thomas; Kieseier, Bernd C; Hartung, Hans-Peter; Hofstetter, Harald H

    2016-05-01

    Infections with Pseudomonas aeruginosa may cause many different diseases. The spectrum of such infections in general includes inflammation and bacterial sepsis. Hospital-acquired pneumonia, naturally resistant to a wide range of antibiotics, is associated with a particularly high mortality rate in mechanically ventilated patients. The pathogenesis of P. aeruginosa is complex and mediated by several virulence factors, as well as cell-associated factors. We have previously demonstrated that stimulation with different bacteria triggers the cytokine response of thymocytes. In this study, we investigated the effect of P. aeruginosa and its different components on the cytokine production of immature and mature immune cells. We found that the induced cytokine pattern in the thymus and the spleen after infections with P. aeruginosa is primarily mediated by lipopolysaccharide (LPS) of the outer cell membrane, but other components of the bacterium can influence the cytokine secretion as well. Stimulation with heat-killed P. aeruginosa and LPS does not influence the amount of cytokine-producing CD4(+) T cells but instead suppresses the emergence of Th17 cells. However, stimulation with P. aeruginosa or its components triggers the interleukin-17 (IL-17) response both in thymocytes and in splenocytes. We conclude that infections with P. aeruginosa affect the cytokine secretion of immature and mature cells and that IL-17 and Th17 cells play only a minor role in the development of pathological systemic inflammatory disease conditions during P. aeruginosa infections. Therefore, other inflammatory immune responses must be responsible for septic reactions of the host. PMID:26902726

  14. Cytokine Gene Polymorphisms in Egyptian Cases with Brain Tumors

    International Nuclear Information System (INIS)

    Background: Cytokines are proposed to play important roles in brain tumor biology as well as neuro degeneration or impaired neuronal function. Objectives: This work aimed to check the association of polymorphisms of cytokine genes in Egyptian cases with brain tumors. Methods: This work included 45 cases affected by brain tumors diagnosed as 24 benign and 21 malignant. Their median age was 45 years, and they were 20 males and 25 females. These cases were taken randomly from the Neurosurgery Department of Mansoura University Hospital, Egypt. Case genotypes were compared to 98 healthy unrelated controls from the same locality. DNA was amplified using PCR utilizing sequence specific primers (SSP) for detection of polymorphisms related to TNF-a-308 (G/A), IL-10-1082 (G/A), IL-6-174 (G/C) and IL-1Ra (VNTR) genes. Results: Cases affected with benign brain tumors showed a significant higher frequency of IL-10-1082 A/A [odds ratio (OR=8.0), p<0.001] and IL-6-174 C/C (OR=6.3, p=0.002) homozygous genotypes as compared to controls. Malignant cases, on the other hand, showed significantly higher frequency of IL-6-174 C/C (OR =4.8, p=0.002) homozygous genotype and TNF-a-308 A/A (OR=4.9, p<0.001) homozygous genotype when compared to controls. In the meantime, all cases showed no significant difference regarding the distribution of IL-1Ra VNTR genotype polymorphism compared to controls. Conclusions: Cytokine gene polymorphisms showed a pattern of association with brain tumors which may have potential impact on family counseling and disease management.

  15. Cytokine expression profile of dengue patients at different phases of illness.

    Directory of Open Access Journals (Sweden)

    Anusyah Rathakrishnan

    Full Text Available BACKGROUND: Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease. METHODS AND FINDINGS: Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1β was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1β and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study. CONCLUSIONS: The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.

  16. Regulation of human cytokines by Cordyceps militaris

    Directory of Open Access Journals (Sweden)

    Yong Sun

    2014-12-01

    Full Text Available Cordyceps (Cordyceps militaris exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits. In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70, interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines.

  17. Interleukin-1 Family Cytokines in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Hiroko Tsutsui

    2015-01-01

    Full Text Available The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra, and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation. Some require inflammasome-mediated processing for activation and release, whereas others serve as alarmins and are released following cell membrane rupture, for example, by pyroptosis or necroptosis. Thus, each ligand has the proper molecular process to exert its own biological functions. In this review, we will give a brief introduction to the IL-1 family cytokines and discuss their pivotal roles in the development of various liver diseases in association with immune responses. For example, an excess of IL-33 causes liver fibrosis in mice via activation and expansion of group 2 innate lymphoid cells to produce type 2 cytokines, resulting in cell conversion into pro-fibrotic M2 macrophages. Finally, we will discuss the importance of IL-1 family cytokine-mediated molecular and cellular networks in the development of acute and chronic liver diseases.

  18. Role of cytokines in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Fausto Sanchez-Muñoz, Aaron Dominguez-Lopez, Jesus K Yamamoto-Furusho

    2008-07-01

    Full Text Available Inflammatory bowel disease (IBD, which includes Crohn’s disease (CD and ulcerative colitis (UC, represents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. Mucosal macrophages play an important role in the mucosal immune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major contributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of the inflammatory process in IBD. Therefore, several cytokine therapies have been developed and tested for the treatment of IBD patients.

  19. Study on the inter-relationship between serum cytokines levels and severity of type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Objective: To investigate the role played by serum cytokines (IL-6, IL-8, TNF-α) in the pathogenesis of diabetes mellitus. Methods: Serum IL-6, IL-8 and TNF-α levels were measured with RIA in 27 diabetic patients without complications, 18 patients with early nephro or retinopathy and 33 controls. Results: (1) Serum levels of IL-6, IL-8 and TNF-α were significantly higher in the diabetic patients than those in controls (P<0.01). (2) Levels of the cytokines in diabetic patients with early complications were significantly higher than those in patients without complications (P<0.02). (3) The serum levels of these cytokines were mutually positively correlated. Conclusion: The cytokines IL-6, IL-8 and TNF-α participated in the development and pathophysiology of diabetes mellitus and monitoring their plasma level changes would be clinically useful. (authors)

  20. The peri-operative cytokine response in infants and young children following major surgery

    DEFF Research Database (Denmark)

    Hansen, Tom Giedsing; Tønnesen, Else Kirstine; Andersen, J B; Toft, P; Bendtzen, Klaus

    1998-01-01

    The peri-operative cytokine response was studied in 13 infants and young children undergoing major surgery. All children were anaesthetized with a combined general and epidural anaesthetic technique, followed by post-operative epidural analgesia with bupivacaine and fentanyl. Blood samples were...... taken before and after surgery, 24 h post-operatively, and finally, when the children were mobilized and had regained gastrointestinal function. Plasma samples were analysed for tumour necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interferon-gamma, interleukin-10 and the...... interleukin-1 receptor antagonist. The cytokine responses were highly variable. Overall, no significant changes between pre- and post-operative plasma concentrations were found. Tumour necrosis factor-alpha and the interleukin-1 receptor antagonist were detectable in all children, and a trend towards an early...

  1. Determination of blood ET-1 and related cytokines in pediatric patients with bronchial asthma

    International Nuclear Information System (INIS)

    Objective: To explore the role of endothelin and related cytokines (IL-5, IL-6, IL-8) in the development of bronchial asthma in pediatric patients. Methods: Plasma ET-1 (with RIA) and serum IL-5 (with ELISA), IL-6, IL-8 (with RIA) levels were measured in 42 pediatric patients with bronchial asthma and 30 controls. Results: The plasma ET-1 levels in the patients during acute attack (n=22) were significantly higher than those in patients during remission (n=20) as well as in controls (P0.05). Levels of ET-1 were positively correlated with those of IL-5 (during attack, r=0.560, P<0.01; during remission, r=0.435, P<0.01). Conclusion: ET and the cytokines IL-5, IL-6, IL-8 participated in the pathogenesis of bronchial asthma through different mechanisms and dynamic determination of which could reflect the progression of the disease. (authors)

  2. Th1/Th2 Cytokines in Psoriasis

    Directory of Open Access Journals (Sweden)

    Z Jadali

    2007-08-01

    Full Text Available Background: The aim of this study was to determine the Th1 and Th2 serum cytokines, in patients with psoriasis and to com¬pare their cytokine levels with those of normal control subjects. Methods: Serum levels of Interferon-gamma (IFN-γ, Interleukin-2 (IL-2, Interleukin-4 (IL-4, and Interleukin-10 (IL-10 were measured by enzyme linked immunosorbent assay in 40 patients with psoriasis and in 40 normal controls. Results: Compared with control subjects, patients with psoriasis had elevated levels of IFN-γ and IL-2 (P<0.001. In addi¬tion a positive correlation was found between the levels of IFN-γ, IL-2 and disease severity. Conclusion: Th1 secreting inflammatory cytokines may contribute to the pathogenesis of psoriasis.

  3. [Plant-Producers Of Recombinant Cytokines (Review)].

    Science.gov (United States)

    Burlakovskii, M S; Yemel'yanov, V V; Lutova, L A

    2016-01-01

    Cytokines are a family of signaling polypeptides involved in cell-cell interactions in the process of the immune response, as well as in the regulation of a number of normal physiological functions. Cytokines are used in medicine for the treatment of cancer, immune disorders, viral infections, and other socially significant diseases, but the extent of their use is limited by the high production cost of the active agent. The development of this area of pharmacology is associated with the success of genetic engineering, which allows the production of significant amounts of protein by transgenic organisms. The review discusses the latest advances in the production of various cytokines with the use of genetically modified plants. PMID:27266244

  4. Changes in the electro-physical properties of MCT epitaxial films affected by a plasma volume discharge induced by an avalanche beam in atmospheric-pressure air

    Science.gov (United States)

    Grigoryev, D. V.; Voitsekhovskii, A. V.; Lozovoy, K. A.; Tarasenko, V. F.; Shulepov, M. A.

    2015-11-01

    In this paper the influence of the plasma volume discharge of nanosecond duration formed in a non-uniform electric field at atmospheric pressure on samples of epitaxial films HgCdTe (MCT) films are discussed. The experimental data show that the action of pulses of nanosecond volume discharge in air at atmospheric pressure leads to changes in the electrophysical properties of MCT epitaxial films due to formation of a near-surface high- conductivity layer of the n-type conduction. The preliminary results show that it is possible to use such actions in the development of technologies for the controlled change of the properties of MCT.

  5. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However, these...

  6. Cytokine inhibition in the treatment of COPD

    Directory of Open Access Journals (Sweden)

    Caramori G

    2014-04-01

    Full Text Available Gaetano Caramori,1 Ian M Adcock,2,3 Antonino Di Stefano,4 Kian Fan Chung2,3 1Dipartimento di Scienze Mediche, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO, Sezione di Medicina Interna e Cardiorespiratoria, Università di Ferrara, Ferrara, Italy; 2Airway Diseases Section, National Heart and Lung Institute, Imperial College London, UK; 3Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK; 4Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio-Respiratorio, Fondazione Salvatore Maugeri, IRCCS, Veruno, Italy Abstract: Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD, including the chronic inflammatory process, emphysema, and altered innate immune response. Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF-α, interferon-γ, interleukin (IL-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP, and growth factors such as transforming growth factor-β. The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations. While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable. In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines. The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor. Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in

  7. Changes of inflammation-associated cytokine expressions during early phase of experimental endotoxic shock in macaques

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Ji; Ke-Yi Sun; Yan-Hong Feng; Guo-Qing Yin

    2004-01-01

    AIM: To study changes of inflammation-associated cytokine expressions during early phase of endotoxic shock in macague.METHODS: Experiments were performed in Macaque mulatta treated with LPS 2.8 mg/kg in shock model group or with normal saline in control group. Blood samples were collected before, or 60 min, or 120 min after LPS injection,respectively. Liver and spleen tissues were obtained at 120 min after LPS injection. The plasma levels of TNF-α,IL-1 β, IL-10 and IL-12P40 were determined by doubleantibody sandwich ELISA with antibodies against human cytokines. The mRNA levels of TNF-α, IL-1 β, and IL-18 in peripheral blood mononuclear cells (PBMCs), liver and spleen were examined by real-time fluorescence semi-quantitative RT-PCR with the primers based on human genes.RESULTS: Mean systemic arterial pressure (MAP), systemic vascular resistance index (SVRI) and left ventricular work index (LVWI) of macaques were significant declined in shock model group on average 60 min after LPS injection. The plasma levels of TNF-α and IL-10 were significantly increased 60 min after LPS injection and then decreased.The plasma levels of IL-1 β and IL-12P40 were significantly increased at 120 min after LPS injection. The mRNA levels of TNF-α and IL-1 β were significantly increased 60 min after LPS stimulation in PBMCs and 120 min after LPS stimulation in livers. The mRNA level of IL-18 was significantly increased 120 min after LPS stimulation in PBMCs and livers. But in spleen, only TNF-α mRNA level in LPS group was significantly higher 120 min after LPS stimulation, compared with that in control group.CONCLUSION: An endotoxic shock model of Macaque mulatta was successfully established. Both antibodies for ELISA and PCR primers based on human cytokine assays were successfully applied to detect macaque cytokines. In the model, inflammatory cytokines, such as TNF-α, IL-1 β,IL-12 and IL-18 as well as anti-inflammation cytokine IL-10,were released at very early phase of

  8. Plasmas for space propulsion

    International Nuclear Information System (INIS)

    Plasma thrusters are challenging the monopoly of chemical thrusters in space propulsion. The specific energy that can be deposited into a plasma beam is orders of magnitude larger than the specific chemical energy of known fuels. Plasma thrusters constitute a vast family of devices ranging from already commercial thrusters to incipient laboratory prototypes. Figures of merit in plasma propulsion are discussed. Plasma processes and conditions differ widely from one thruster to another, with the pre-eminence of magnetized, weakly collisional plasmas. Energy is imparted to the plasma via either energetic electron injection, biased electrodes or electromagnetic irradiation. Plasma acceleration can be electrothermal, electrostatic or electromagnetic. Plasma–wall interaction affects energy deposition and erosion of thruster elements, and thus is central for thruster efficiency and lifetime. Magnetic confinement and magnetic nozzles are present in several devices. Oscillations and turbulent transport are intrinsic to the performances of some thrusters. Several thrusters are selected in order to discuss these relevant plasma phenomena.

  9. Intensive Cytokine induction in Pandemic H1N1 Influenza Virus Infection Accompanied by Robust Production of IL-10 and IL-6

    OpenAIRE

    Yu, Xuelian; Zhang, Xi; Zhao, Baihui; Wang, Jiayu; Zhu, Zhaokui; Teng, Zheng; Shao, Junjie; Shen, Jiaren; Gao, Ye; Yuan, Zhengan; Wu, Fan

    2011-01-01

    Background The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severi...

  10. Plasma dynamo

    CERN Document Server

    Rincon, F; Schekochihin, A A; Valentini, F

    2015-01-01

    Magnetic fields pervade the entire Universe and, through their dynamical interactions with matter, affect the formation and evolution of astrophysical systems from cosmological to planetary scales. How primordial cosmological seed fields arose and were further amplified to $\\mu$Gauss levels reported in nearby galaxy clusters, near equipartition with kinetic energy of plasma motions and on scales of at least tens of kiloparsecs, is a major theoretical puzzle still largely unconstrained by observations. Extragalactic plasmas are weakly collisional (as opposed to collisional magnetohydrodynamic fluids), and whether magnetic-field growth and its sustainment through an efficient dynamo instability driven by chaotic motions is possible in such plasmas is not known. Fully kinetic numerical simulations of the Vlasov equation in a six-dimensional phase space necessary to answer this question have until recently remained beyond computational capabilities. Here, we show by means of such simulations that magnetic-field a...

  11. Cytokines and Metabolic Patterns in Pediatric Patients with Critical Illness

    Directory of Open Access Journals (Sweden)

    George Briassoulis

    2010-01-01

    Full Text Available It is not known if cytokines, which are cell-derived mediators released during the host immune response to stress, affect metabolic response to stress during critical illness. The aim of this prospective study was to determine whether the metabolic response to stress is related to the inflammatory interleukin-6 (IL-6, 10 (IL-10, and other stress mediators' responses and to assess their relationships with different feeding patterns, nutritional markers, the severity of illness as assessed by the Multiple Organ System Failure (MOSF, the Pediatric Risk of Mortality Score (PRISM, systemic inflammatory response syndrome (SIRS, and mortality in critically ill children. Patients were classified as hypermetabolic, normometabolic, and hypometabolic when the measured resting energy expenditures (REE were >110%, 90–110% and, <90% of the predicted basal metabolic rate, respectively. The initial predominance of the hypometabolic pattern (48.6% declined within 1 week of acute stress (20%, and the hypermetabolic patterns dominated only after 2 weeks (60%. Only oxygen consumption (VO2 and carbon dioxide production (VCO2 (<.0001 but none of the cytokines and nutritional markers, were independently associated with a hypometabolic pattern. REE correlated with the IL-10 but not PRISM. In the presence of SIRS or sepsis, CRP, IL-6, IL-10, Prognostic Inflammatory and Nutritional Index (NI, and triglycerides—but not glucose, VO2, or VCO2 increased significantly. High IL-10 levels (=.0000 and low measured REE (=.0000 were independently associated with mortality (11.7%, which was higher in the hypometabolic compared to other metabolic patterns (<.005. Our results showed that only VO2 and VCO2, but not IL-6 or IL-10, were associated with a hypometabolic pattern which predominated the acute phase of stress, and was associated with increased mortality. Although in SIRS or sepsis, the cytokine response was reliably reflected by increases in NI and triglycerides, it was

  12. T-lymphocyte cytokine profiles in compositae airborne dermatitis.

    Science.gov (United States)

    Stingeni, L; Agea, E; Lisi, P; Spinozzi, F

    1999-10-01

    Compositae airborne dermatitis is a well-recognized disorder characterized by erythematosquamous lesions and papules on light-exposed areas. The presence of positive patch test reactions and the absence of specific serum IgE suggest delayed-type hypersensitivity, the murine model of which is characterized by a Th1 cytokine production profile [high amounts of interferon (IFN)-gamma and interleukin (IL)-2; little or no IL-4 and IL-5]. The aim of this study was to evaluate the cytokine profile of T-cell lines and T-cell clones from peripheral blood in a 38-year-old non-atopic male woodcutter affected by seasonal airborne contact dermatitis. The patient showed positive patch test reactions to several Compositae extracts (Achillea millefolium, Chamomilla recutita, Tanacetum parthenium, T. vulgare) and sesquiterpene lactone mix. On prick testing with Compositae and other plants, serum-specific IgE levels and phototesting were negative or normal. Allergen-specific T-cell lines produced with Compositae extracts showed a good in vitro cell proliferation only to C. recutita extract. Serial cloning performed using the C. recutita-specific T-cell lines revealed an alphabeta+CD4+ phenotype with high amounts of IFN-gamma and IL-4 in T-cell clones. Thus, these cells expressed a preferential Th0 phenotype. These data suggest that in addition to IFN-gamma, other T-cell derived cytokines, such as IL-4, may play a part in the immunopathogenesis of contact dermatitis. PMID:10583117

  13. [Cytokines in the treatment of blood diseases].

    Science.gov (United States)

    Robak, T

    1995-01-01

    Cytokines are a class of signal peptides which represent a major communication network in living organism. Over the last decade, the discovery, cloning and purification of hematopoietic cytokines (interleukins, hematopoietic growth factors) has increased our understanding of the regulation, proliferation, differentiation and function of hematopoietic cells. More recently, the large scale production of the recombinant forms of these molecules has enabled to treat the patients with pharmacologic doses of cytokines. The therapeutic activity of interferon-alpha (IFN-alpha) has been demonstrated in patients with chronic myeloid leukaemia and other chronic myeloproliferative syndromes. IFN-gamma is useful in the prevention of infections in patients with chronic granulomatous disease. Erythropoietin (EPO) was the first hematopoietic growth factor available for clinical use, initially to treat anaemia in renal failure patients. The next cytokines introduced into the clinic were granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF). They are used successfully in haematological malignant disorders to stimulate granulopoiesis after chemotherapy or bone marrow transplantation and to help mobilise marrow stem cells for peripheral blood stem cell transplantation. Interleukin (IL)-1, -2, -3, -4, -6 and -11 have been tested in clinical trials. However, the value of these agents remains to be established. PMID:7544526

  14. Cytokines and Chemokines in Irritant Contact Dermatitis

    OpenAIRE

    Haur Yueh Lee; Marco Stieger; Nikhil Yawalkar; Masato Kakeda

    2013-01-01

    Irritant contact dermatitis is a result of activated innate immune response to various external stimuli and consists of complex interplay which involves skin barrier disruption, cellular changes, and release of proinflammatory mediators. In this review, we will focus on key cytokines and chemokines involved in the pathogenesis of irritant contact dermatitis and also contrast the differences between allergic contact dermatitis and irritant contact dermatitis.

  15. IFN-gamma: Novel antiviral cytokines

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Paludan, Søren Riis

    2006-01-01

    adaptive immune responses. Recently, a novel class of cytokines was discovered and named IFN-lambda (alternatively type III IFN or interleukin-28/29 [IL- 28/29]), based on IFN-like antiviral activity and induction of typical IFN-inducible genes. Here, we review the literature on IFN-lambda and discuss the...

  16. CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS

    Science.gov (United States)

    CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS. LM Plitnick1, SE Loveless2, GS Ladics2, MP Holsapple3, MJ Selgrade4, DM Sailstad4 & RJ Smialowicz4. 1UNC, Chapel Hill, NC; 2DuPont Co., Haskell Laboratory, Newark, DE; 3Dow Chemical, Midland, MI & 4USEPA, NHEERL, RTP, NC.

  17. Circulating cytokines in patients undergoing organ transplantation

    Czech Academy of Sciences Publication Activity Database

    Vondráček, Jan; Lojek, Antonín; Černý, J.; Číž, Milan; Němec, P.; Čížová, Hana; Dušková, Monika; Wagner, R.; Níčovský, J.

    Hradec Králové : Purkyně Military Medical Academy, 1995. s. 27-32. [Experimental, Therapeutic and Toxic Manipulations of Host Defence System. 12.06.1995-15.06.1995, Hradec Králové] Keywords : cytokines * transplantation * ischemia/reperfusion * kidney * liver * heart

  18. Cytokines and the hepatic acute phase response

    NARCIS (Netherlands)

    Moshage, H

    1997-01-01

    The acute phase response is an orchestrated response to tissue injury, infection or inflammation. A prominent feature of this response is the induction of acute phase proteins, which are involved in the restoration of homeostasis. Cytokines are important mediators of the acute phase response. Uncont

  19. Divergent effects of Tenofovir and Retrovir (AZT) on TLR-mediated cytokine production

    DEFF Research Database (Denmark)

    Melchjorsen, Jesper; Tolstrup, Martin; Paludan, Søren Riis; Østergaard, Lars Jørgen

      Pathogen-recognizing Toll-like receptors 2 (TLR2) and TLR4 are known to recognize a number of pathogens, including E.Coli, S. Pneumoniae and N. Meningitidis. We have studied whether a number of HIV therapeutics affect immediate proinflammatory cytokine responses in cell cultures. Preliminary re...... results suggest an opposing effect of the drugs Tenofovir and Retrovir (AZT) on TLR-mediated proinflammatory cytokine production. We present data on the mechanisms behind the drug-mediated remodeling of innate immune activation and how the drugs effect early host-pathogen interactions....

  20. Exposure of human islets to cytokines can result in disproportionately elevated proinsulin release

    OpenAIRE

    Hostens, Katleen; Pavlovic, Dejan; Zambre, Yasmeeni; Ling, Zhidong; Van Schravendijk, Christiaan; Eizirik, Décio L.; Pipeleers, Daniel G.

    1999-01-01

    Infiltration of immunocytes into pancreatic islets precedes loss of β cells in type 1 diabetes. It is conceivable that local release of cytokines affects the function of β cells before their apoptosis. This study examines whether the elevated proinsulin levels that have been described in prediabetes can result from exposure of β cells to cytokines. Human β-cell preparations were cultured for 48 or 72 hours with or without IL-1β, TNF-α, or IFN-γ, alone or in combination. None of these conditio...

  1. INTERACTION OF CYTOKINE CASCADE WITH PSYCHOLOGICAL PROFILE IN PATIENTS WITH ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    M. A. Shalenkova

    2013-01-01

    Full Text Available Abstract. The role of immune factors in development of atherosclerotic process and anxiety-depressive disorders is of utmost importance. Serum levels of IL-6 and -10 were studied in forty-nine patients with acute coronary syndrome, as well as their interactions with psychological state of the patients. Serum concentrations of the cytokines proved to be higher in unstable angina. A correlation was confirmed between the cytokine levels and co-morbidity with affective disorders in acute ischaemic heart disease.

  2. 精子脂质过氧化反应与致炎细胞因子%Sperm lipid peroxidation and pro-inflammatory cytokines

    Institute of Scientific and Technical Information of China (English)

    P.Martinez; F.Proverbio; M.I.Camejo

    2007-01-01

    Aim:To investigate if interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-gamma (IFN-γ) or tumor necrosis factor-alpha (TNF-α) are able to stimulate the level of lipid peroxidation of sperm membranes, either alone or in the presence of leukocytes. Methods: Semen samples from normozoospermic donors were prepared by density gradient. The sperms were exposed to the indicated cytokines, at physiological and infection-inflammation concentrations, in the absence or presence of leukocytes. Lipid peroxidation of the sperm membranes was determined by measuring malondialdehyde (MDA) and 4-hydroxialkenals (HAE) formation. Results: TNF-α, IL-8 and IFN-γ increased the level of sperm membrane lipid peroxidation when tested at physiological concentrations. At infectioninflammation concentrations, only IL-8 was able to produce a higher effect. When assayed in the presence of leucocytes,IL-8 and TNF-α showed a higher effect at infection-inflammation concentrations than at physiological concentrations.Finally, IL-8 showed a higher effect in the presence of leukocytes than in their absence at both physiological and infection-inflammation concentrations. TNF-α also showed a higher effect when assayed in the presence of leukocytes than in their absence, but only at infection-inflammation concentrations. There was no effect of IL-6 or IL- 10 in any of the tested conditions. Conclusion: Several pro-inflammatory cytokines at physiological concentrations increase the level of lipid peroxidation of sperm membranes, which could be important for the sperm fecundation process. However, infection-inflammation concentrations of some cytokines, such as IL-8 and TNF-α, either alone or in the presence of leukocytes, could drive the lipid peroxidation of the spermatozoa plasma membrane to levels that can affect the sperm fertility capacity.

  3. Surface plasma functionalization influences macrophage behavior on carbon nanowalls

    Energy Technology Data Exchange (ETDEWEB)

    Ion, Raluca [University of Bucharest, Department of Biochemistry and Molecular Biology, 91-95 Spl. Independentei, 050095 Bucharest (Romania); Vizireanu, Sorin [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania); Stancu, Claudia Elena [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania); Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany); Luculescu, Catalin [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania); Cimpean, Anisoara, E-mail: anisoara.cimpean@bio.unibuc.ro [University of Bucharest, Department of Biochemistry and Molecular Biology, 91-95 Spl. Independentei, 050095 Bucharest (Romania); Dinescu, Gheorghe [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania)

    2015-03-01

    The surfaces of carbon nanowall samples as scaffolds for tissue engineering applications were treated with oxygen or nitrogen plasma to improve their wettability and to functionalize their surfaces with different functional groups. X-ray photoelectron spectroscopy and water contact angle results illustrated the effective conversion of the carbon nanowall surfaces from hydrophobic to hydrophilic and the incorporation of various amounts of carbon, oxygen and nitrogen functional groups during the treatments. The early inflammatory responses elicited by un-treated and modified carbon nanowall surfaces were investigated by quantifying tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha released by attached RAW 264.7 macrophage cells. Scanning electron microscopy and fluorescence studies were employed to investigate the changes in macrophage morphology and adhesive properties, while MTT assay was used to quantify cell proliferation. All samples sustained macrophage adhesion and growth. In addition, nitrogen plasma treatment was more beneficial for cell adhesion in comparison with un-modified carbon nanowall surfaces. Instead, oxygen plasma functionalization led to increased macrophage adhesion and spreading suggesting a more activated phenotype, confirmed by elevated cytokine release. Thus, our findings showed that the chemical surface alterations which occur as a result of plasma treatment, independent of surface wettability, affect macrophage response in vitro. - Highlights: • N{sub 2} and O{sub 2} plasma treatments alter the CNW surface chemistry and wettability. • Cells seeded on CNW scaffolds are viable and metabolically active. • Surface functional groups, independent of surface wettability, affect cell response. • O{sub 2} plasma treatment of CNW leads to a more activated macrophage phenotype.

  4. Surface plasma functionalization influences macrophage behavior on carbon nanowalls

    International Nuclear Information System (INIS)

    The surfaces of carbon nanowall samples as scaffolds for tissue engineering applications were treated with oxygen or nitrogen plasma to improve their wettability and to functionalize their surfaces with different functional groups. X-ray photoelectron spectroscopy and water contact angle results illustrated the effective conversion of the carbon nanowall surfaces from hydrophobic to hydrophilic and the incorporation of various amounts of carbon, oxygen and nitrogen functional groups during the treatments. The early inflammatory responses elicited by un-treated and modified carbon nanowall surfaces were investigated by quantifying tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha released by attached RAW 264.7 macrophage cells. Scanning electron microscopy and fluorescence studies were employed to investigate the changes in macrophage morphology and adhesive properties, while MTT assay was used to quantify cell proliferation. All samples sustained macrophage adhesion and growth. In addition, nitrogen plasma treatment was more beneficial for cell adhesion in comparison with un-modified carbon nanowall surfaces. Instead, oxygen plasma functionalization led to increased macrophage adhesion and spreading suggesting a more activated phenotype, confirmed by elevated cytokine release. Thus, our findings showed that the chemical surface alterations which occur as a result of plasma treatment, independent of surface wettability, affect macrophage response in vitro. - Highlights: • N2 and O2 plasma treatments alter the CNW surface chemistry and wettability. • Cells seeded on CNW scaffolds are viable and metabolically active. • Surface functional groups, independent of surface wettability, affect cell response. • O2 plasma treatment of CNW leads to a more activated macrophage phenotype

  5. Bone Marrow Mononuclear Cell Transplantation Restores Inflammatory Balance of Cytokines after ST Segment Elevation Myocardial Infarction.

    Directory of Open Access Journals (Sweden)

    Kirsi Alestalo

    Full Text Available Acute myocardial infarction (AMI launches an inflammatory response and a repair process to compensate cardiac function. During this process, the balance between proinflammatory and anti-inflammatory cytokines is important for optimal cardiac repair. Stem cell transplantation after AMI improves tissue repair and increases the ventricular ejection fraction. Here, we studied in detail the acute effect of bone marrow mononuclear cell (BMMNC transplantation on proinflammatory and anti-inflammatory cytokines in patients with ST segment elevation myocardial infarction (STEMI.Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI were randomly assigned to receive either BMMNC or saline as an intracoronary injection. Cardiac function was evaluated by left ventricle angiogram during the PCI and again after 6 months. The concentrations of 27 cytokines were measured from plasma samples up to 4 days after the PCI and the intracoronary injection.Twenty-six patients (control group, n = 12; BMMNC group, n = 14 from the previously reported FINCELL study (n = 80 were included to this study. At day 2, the change in the proinflammatory cytokines correlated with the change in the anti-inflammatory cytokines in both groups (Kendall's tau, control 0.6; BMMNC 0.7. At day 4, the correlation had completely disappeared in the control group but was preserved in the BMMNC group (Kendall's tau, control 0.3; BMMNC 0.7.BMMNC transplantation is associated with preserved balance between pro- and anti-inflammatory cytokines after STEMI in PCI-treated patients. This may partly explain the favorable effect of stem cell transplantation after AMI.

  6. Differential DNA methylation regions in cytokine and transcription factor genomic loci associate with childhood physical aggression.

    Directory of Open Access Journals (Sweden)

    Nadine Provençal

    Full Text Available BACKGROUND: Animal and human studies suggest that inflammation is associated with behavioral disorders including aggression. We have recently shown that physical aggression of boys during childhood is strongly associated with reduced plasma levels of cytokines IL-1α, IL-4, IL-6, IL-8 and IL-10, later in early adulthood. This study tests the hypothesis that there is an association between differential DNA methylation regions in cytokine genes in T cells and monocytes DNA in adult subjects and a trajectory of physical aggression from childhood to adolescence. METHODOLOGY/PRINCIPAL FINDINGS: We compared the methylation profiles of the entire genomic loci encompassing the IL-1α, IL-6, IL-4, IL-10 and IL-8 and three of their regulatory transcription factors (TF NFkB1, NFAT5 and STAT6 genes in adult males on a chronic physical aggression trajectory (CPA and males with the same background who followed a normal physical aggression trajectory (control group from childhood to adolescence. We used the method of methylated DNA immunoprecipitation with comprehensive cytokine gene loci and TF loci microarray hybridization, statistical analysis and false discovery rate correction. We found differentially methylated regions to associate with CPA in both the cytokine loci as well as in their transcription factors loci analyzed. Some of these differentially methylated regions were located in known regulatory regions whereas others, to our knowledge, were previously unknown as regulatory areas. However, using the ENCODE database, we were able to identify key regulatory elements in many of these regions that indicate that they might be involved in the regulation of cytokine expression. CONCLUSIONS: We provide here the first evidence for an association between differential DNA methylation in cytokines and their regulators in T cells and monocytes and male physical aggression.

  7. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection.

    Science.gov (United States)

    Goodier, Martin R; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M; Darboe, Alansana; Moldoveanu, Ana L; White, Matthew J; Behrens, Ron; Riley, Eleanor M

    2016-07-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2-dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV(-)) individuals than in HCMV-seropositive (HCMV(+)) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV(+) and HCMV(-) subjects. In addition to these IL-2-dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57(-) NK cells and was most evident in HCMV(+) subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  8. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection

    Science.gov (United States)

    Goodier, Martin R.; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M.; Darboe, Alansana; Moldoveanu, Ana L.; White, Matthew J.; Behrens, Ron

    2016-01-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2–dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV−) individuals than in HCMV-seropositive (HCMV+) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV+ and HCMV− subjects. In addition to these IL-2–dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57− NK cells and was most evident in HCMV+ subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  9. Plasma properties

    International Nuclear Information System (INIS)

    The topics of active research in the calendar year 1989 included: RF induced plasma transport, not only for its effects on the mean particle distribution function but also as a means to enhance confinement of particles and to eliminate relatively cold alpha particle ash; thorough statistical analysis of tokamak data; improved neoclassical transport analysis; deeper analysis of two-fluid Braginskii transport in a tokamak; modelling of the plasma edge and wall interaction problem; reformulation of ballooning mode stability analysis in particularly strong and general terms; MHD modelling of tokamak phenomena, such as H-mode transition, and giant sawteeth, description of highly elongated tokamaks; and analysis of edge plasma RF antenna interactions. Our basic plasma physics studies include: statistical mechanics of Coulomb gases in bounded domains; theory of MHD instabilities with flow; numerical scheme for kinetic equations with nontrivial collision operators, and heat flow in particle simulations induced by discreteness effects. In addition, there is a modest space plasma physics effort funded by non-DOE sources. The studies of heating of the solar corona are strongly affected by work from the fusion program. Equally, work on ballooning modes led to work in magnetotail instabilities and additional solar corona heating mechanisms. We except to keep some research effort in this area. We do not include in this proposal plans for any new work in this field

  10. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qian-fei; Liu, Xin; O' Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L.; VandeBerg, John L.; Rubin, Edward M.; Cheng, Jan-Fang; Pennacchio, Len A.

    2003-09-15

    Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.

  11. Fish oil affects immune function in 9 to 12 month old infants

    DEFF Research Database (Denmark)

    Damsgaard, Camilla Trab; Lauritzen, Lotte; Kjær, Tanja;

    Background - n-3 Polyunsaturated fatty acids (PUFA) are thought to affect immune function and may affect immune maturation in early life. Objective - To examine if fish oil supplementation in late infancy could modify immune function. Design - A 2×2 intervention with fish oil (3.4 ± 1.1 ml/day) or...... no fish oil and cow’s milk or infant formula from 9 to 12 month of age in 64 healthy Danish infants. Before and after the intervention we measured the fatty acid composition of erythrocyte (RBC) membranes, plasma IgE levels, C-reactive protein and soluble IL-2 receptors (sIL-2R) as well as cytokine...

  12. Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury.

    Science.gov (United States)

    Helmy, Adel; Guilfoyle, Mathew R; Carpenter, Keri Lh; Pickard, John D; Menon, David K; Hutchinson, Peter J

    2016-08-01

    Interleukin-1 receptor antagonist (IL1ra) has demonstrated efficacy in a wide range of animal models of neuronal injury. We have previously published a randomised controlled study of IL1ra in human severe TBI, with concomitant microdialysis and plasma sampling of 42 cytokines and chemokines. In this study, we have used partial least squares discriminant analysis to model the effects of drug administration and time following injury on the cytokine milieu within the injured brain. We demonstrate that treatment with rhIL1ra causes a brain-specific modification of the cytokine and chemokine response to injury, particularly in samples from the first 48 h following injury. The magnitude of this response is dependent on the concentration of IL1ra achieved in the brain extracellular space. Chemokines related to recruitment of macrophages from the plasma compartment (MCP-1) and biasing towards a M1 microglial phenotype (GM-CSF, IL1) are increased in patient samples in the rhIL1ra-treated patients. In control patients, cytokines and chemokines biased to a M2 microglia phenotype (IL4, IL10, MDC) are relatively increased. This pattern of response suggests that a simple classification of IL1ra as an 'anti-inflammatory' cytokine may not be appropriate and highlights the importance of the microglial response to injury. PMID:26661249

  13. Protective effects of cytokines on bone marrow suppression by radioimmurotherapy in animal model

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Seiji [Ehime Univ., Shigenobu (Japan). School of Medicine

    1995-06-01

    In radioimmunotherapy, the dose limiting factor seems to be bone marrow suppression. Recombinant human granulocyte-colony stimulating factor (rhG-CSF), recombinant human erythropoietin (rhEPO), and recombinant human interleukin-6 (rhIL-6) are the hematopoietic growth factors which regulate the proliferation and differentiation of human bone marrow progenitor cell populations. We applied these cytokines to protect against bone marrow suppression induced by {sup 131}I-radioimmunotherapy in an animal model. Tumor (SCC-3: monocytic cell line)-bearing athymic mice were intraperitoneally injected with 13 MBq/35 {mu}g of {sup 131}I-labeled MoAb (YK-1: IgG1, Kappa). Three days after the injection, various cytokines were subcutaneously injected once a day for 15 days. In the control group, the peripheral blood cell counts decreased over the 20 days, but each cytokine shortened the period of cytopenia; rhG-CSF for granulocytes, rhEPO for erythrocytes, and rhIL-6 for platelets. The biodistribution of {sup 125}I-YK-1 was not changed by the various cytokines. Also, the growth of the tumor was not affected and the antitumor effect of {sup 131}I-YK-1 was not changed. Thus the application of cytokines for radioimmunotherapy was found to be effective in protecting against bone marrow suppression. (author).

  14. Multiple mechanisms of cytokine action in neurodegenerative and psychiatric states: neurochemical and molecular substrates.

    Science.gov (United States)

    Hayley, Shawn; Anisman, Hymie

    2005-01-01

    Neuroinflammatory processes appear to play a fundamental role in the pathology associated with a number of neurodegenerative and psychiatric conditions. In this respect, the immunocompetent brain microglia and peripheral macrophages release a host of proinflammatory cytokines that not only modulate immunological processes but also influence neuronal functioning and even survival. For instance, alterations of the cytokines, tumor necrosis factor-alpha, as well as several of the interferons and interleukins have been associated with Parkinson's disease (PD) and clinical depression. Importantly, anti-inflammatory treatments that block these cytokines may impart protection against behavioural pathology and neuronal damage in animal models of PD and depression involving exposure to environmental toxins and stressors, respectively. The present review highlights the involvement of inflammatory cells and cytokines in depression and PD and explores some of the potential cellular and molecular mechanisms through which the immunotransmitters affect neuronal functioning. Attention is also devoted to the possibility that cytokines may sensitize neuroinflammatory pathways that, in turn, favour long-term pathology. PMID:15777246

  15. Relation between Pro-inflammatory Cytokines and Acetylcholine Levels in Relapsing-Remitting Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Ada Maria Tata

    2012-10-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory, demyelinating and neurodegenerative disorder. Since acetylcholine (ACh is known to participate in the inflammatory response, we investigated the possible relationship between pro-inflammatory cytokines and acetylcholine levels in relapsing-remitting multiple sclerosis (RR-MS patients. Levels of ACh and pro-inflammatory cytokines IL1-β and IL-17 were measured both in cerebrospinal fluid (CSF and sera of 22 RR-MS patients in the relapsing phase and in 17 control subjects affected by other non-neurological diseases (OND. We observed higher levels of pro-inflammatory cytokines such as IL-1β and IL-17 in both CSF and serum of RR-MS patients compared to control subjects. Moreover, ACh levels were lower in CSF and serum of RR-MS patients compared to levels of control subjects. Although the relationship between high inflammatory cytokine levels and low ACh levels need to be further investigated in the future, our data suggest that IL-1β, and cytokines induced by it, such as IL-17 and ACh, may be involved in the pathogenesis of MS.

  16. Effect of Semen on Vaginal Fluid Cytokines and Secretory Leukocyte Protease Inhibitor

    Science.gov (United States)

    Agnew, Kathy J.; Aura, Jan; Nunez, Norma; Lee, Zandra; Lawler, Rick; Richardson, Carol E.; Culhane, Jennifer; Hitti, Jane

    2008-01-01

    The presence of semen in vaginal fluid, as identified by an acid phosphatase spot test, does not influence vaginal proinflammatory cytokine concentrations. Objective: determine whether semen, as detected by acid phosphatase, influences vaginal cytokines or secretory leukocyte protease inhibitor concentrations. Methods: 138 pregnant women had vaginal fluid collected for Gram stain, acid phosphatase detection by colorimetric assay, and interleukin 1-Beta, interleukin-6, interleukin-8, and secretory leukocyte protease inhibitor measurement by enzyme immunoassay. Results for women with and without acid phosphatase were compared by Mann-Whitney test. Results: of 138 subjects, 28 (20%) had acid phosphatase detected; of these, only 19 (68%) reported recent intercourse and 3 (11%) had sperm seen on Gram stain. There were no significant differences in proinflammatory cytokine concentrations; however, secretory leukocyte protease inhibitor concentrations were significantly higher among women with acid phosphatase. Conclusions: proinflammatory cytokine measurement does not appear to be affected by the presence of semen, but secretory leukocyte protease inhibitor is significantly higher when semen is present. Detection of semen by acid phosphatase was associated with higher vaginal SLPI concentrations, however, the presence of semen did not appear to influence vaginal proinflammatory cytokine concentrations. PMID:18615190

  17. Effect of Semen on Vaginal Fluid Cytokines and Secretory Leukocyte Protease Inhibitor

    Directory of Open Access Journals (Sweden)

    Jane Hitti

    2008-07-01

    Full Text Available The presence of semen in vaginal fluid, as identified by an acid phosphatase spot test, does not influence vaginal proinflammatory cytokine concentrations. Objective: determine whether semen, as detected by acid phosphatase, influences vaginal cytokines or secretory leukocyte protease inhibitor concentrations. Methods: 138 pregnant women had vaginal fluid collected for Gram stain, acid phosphatase detection by colorimetric assay, and interleukin 1-Beta, interleukin-6, interleukin-8, and secretory leukocyte protease inhibitor measurement by enzyme immunoassay. Results for women with and without acid phosphatase were compared by Mann-Whitney test. Results: of 138 subjects, 28 (20% had acid phosphatase detected; of these, only 19 (68% reported recent intercourse and 3 (11% had sperm seen on Gram stain. There were no significant differences in proinflammatory cytokine concentrations; however, secretory leukocyte protease inhibitor concentrations were significantly higher among women with acid phosphatase. Conclusions: proinflammatory cytokine measurement does not appear to be affected by the presence of semen, but secretory leukocyte protease inhibitor is significantly higher when semen is present. Detection of semen by acid phosphatase was associated with higher vaginal SLPI concentrations, however, the presence of semen did not appear to influence vaginal proinflammatory cytokine concentrations.

  18. Heroin use is associated with suppressed pro-inflammatory cytokine response after LPS exposure in HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Hinta Meijerink

    Full Text Available Opioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens.Treatment naïve HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1 using heroin 2 receiving methadone opioid substitution 3 using heroin over 1 year ago and 4 controls (never used opioids. Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 β, IL-6, IL-10, IFN-α, IFN-γ and TNF-α was determined using multiplex beads assay.Among 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p<0.05. After stimulation with either M. tuberculosis or C. albicans the cytokine production of all groups were comparable.The cytokine production after exposure to LPS is significantly down-regulated in HIV-infected heroin users. Interesting, methadone use did not suppress cytokine response, which could have implications guidelines of opioid substitution.

  19. Abnormal gene expression of proinflammatory cytokines and their membrane-bound receptors in the lymphocytes of depressed patients.

    Science.gov (United States)

    Rizavi, Hooriyah S; Ren, Xinguo; Zhang, Hui; Bhaumik, Runa; Pandey, Ghanshyam N

    2016-06-30

    Abnormalities of protein levels of proinflammatory cytokines and their soluble receptors have been reported in plasma of depressed patients. In this study, we examined the role of cytokines and their membrane-bound receptors in major depressive disorder (MDD). We determined the protein and mRNA expression of proinflammatory cytokines, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and mRNA expression of their membrane-bound receptors in the lymphocytes from 31 hospitalized MDD patients and 30 non-hospitalized normal control (NC) subjects. The subjects were diagnosed according to DSM-IV criteria. Protein levels of cytokines were determined by ELISA, and mRNA levels in lymphocytes were determined by the qPCR method. We found that the mean mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNF-α, their receptors, TNFR1, TNFR2, IL-1R1 and the antagonist IL-1RA were significantly increased in the lymphocytes of MDD patients compared with NC. No significant differences in the lymphocyte mRNA levels of IL-1R2, IL-6R, and Gp130 were observed between MDD patients and NC. These studies suggest abnormal gene expression of these cytokines and their membrane-bound receptors in the lymphocytes of MDD patients, and that their mRNA expression levels in the lymphocytes could be a useful biomarker for depression. PMID:27138824

  20. Changes in serum cytokines in response to musculoskeletal surgical trauma

    OpenAIRE

    Reikeras, Olav; Borgen, Pål; Reseland, Janne E; Lyngstadaas, Staale P

    2014-01-01

    Background Trauma induces local and subsequent systemic inflammatory reactions, and when the cytokine production is deregulated, a systemic inflammatory response syndrome with a potentially lethal outcome can occur. The understanding of the physiological mechanism of the cytokine network would be useful to better comprehend pathological conditions. Methods We analysed a panel of 30 cytokines in the serum of 20 patients operated with total hip replacement. Cytokine release was assessed postope...

  1. Mechanism of cytokine modulation of epithelial tight junction barrier

    OpenAIRE

    Al-Sadi, Rana; Boivin, Michel; Ma, Thomas

    2009-01-01

    Cytokines play a crucial role in the modulation of inflammatory response in the gastrointestinal tract. Pro-inflammatory cytokines including tumor necrosis factor-α, interferon-γ, interleukin-1β (IL-1β), and interleukin-12 are essential in mediating the inflammatory response, while anti-inflammatory cytokines including interleukin-10 and transforming growth factor-β are important in the attenuation or containment of inflammatory process. It is increasingly recognized that cytokines have an im...

  2. THE EFFECTS OF COMBINATORIAL EXPOSURE OF PRO-INFLAMMATORY AND ANTI-INFLAMMATORY CYTOKINES ON AIRWAY EPITHELIAL CELL RELEASE OF CHEMOTACTIC MEDIATORS

    Science.gov (United States)

    Asthma is a chronic inflammatory disorder of the airways affecting nearly 15 million individuals nationally. Within the inflamed asthmatic airway there exist complex interactions between many cells and the cytokines they release, in particular mast cells, eosinophils, T-lymphocy...

  3. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines.

    Science.gov (United States)

    Warrington, Junie P

    2015-11-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ~13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R(2) = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  4. Alteration of cytokine profile following hemorrhagic shock.

    Science.gov (United States)

    Lu, Sumin; Aguilar, Alex; Subramani, Kumar; Poulose, Ninu; Ayub, Ahmar; Raju, Raghavan

    2016-05-01

    Hemorrhage is one of the leading causes of death in patients with trauma. We recently demonstrated that resveratrol can improve cardiac function and prolong life following severe hemorrhagic injury (HI) in a rat model. The present work is focused on determining changes in NF-κB dependent gene expression in the heart and the systemic cytokine milieu following HI and the effect of resveratrol treatment. The results indicate an increase in phosphorylated NF-κB in the heart with a concomitant increase in the expression of NF-κB dependent genes following HI. There was also a significant increase of systemic cytokine levels, both pro and anti-inflammatory, following HI and resolution when treated with resveratrol. This study demonstrates the potential role NF-κB has in the physiological response to HI and the effectiveness of resveratrol in reducing immune activation. PMID:26851979

  5. Cytokines and Organ Failure in Acute Pancreatitis

    DEFF Research Database (Denmark)

    Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller;

    2012-01-01

    Objectives: We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP). Methods: Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor > were measured on admission and...... at days 1, 2, and 14 in 60 patients admitted with first attack of AP. The prediction of single-organ and multiorgan failure from the cytokine profiles was evaluated by receiver operating characteristic analyses. Results: Interleukin 6 and IL-8 levels were significantly higher in patients who...... developed renal, respiratory, and circulatory failure, as was the case for patients with multiorgan failure. Interleukin 18 levels were significantly elevated in renal and respiratory failure only. Tumor necrosis factor > was significantly elevated in all types of organ failures, except for intestinal...

  6. Cytokine Expression in Homozygous Sickle Cell Anaemia

    Directory of Open Access Journals (Sweden)

    Nnodim Johnkennedy

    2015-01-01

    Full Text Available Background: Sickle cell anaemia is an inherited disease in which the red blood cells become rigid and sticky, and change from being disc-shaped to being crescent-shaped. The change in shape is due to the presence of an abnormal form of haemoglobin. This results in severe pain and damage to some organs. Aim and Objective: The study was carried out to determine the levels of cytokine in sickle cell anemia. Material and Methods: Thirty confirmed sickle cell patients in steady state (HbSS-SS and thirty persons with normal haemoglobin (HbAA as well as sixteen sickle cell disease in crises (HbSS-cr between the ages of 15 to 30 years were selected in this study. Cytokines including interleukin 1 beta (IL- 1β, interleukin 2 (IL- 2, interleukin (IL-6, tumour necrosis factor alpha (TNF-α, and interferon gamma (IFN- λ were measured by commercially available ELISA kits. Results: The results obtained showed that the levels of TNF-α and IL-6 in sickle cell anaemia patients in crisis were significantly elevated when compared with sickle cell in steady state (P<0.05. Similarly, the levels of IL-1β, IL-6, and IFN- λ were significantly increased in sickle cell anaemia stable state when compared to HbAA subjects (P<0.05. Conclusion: This may probably implies that cytokine imbalance is implicated in the pathogenesis of sickle cell crisis. Also, cytokines could be used as an inflammatory marker as well as related marker in disease severity and hence therapeutic intervention.

  7. The Role of Cytokines in Sleep Regulation

    OpenAIRE

    Krueger, James M.

    2008-01-01

    Interleukin-1 beta (IL1) and tumor necrosis factor alpha (TNF) promote non-rapid eye movement sleep under physiological and inflammatory conditions. Additional cytokines are also likely involved but evidence is insufficient to conclude that they are sleep regulatory substances. Many of the symptoms induced by sleep loss, e.g. sleepiness, fatigue, poor cognition, enhanced sensitivity to pain, can be elicited by injection of exogenous IL1 or TNF. We propose that ATP, released during neurotransm...

  8. Proteolytic inactivation of cytokines by Pseudomonas aeruginosa.

    OpenAIRE

    Parmely, M; Gale, A; Clabaugh, M.; Horvat, R; Zhou, W W

    1990-01-01

    Pseudomonas aeruginosa alkaline protease and elastase are thought to contribute to bacterial invasiveness, tissue damage, and immune suppression in animals and patients infected with the bacterium. This study examined the ability of the two proteases to inactivate a number of cytokines that mediate immune and inflammatory responses. Human recombinant gamma interferon (rIFN-gamma) and human recombinant tumor necrosis factor alpha were inactivated by both proteases. Murine rIFN-gamma was relati...

  9. Cytokine orchestration in post-operative peritoneal adhesion formation

    Institute of Scientific and Technical Information of China (English)

    Ronan A Cahill; H Paul Redmond

    2008-01-01

    Peritoneal adhesions are a near inevitable occurrence after laparotomy and a major cause of both patient and physician misery.To date,clinical attempts at their amelioration have concentrated on manipulating the physical factors that affect their development despite a wealth of experimental data elucidating the molecular mechanisms that underlie their initiation,development and maturation.However,the advent of targeted,specific anti-cytokine agents as directed therapy for inflammatory and neoplastic conditions raises the prospect of a new era for anti-adhesion strategies.To harness this potential will require considerable cross-disciplinary collaboration and that surgeon-scientists propel themselves to the forefront of this emerging field.

  10. Diagnosis of uterine and vaginal disorders by different methodologies is affected by concentration of estradiol in plasma from lactating Holstein cows.

    Science.gov (United States)

    Silper, B F; Madureira, A M L; Burnett, T A; Fernandes, A C C; Abreu, F M; Veira, D M; Vasconcelos, J L M; Cerri, R L A

    2016-06-01

    The relationship between plasma estradiol concentration at time of examination and prevalence of uterine disorders, agreement among methods, and associations of diagnosis with pregnancy hazard and milk yield was studied in 268 Holstein cows examined at 30±3 (exam 1) and 44±3 d in milk (DIM; exam 2). Purulent vaginal discharge was sampled using 2 methods: gloved hand and Metricheck (Simcro, Hamilton, New Zealand; PVD; score ≥3). Percentage of polymorphonuclear leukocytes was determined by endometrial cytology (CYTO; exam 1: ≥18%, exam 2: ≥10%); diameter of uterine horns (UTH; >20 mm), diameter of the inner layer of the cervix (CVX; >20.5 mm), presence of fluid in the uterine lumen (FL), and ovarian structures were evaluated by ultrasonography. A blood sample was collected at each exam for estradiol analysis. Prevalence at exams 1 and 2 was, respectively, 14.2 and 18.5% (PVD), 21.4 and 10.1% (FL), and 40.6 and 50.2% (CYTO). Prevalence of PVD at exam 1 was greater among cows with estradiol ≥2 pg/mL (19.4 vs. 8.2%). Agreement of all methods with CYTO was poor, the greatest being between CYTO and FL (exam 1; kappa=0.19). Agreement between CYTO and PVD, and between CYTO and FL (exam 1; kappa=0.15 and 0.35, respectively) was higher among cows with estradiol ≥2 pg/mL. Likelihood of PVD at exam 1 was greater if cows were positive for CVX [odds ratio (OR)=3.0], FL (OR=2.6) or had estradiol ≥2 pg/mL (OR=2.7). Likelihood of CYTO increased with dystocia (OR=2.3) and FL (OR=2.5). Estradiol did not influence diagnosis at exam 2. Positive FL or CYTO at exam 1 was associated with reductions in milk yield of 59 to 180 kg by 45 DIM. Pregnancy hazard until 250 DIM was reduced by CYTO at exam 1 (hazard ratio=0.74) and by PVD (hazard ratio=0.68) at exam 2. However, FL and CYTO reduced pregnancy hazard only when estradiol was ≥2 pg/mL (exam 1), whereas PVD reduced pregnancy hazard when diagnosed at exam 2 with estradiol <2 pg/mL. Overall, agreement was poor and effects of

  11. Plasma properties

    International Nuclear Information System (INIS)

    A cursory examination of the research activities of the Magneto-Fluid Dynamics Division for the calendar year 1988 shows the effects of the gradual transformation of the group. Although our principal activity, fusion plasma physics research, is unchanged, the work shows closer ties to problems relevant to present experiments than previously. Most notable is the concentrated effort on tokamak equilibrium and transport. We are exploring the implication of turbulence induced transport, resistive MHD effects, neoclassical transport, and possible interpretations of transport based on classical phenomena. In addition, one of our members has chosen to focus on problems of enhanced statistical methods for interpretation of experiments. All of this activity preceded the Tokamak Transport Initiative and reflects our active involvement and concern with the world-wide tokamak program. Since equilibrium and transport are by no means the only theoretical plasma physics problems affecting fusion devices we continue substantial efforts in wave propagation and heating, particle simulation of plasmas, stability theory, enhancement of numerical algorithms, and general plasma physics. We are attempting to develop effective numerical schemes for the Boltzmann equation, adaptive grid methods for MHD, and particle simulation of boundary and antenna effects. Many of these topics reflect our continuing concern to maintain a modest effort in the development of theoretical models and tools for problems of real significance to fusion, but not necessarily of immediate highest priority. We select problems which we expect to become extremely important in the future. Our space plasma physics activities, funded by agencies other than DOE, transfers knowledge learned in fusion plasma physics to another area and conversely stimulates work also relevant to fusion problems

  12. Magnetic resonance imaging determined visceral fat reduction associates with enhanced IL-10 plasma levels in calorie restricted obese subjects.

    Directory of Open Access Journals (Sweden)

    Gloria Formoso

    Full Text Available BACKGROUND: Obesity is characterized by a low grade chronic inflammation state. Indeed circulating pro-inflammatory cytokines, such as TNF-α and IL-6, are elevated in obese subjects, while anti-inflammatory cytokines, such as IL-10, appear to be reduced. Cytokines profile improves after weight loss, but how visceral or subcutaneous fat loss respectively affect pro- or anti-inflammatory cytokines plasma levels has not been precisely assessed. Therefore in the present study we correlated changes in circulating cytokine profile with quantitative changes in visceral and subcutaneous adipose tissue depots measured by an ad hoc Magnetic Resonance Imaging (MRI protocol before and after weight loss. MATERIALS AND METHODS: In 14 obese subjects, MRI determination of visceral and subcutaneous fat and plasma glucose, insulin, TNF-α IL-6, and IL-10 measurements were performed before and after a caloric restriction induced weight loss of at least 5% of the original body weight. RESULTS: Weight loss improved insulin sensitivity (QUICKI Index: 0.35±0.03 vs 0.37±0.04; P<0.05, increased IL-10 (3.4±1.9 vs 4.6±1.0 pg/mL; P<0.03, and reduced TNF-α and IL-6 plasma levels (2.5±1.3 vs 1.6±1.5 pg/mL, P<0.0015, 2.3±0.4 vs 1.6±0.6 pg/mL, P<0.02 respectively. A significant correlation was observed between the amount of visceral fat loss and the percentage reduction in both TNF-α (r = 0.56, p<0.05 and IL-6 (r = 0.19 p<0.05 plasma levels. In a multiple regression analysis, the amount of visceral fat loss independently correlated with the increase in IL-10 plasma levels. CONCLUSION: The reduction in visceral adipose tissue is the main driver of the improved inflammatory profile induced by weight loss.

  13. Effect of acetazolamide on cytokines in rats exposed to high altitude.

    Science.gov (United States)

    Wang, Chang; Wang, Rong; Xie, Hua; Sun, Yuhuan; Tao, Rui; Liu, Wenqing; Li, Wenbin; Lu, Hui; Jia, Zhengping

    2016-07-01

    Acute mountain sickness (AMS) is a dangerous hypoxic illness that can affect humans who rapidly reach a high altitude above 2500m. In the study, we investigated the changes of cytokines induced by plateau, and the acetazolamide (ACZ) influenced the cytokines in rats exposed to high altitude. Wistar rats were divided into low altitude (Control), high altitude (HA), and high altitude+ACZ (22.33mg/kg, Bid) (HA+ACZ) group. The rats were acute exposed to high altitude at 4300m for 3days. The HA+ACZ group were given ACZ by intragastric administration. The placebo was equal volume saline. The results showed that hypoxia caused the heart, liver and lung damage, compared with the control group. Supplementation with ACZ significantly alleviated hypoxia-caused damage to the main organs. Compared with the HA group, the biochemical and blood gas indicators of the HA+ACZ group showed no difference, while some cytokines have significantly changed, such as activin A, intercellular adhesion molecule-1 (ICAM-1, CD54), interleukin-1α,2 (IL-1α,2), l-selectin, monocyte chemotactic factor (MCP-1), CC chemokines (MIP-3α) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). Then, the significant difference pro-inflammatory cytokines in protein array were chosen for further research. The protein and mRNA content of pro-inflammatory cytokines MCP-1, interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), interferon-γ (IFN-γ) in rat lung were detected. The results demonstrated that the high altitude affected the body's physiological and biochemical parameters, but, ACZ did not change those parameters of the hypoxia rats. This study found that ACZ could decrease the content of pro-inflammatory cytokines, such as MCP-1, IL-1β, TNF-α and IFN-γ in rat lungs, and, the lung injury in the HA+ACZ group reduced. The mechanism that ACZ protected hypoxia rats might be related to changes in cytokine content. The reducing of the pro-inflammatory cytokines in rat lung might be other

  14. Activation of monocytes and cytokine production in patients with peripheral atherosclerosis obliterans

    Directory of Open Access Journals (Sweden)

    Lastória Sidney

    2011-08-01

    Full Text Available Abstract Background Arterial peripheral disease is a condition caused by the blocked blood flow resulting from arterial cholesterol deposits within the arms, legs and aorta. Studies have shown that macrophages in atherosclerotic plaque are highly activated, which makes these cells important antigen-presenting cells that develop a specific immune response, in which LDLox is the inducing antigen. As functional changes of cells which participate in the atherogenesis process may occur in the peripheral blood, the objectives of the present study were to evaluate plasma levels of anti-inflammatory and inflammatory cytokines including TNF-α, IFN-γ, interleukin-6 (IL-6, IL-10 and TGF-β in patients with peripheral arteriosclerosis obliterans, to assess the monocyte activation level in peripheral blood through the ability of these cells to release hydrogen peroxide (H2O2 and to develop fungicidal activity against Candida albicans (C. albicans in vitro. Methods TNF-α, IFN-γ, IL-6, IL-10 and TGF-β from plasma of patients were detected by ELISA. Monocyte cultures activated in vitro with TNF-alpha and IFN-gamma were evaluated by fungicidal activity against C. albicans by culture plating and Colony Forming Unit (CFU recovery, and by H2O2 production. Results Plasma levels of all cytokines were significantly higher in patients compared to those detected in control subjects. Control group monocytes did not release substantial levels of H2O2 in vitro, but these levels were significantly increased after activation with IFN-γ and TNF-α. Monocytes of patients, before and after activation, responded less than those of control subjects. Similar results were found when fungicidal activity was evaluated. The results seen in patients were always significantly smaller than among control subjects. Conclusions: The results revealed an unresponsiveness of patient monocytes in vitro probably due to the high activation process occurring in vivo as corroborated by high

  15. Regulation of cytokines by small RNAs during skin inflammation

    Directory of Open Access Journals (Sweden)

    Mikkelsen Jacob G

    2010-07-01

    Full Text Available Abstract Intercellular signaling by cytokines is a vital feature of the innate immune system. In skin, an inflammatory response is mediated by cytokines and an entwined network of cellular communication between T-cells and epidermal keratinocytes. Dysregulated cytokine production, orchestrated by activated T-cells homing to the skin, is believed to be the main cause of psoriasis, a common inflammatory skin disorder. Cytokines are heavily regulated at the transcriptional level, but emerging evidence suggests that regulatory mechanisms that operate after transcription play a key role in balancing the production of cytokines. Herein, we review the nature of cytokine signaling in psoriasis with particular emphasis on regulation by mRNA destabilizing elements and the potential targeting of cytokine-encoding mRNAs by miRNAs. The proposed linkage between mRNA decay mediated by AU-rich elements and miRNA association is described and discussed as a possible general feature of cytokine regulation in skin. Moreover, we describe the latest attempts to therapeutically target cytokines at the RNA level in psoriasis by exploiting the cellular RNA interference machinery. The applicability of cytokine-encoding mRNAs as future clinical drug targets is evaluated, and advances and obstacles related to topical administration of RNA-based drugs targeting the cytokine circuit in psoriasis are described.

  16. How does Chinese medicine target cytokine imbalance in rheumatoid arthritis?

    Science.gov (United States)

    Liu, Jian; Sun, Yue

    2013-11-01

    Rheumatoid arthritis (RA) manifests as an imbalance between pro- and anti-inflammatory cytokines. Cytokine imbalance is suggested to play critical roles in the development of RA. Currently, various treatments for RA, including biological agents such as antibodies against inflammation mediators, or Chinese herbal medicines, intervene the disease by restoring the balance of cytokines. Chinese medicine (CM) can not only suppress the expression of pro-inflammatory cytokines, but also induce the expression of cytokines with anti-inflammatory and immunomodulatory effects. Thus, Chinese medicine can effectively reduce inflammatory cell infiltration into synovial tissue, pannus formation, and degradation of the extracellular matrix surrounding cartilage cells, thereby reducing subchondral bone damage. This paper reviews the changes of cytokine profiling during development of RA and discuss the mechanisms by which Chinese medicine restores the cytokine balance. PMID:24170633

  17. Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.;

    1999-01-01

    Ageing is associated with decreased resistance to bacterial infections and concomitant increased circulating levels of inflammatory cytokines. The purpose of the present study was to research age-related changes in levels of early mediators of the acute-phase response in whole blood supernatants...... following LPS stimulation, representing an ex vivo model of sepsis. Levels of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6 in whole blood supernatants were measured after in vitro LPS stimulation for 24 h in 168 elderly humans aged 81 years from the 1914 cohort in Glostrup, Denmark and in 91...... proinflammatory cytokines compared with young men, but this difference was blurred by ageing. No relation was found between circulating plasma levels of TNF-alpha and levels after in vitro LPS stimulation. In conclusion, decreased production of TNF-alpha and IL-1 beta after exposure to LPS may reflect impaired...

  18. Waves in unmagnetized plasma

    International Nuclear Information System (INIS)

    A review of linear and weakly non-linear theory of electron waves, ion waves and electromagnetic waves in plasmas is presented. The author restricts the discussion to an infinitely extended, homogeneous and isotropic plasma, not affected by external fields and described by Vlasov's and Maxwell's equations. (Auth.)

  19. Environmental mold and mycotoxin exposures elicit specific cytokine and chemokine responses.

    Directory of Open Access Journals (Sweden)

    Jamie H Rosenblum Lichtenstein

    Full Text Available Molds can cause respiratory symptoms and asthma. We sought to use isolated peripheral blood mononuclear cells (PBMCs to understand changes in cytokine and chemokine levels in response to mold and mycotoxin exposures and to link these levels with respiratory symptoms in humans. We did this by utilizing an ex vivo assay approach to differentiate mold-exposed patients and unexposed controls. While circulating plasma chemokine and cytokine levels from these two groups might be similar, we hypothesized that by challenging their isolated white blood cells with mold or mold extracts, we would see a differential chemokine and cytokine release.Peripheral blood mononuclear cells (PBMCs were isolated from blood from 33 patients with a history of mold exposures and from 17 controls. Cultured PBMCs were incubated with the most prominent Stachybotrys chartarum mycotoxin, satratoxin G, or with aqueous mold extract, ionomycin, or media, each with or without PMA. Additional PBMCs were exposed to spores of Aspergillus niger, Cladosporium herbarum and Penicillium chrysogenum. After 18 hours, cytokines and chemokines released into the culture medium were measured by multiplex assay. Clinical histories, physical examinations and pulmonary function tests were also conducted. After ex vivo PBMC exposures to molds or mycotoxins, the chemokine and cytokine profiles from patients with a history of mold exposure were significantly different from those of unexposed controls. In contrast, biomarker profiles from cells exposed to media alone showed no difference between the patients and controls.These findings demonstrate that chronic mold exposures induced changes in inflammatory and immune system responses to specific mold and mycotoxin challenges. These responses can differentiate mold-exposed patients from unexposed controls. This strategy may be a powerful approach to document immune system responsiveness to molds and other inflammation-inducing environmental agents.

  20. Temporal Cytokine Profiles in Severely Burned Patients: A Comparison of Adults and Children

    Science.gov (United States)

    Finnerty, Celeste C; Jeschke, Marc G; Herndon, David N; Gamelli, Richard; Gibran, Nicole; Klein, Matthew; Silver, Geoff; Arnoldo, Brett; Remick, Daniel; Tompkins, Ronald G

    2008-01-01

    A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structural changes of essential organs. The release of cytokines has been implicated in this hypermetabolic response. The severity of the hypermetabolic response following burn injury increases with age, as does the mortality rate. Due to the relationship between the hypermetabolic and inflammatory responses, we sought to compare the plasma cytokine profiles following a severe burn in adults and in children. We enrolled 25 adults and 24 children who survived a flame burn covering more than 20% of total body surface area (TBSA). The concentrations of 22 cytokines were measured using the Linco multiplex array system (St. Charles, MO, USA). Large perturbations in the expression of pro- and anti-inflammatory cytokines were seen following thermal injury. During the first week following burn injury, IFN-γ, IL-10, IL-17, IL-4, IL-6, and IL-8 were detected at significantly higher levels in adults compared with children, P < 0.05. Significant differences were measured during the second week post-burn for IL-1β (higher in children) and IL-5 (higher in adults), P < 0.05. IL-18 was more abundant in children compared with adults during the third week post-burn, P < 0.05. Between post-burn d 21 and d 66, IL-1α was detected at higher concentrations in pediatric compared with adult patients, P < 0.05. Only GM-CSF expression was significantly different at all time points; it was detected at lower levels in pediatric patients, P < 0.05. Eotaxin, G-CSF, IL-13, IL-15, IP-10, MCP-1, and MIP-1α were detected at significantly different concentrations in adult compared with pediatric patients at multiple time points, P < 0.05. There were no differences in IL-12, IL-2, IL-7, or TNF levels in adult compared with pediatric burn patients at any of these time points. Following severe flame burns, the cytokine profiles in pediatric patients differ compared with those in adult patients, which may

  1. Forecasting Cytokine Storms with New Predictive Biomarkers.

    Science.gov (United States)

    Rouce, Rayne H; Heslop, Helen E

    2016-06-01

    T cells genetically modified with CD19 chimeric antigen receptors have produced impressive clinical responses in patients with refractory B-cell malignancies, but therapeutic responses are often accompanied by cytokine release syndrome (CRS), which can cause significant morbidity and mortality. Teachey and colleagues have identified predictive biomarkers for this complication that may allow testing of earlier intervention with agents such as the IL6 receptor blocker tocilizumab to evaluate whether CRS can be ameliorated without jeopardizing clinical responses. Cancer Discov; 6(6); 579-80. ©2016 AACR.See related article by Teachey et al., p. 664. PMID:27261481

  2. Cytokines in the modulation of eosinophilia

    Directory of Open Access Journals (Sweden)

    Faccioli Lúcia H

    1997-01-01

    Full Text Available In this review we discuss our recently results showing interleukin 5 (IL-5 involvement in eosinophil migration and in the maintenance of eosinophilia in blood, bone marrow, lung and peritoneal cavity, in a visceral larva migrans syndrome model using guinea-pigs infected with Toxocara canis. We also describe the sequential release of TNF-alpha and IL-8 during the course of infection, and the interaction between these cytokines and IL-5 during infection. Finally we propose a new biological role for IL-5, at least in our model, as a modulator of IL-8 release and secretion.

  3. Minocycline mitigates the gliogenic effects of proinflammatory cytokines on neural stem cells.

    Science.gov (United States)

    Vay, Sabine Ulrike; Blaschke, Stefan; Klein, Rebecca; Fink, Gereon Rudolf; Schroeter, Michael; Rueger, Maria Adele

    2016-02-01

    Mobilizing endogenous neural stem cells (NSCs) in the adult brain is designed to enhance the brain's regenerative capacity after cerebral lesions, e.g., as a result of stroke. Cerebral ischemia elicits neuroinflammatory processes affecting NSCs in multiple ways, the precise mechanisms of which currently remain elusive. An inhibitory effect of minocycline on microglia activation, a hallmark of postischemic neuroinflammation, has already been demonstrated in clinical trials, showing minocycline to be safe and potentially effective in ischemic stroke. Here we investigate the direct effects of minocycline and of proinflammatory cytokines on the differentiation potential of NSCs in vitro and in vivo. Primary fetal rat NSCs were treated with minocycline plus a combination of the proinflammatory cytokines tumor necrosis factor-α, interleukin 1β, and interleukin 6. The differentiation fate of NSCs was assessed immunocytochemically. To investigate the effects of minocycline and inflammation in vivo, minocycline or lipopolysaccharides were injected intraperitoneally into adult rats, with subsequent immunohistochemistry. Minocycline alone did not affect the differentiation potential of NSCs in vivo or in vitro. In contrast, proinflammatory cytokines accelerated the differentiation of NSCs, promoting an astrocytic fate while inhibiting neurogenesis in vitro and in vivo. It is interesting to note that minocycline counteracted this cytokine-induced rapid astrocytic differentiation and restored the neurogenic and oligodendrogliogenic potential of NSCs. Data suggest that minocycline antagonizes the rapid glial differentiation induced by proinflammatory cytokines following cerebral ischemia but without having a direct effect on the differentiation potential of NSCs. Thus, minocycline constitutes a promising drug for stroke research, counteracting the detrimental effects of postischemic neuroinflammation in multiple ways. PMID:26525774

  4. Plasma theory

    International Nuclear Information System (INIS)

    A series of lectures on plasma theory with the main headings: introduction; charged particles moving in em fields; the liquid model; transport phenomena in the plasma; wave propagation in plasmas; plasma instabilities. 57 figs. (qui)

  5. Understanding stress-induced immunosuppression: exploration of cytokine and chemokine gene profiles in chicken peripheral leukocytes.

    Science.gov (United States)

    Shini, S; Huff, G R; Shini, A; Kaiser, P

    2010-04-01

    that the delayed effects of chronic stress can suppress the immune response. Messenger RNA expression levels of transforming growth factor-beta4 (TGF-beta4) are also upregulated in cortisosterone-treated birds. It appears that the balance between T-helper (Th) 1 and Th2/T regulatory cytokine production is altered in conditions associated with significant changes in plasma corticosterone concentration. Experiments are underway to decipher the cytokine and chemokine responses to vaccination and bacterial challenge on the background of stress-induced immunosuppression. PMID:20308420

  6. Cytokine expression during syphilis infection in HIV-1-infected individuals

    DEFF Research Database (Denmark)

    Knudsen, Andreas; Benfield, Thomas; Kofoed, Kristian

    2009-01-01

    BACKGROUND: Little is known about cytokine responses to syphilis infection in HIV-1-infected individuals. METHODS: We retrospectively identified patients with HIV-1 and Treponema pallidum coinfection. Plasma samples from before, during, and after coinfection were analyzed for interleukin (IL)-2, IL......-4, IL-6, IL-8, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha. RESULTS: Thirty-six patients were included. IL-10 levels increased significantly in patients with primary or secondary stage syphilis from a median of 12.8 pg/mL [interquartile range (IQR), 11.0-27.8] before...... infection to 46.7 pg/mL (IQR, 28.4-78.9) at the time of diagnosis (P = 0.027) and decreased to 13.0 pg/mL (IQR, 6.2-19.4) after treatment of syphilis (P <0.001). TNF-alpha levels showed no significant change from before to during syphilis in patients with primary or secondary stage syphilis (median 3.9 pg...

  7. Specific siRNA Downregulated TLR9 and Altered Cytokine Expression Pattern in Macrophage after CpG DNA Stimulation

    Institute of Scientific and Technical Information of China (English)

    Bin Qiao; Baohua Li; Xiuli Yang; Hongyong Zhang; Yiwei Chu; Ying Wang; Sidong Xiong

    2005-01-01

    Bacterial CpG DNA or synthetic oligonucleotides (ODNs) that contain unmethylated CpG motifs (CpG ODN) can directly activate antigen-presenting cells (APCs) to secrete various cytokines through the intracellular receptor TLR9. Cytokine profiles elicited by the actions of stimulatory CpG DNA on TLR9 expressed APCs are crucial to the subsequent immune responses. To date, cytokine profiles in APCs upon CpG ODN stimulation in vitro are not fully investigated. In the present study, vector-based siRNA was used to downregulate TLR9 expression. Cytokine profiles were observed in murine macrophage cell line RAW264.7 transfected with TLR9-siRNA plasmid upon CpG ODN stimulation. We found that not all the cytokine expressions by the macrophage were decreased while TLR9 was downregulated. IL-12, TNF-α, IFN-γ and IL-1β expressions were significantly decreased, but IL-6,IFN-β and IL-10 expressions were not affected. Interestingly, the level of IFN-α was even increased. This alteration of cytokines produced by TLR9-downregulated APCs upon CpG ODN stimulation might indicate that the role of CpG DNA is more complicated in the pathogenesis and prevention of diseases. Cellular & Molecular Immunology.2005;2(2):130-135.

  8. Specific siRNA Downregulated TLR9 and Altered Cytokine Expression Pattern in Macrophage after CpG DNA Stimulation

    Institute of Scientific and Technical Information of China (English)

    BinQiao; BaohuaLi; XiuliYang; HongyongZhang; YiweiChu; YingWang; SidongXiong

    2005-01-01

    Bacterial CpG DNA or synthetic oligonucleotides (ODNs) that contain unmethylated CpG motifs (CpG ODN) can directly activate antigen-presenting cells (APCs) to secrete various cytokines through the intraceilular receptor TL R9. Cytokine profiles elicited by the actions of stimulatory CpG DNA on TLR9 expressed APCs are crucial to the subsequent immune responses. To date, cytokine profiles in APCs upon CpG ODN stimulation in vitro are not fully investigated. In the present study, vector-based siRNA was used to downregulate TLR9 expression. Cytokine profiles were observed in murine macrophage cell line RAW264.7 transfected with TLR9-siRNA plasmid uponCpG ODN stimulation. We found that not all the cytokine expressions by the macrophage were decreased whileTLR9 was downregulated. IL-12, TNF-α, IFN-γ and IL-1β expressions were significantly decreased, but IL-6, IFN-β and IL-10 expressions were not affected. Interestingly, the level of IFN-α was even increased. This alteration of cytokines produced by TLR9-downregulated APCs upon CpG ODN stimulation might indicate that the role of CpG DNA is more complicated in the pathogenesis and prevention of diseases. Cellular & Molecular Immunology. 2005;2(2):130-135.

  9. ACUTE PHASE PROTEINS, LIPID PROFILE AND PROINFLAMMATORY CYTOKINES IN HEALTHY AND BRONCHOPNEUMONIC WATER BUFFALO CALVES

    OpenAIRE

    El-Bahr, Sabry M.; Wael M. EL-Deeb

    2013-01-01

    The aim of the present study was to evaluate the diagnostic value of Acute Phase Proteins (APP), lipid profiles and proinflammatory cytokines in healthy and bronchopneumonic water buffalo calves. Therefore, sixty water buffalo calves (9±1 month old, 175±15 kg) were divided into two equal groups, the first group represented healthy, control, calves whereas calves of the second group were affected with bronchopneumonia. Total leukocytic and differential counts were determined. Serum total pr...

  10. Integrated Review of the Association of Cytokines with Fibromyalgia and Fibromyalgia Core Symptoms

    OpenAIRE

    Menzies, Victoria; Lyon, Debra

    2009-01-01

    Fibromyalgia (FMS) is a chronic widespread pain and fatigue syndrome that affects 3 to 6 million adults in the United States. Core symptoms of fibromyalgia include pain, fatigue, and mood and sleep disturbances. To date, consensus has not been reached among researchers regarding the pathogenesis of FMS nor the specific role of cytokine activation on the neuroendocrine-immune response patterns in persons with FMS. The purpose of this article is to describe and synthesize the results of researc...

  11. Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

    Directory of Open Access Journals (Sweden)

    Morawetz R.A.

    1998-01-01

    Full Text Available The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

  12. Sensitization associated with stressors and cytokine treatments.

    Science.gov (United States)

    Anisman, Hymie; Merali, Zul; Hayley, Shawn

    2003-04-01

    Like stressors, interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) increase hypothalamic-pituitary-adrenal (HPA) activity and monoamine turnover at hypothalamic and extrahypothalamic sites. These effects can be re-elicited more readily upon reintroduction of these challenges (sensitization), depending on their time of re-exposure and the particular system being assessed. Following TNF-alpha administration, the co-expression of corticotropin releasing hormone (CRH) and arginine vasopressin increased within the median eminence, peaking 7-14 days after treatment, and was associated with an early corticosterone sensitization. However, the re-elicitation of sickness symptoms and corticosterone release was most pronounced at lengthy re-exposure intervals (28 days), possibly reflecting histamine release from mast cells. In addition, the cytokine engendered the sensitization of norepinephrine and serotonin utilization, and CRH immunoreactivity at mesocorticolimbic sites, but these effects were most prominent at brief re-exposure intervals (1-7 days). Cytokines may independently prime multiple regulatory systems, and by virtue of the neurochemical changes imparted, have both immediate and proactive influences on the evolution of psychopathology. PMID:12676571

  13. Cytokine profile in elderly patients with sepsis

    Directory of Open Access Journals (Sweden)

    Kumar Anil

    2009-01-01

    Full Text Available Context: Sepsis is a serious health problem in the elderly with a high degree of mortality. There is very limited data available in elderly subjects regarding the markers for sepsis. Development of good markers will help in overall management and prediction of sepsis. Objectives: Serial estimation of Interleukin-6 (IL-6 and Tumor Necrosis Factor-Alpha (TNF-α and their correlation with mortality in sepsis in elderly patients and to determine the influence of gender on cytokine production and mortality in elderly patients with sepsis. Settings and Design: The prospective study was conducted at our tertiary care center from April 2007 to September 2008. Elderly Patients satisfying the Systemic Inflammatory Response Syndrome (SIRS criteria were included. Methods and Material: TNF-α and IL-6 were estimated in 30 elderly patients admitted to our intensive care unit with SIRS and sepsis. The estimations were done on day 1, 3 and 7 of admission. Statistical Analysis Used: Student and paired ′t′ tests, and ANOVA, which were further followed up by post-hoc ′t′ tests with Bonferroni correction using SPSS. Results: Reducing levels of IL-6 levels from day 1 to 7 was found in the survivor group. TNF-α level was significantly low on day 1 in the nonsurvivor female group. Conclusions: Serial estimation of cytokines in elderly patients with sepsis will help in prediction of mortality. Female gender was an independent predictor of increased morality in critically ill patients with sepsis.

  14. Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections

    Directory of Open Access Journals (Sweden)

    Rodrigo Nunes Rodrigues-da-Silva

    2014-04-01

    Full Text Available Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.

  15. Effects of ACL Reconstructive Surgery on Temporal Variations of Cytokine Levels in Synovial Fluid

    Science.gov (United States)

    Bigoni, Marco; Gandolla, Marta; Sacerdote, Paola; Piatti, Massimiliano; Castelnuovo, Alberto; Franchi, Silvia; Gorla, Massimo; Munegato, Daniele; Gaddi, Diego; Pedrocchi, Alessandra; Omeljaniuk, Robert J.; Locatelli, Vittorio; Torsello, Antonio

    2016-01-01

    Anterior cruciate ligament (ACL) reconstruction restores knee stability but does not reduce the incidence of posttraumatic osteoarthritis induced by inflammatory cytokines. The aim of this research was to longitudinally measure IL-1β, IL-6, IL-8, IL-10, and TNF-α levels in patients subjected to ACL reconstruction using bone-patellar tendon-bone graft. Synovial fluid was collected within 24–72 hours of ACL rupture (acute), 1 month after injury immediately prior to surgery (presurgery), and 1 month thereafter (postsurgery). For comparison, a “control” group consisted of individuals presenting chronic ACL tears. Our results indicate that levels of IL-6, IL-8, and IL-10 vary significantly over time in reconstruction patients. In the acute phase, the levels of these cytokines in reconstruction patients were significantly greater than those in controls. In the presurgery phase, cytokine levels in reconstruction patients were reduced and comparable with those in controls. Finally, cytokine levels increased again with respect to control group in the postsurgery phase. The levels of IL-1β and TNF-α showed no temporal variation. Our data show that the history of an ACL injury, including trauma and reconstruction, has a significant impact on levels of IL-6, IL-8, and IL-10 in synovial fluid but does not affect levels of TNF-α and IL-1β. PMID:27313403

  16. Th1/Th2 cytokines and their genotypes as predictors ofhepatitis B virus related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant typeof primary liver cancer, is one of the most serious lifethreateningmalignancies, worldwide. In majority ofthe cases, HCC develops after prolonged and persistentchronic liver disease. hepatitis B virus (HBV) or HCVinfection is prominent etiological factors, attributing to this condition. It has been well documented that HBV,being the inducer of chronic inflammation, is the maincausative agent in causing HCC, particularly in Asiancountries. The HBV infection leads to a wide range ofclinical symptoms from carrier state to malignancy.Cytokines being immune-modulatory molecules, arethe key mediators in the defense mechanism againstviral infection. In this regard, this review will detail thesubstantial role of key Th1: interleukin 1 (IL-1), IL-2,IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4,IL-10 and non Th1/Th2: IL-6, transforming growthfactor-β1 cytokines genotypes in analyzing the variabilityin the clinical manifestations in an HBV-afflicted individual,which might finally, culminates into HCC. Since cytokineproduction is regulated genetically, the cytokine promoterregion single-nucleotide polymorphisms induced changes,greatly affects the cytokine production, thus resulting intodifferential outcome of immune balance.

  17. Changes in proinflammatory cytokines and white matter in chronically stressed rats

    Directory of Open Access Journals (Sweden)

    Yang P

    2015-03-01

    Full Text Available Ping Yang,1 Zhenyong Gao,1 Handi Zhang,1 Zeman Fang,1 Cairu Wu,1 Haiyun Xu,1,2 Qing-Jun Huang1 1Mental Health Center, 2Department of Anatomy, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Although the pathogenesis of depression, an incapacitating psychiatric ailment, remains largely unknown, previous human and animal studies have suggested that both proinflammatory cytokines and altered oligodendrocytes play important roles in the condition. This study examined these two factors in the brains of rats following unpredictable chronic mild stress for 4 weeks, with the hypothesis that chronic stress may affect oligodendrocytes and elevate proinflammatory cytokines in the brain. After suffering unpredictable stressors for 4 weeks, the rats showed depression-like behaviors, including decreased locomotion in the open field, increased immobility time in the forced swim test, and decreased sucrose consumption and less sucrose preference when compared with controls. Immunohistochemical staining of brain sections showed higher immunoreactivity of proinflammatory cytokines in certain brain regions of stressed rats compared with controls; lower immunoreactivity of myelin basic protein and fewer mature oligodendrocytes were seen in the prefrontal cortex, but no demyelination was detected. These results are interpreted and discussed in the context of recent findings from human and animal studies. Keywords: cytokines, depression, myelination, oligodendrocytes, stress 

  18. Stress and cytokine-elicited neuroendocrine and neurotransmitter sensitization: implications for depressive illness.

    Science.gov (United States)

    Hayley, Shawn; Merali, Zul; Anisman, Hymie

    2003-03-01

    Stressful events, by their effects on neurotransmitter and neuroendocrine processes, are thought to favor the development or exacerbation of depressive illness. In as much as immunological challenge, may provoke stressor-like neuroendocrine and central neurochemical changes, the view was offered that immune activation essentially acts like a stressor and may contribute to the evolution of affective illness. In this respect, viral and bacterial infections appear to influence behavioral/metabolic (e.g. fever, anorexia, somnolence) and neurotransmitter functioning through the release of cytokines, which act as messengers between the immune system and brain. The present report provides a brief overview of the neurochemical consequences of proinflammatory cytokine treatments, particularly the actions of interleukin (IL)-1beta and tumor necrosis factor-alpha. As well, synergy with psychogenic and neurogenic stressors are described, as are data showing that cytokines, like stressors, may have time-dependent proactive (sensitization) effects, so that reexposure to the treatments greatly augments hypothalamic-pituitary-adrenal activity, as well as central neurochemical changes. Indeed, the neurotransmitter alterations are not restricted to hypothalamic nuclei, but occur in several extrahypothalamic sites, including various limbic regions. It is suggested that by virtue of these neurochemical changes, cytokines may have both immediate and proactive effects on mood states. PMID:12637204

  19. Leptin enhances the release of cytokines by peripheral blood mononuclear cells from acute multiple sclerosis patients

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To explore the effect of leptin on cytokine production by PBMCs obtained from MS patients either in acute (relapse) or in stable (nonrelapse) phase of disease. Methods PBMCs were collected from 25 untreated acute MS patients, 11 stable MS patients and 20 healthy controls. PBMCs were cultured either with RPMI-1640 alone or with leptin (1.25 nmol/ml), phytohemagglutinin (PHA) ( 100 μg/ml), and leptin + PHA. 72 h later the supernate of the culture medium were collected and stored at -70℃. The pro-inflammatory cytokine (IFN-γ) concentration were determined using an enzyme-linked immunosorbent assay ( ELISA), and the anti-inflammatory cytokine (IL-4) concentration were investigated by radioimmunity methods. Results Our data showed that leptin induced IFN-γproduction by PBMCs of patients in an acute phase of disease but not in a stable phase or in healthy controls. Moreover, we found that PHA induced IL-4 production by PBMCs of patients in an acute phase of disease, but leptin inhibited this ability of PHA. Conclusion Leptin can affect on pro- and anti-inflammatory cytokine production by PBMCs collected from MS patients, may be this connected with leptin increase the susceptiveness of MS.

  20. Three-Dimensional Gradients of Cytokine Signaling between T Cells.

    Directory of Open Access Journals (Sweden)

    Kevin Thurley

    2015-04-01

    Full Text Available Immune responses are regulated by diffusible mediators, the cytokines, which act at sub-nanomolar concentrations. The spatial range of cytokine communication is a crucial, yet poorly understood, functional property. Both containment of cytokine action in narrow junctions between immune cells (immunological synapses and global signaling throughout entire lymph nodes have been proposed, but the conditions under which they might occur are not clear. Here we analyze spatially three-dimensional reaction-diffusion models for the dynamics of cytokine signaling at two successive scales: in immunological synapses and in dense multicellular environments. For realistic parameter values, we observe local spatial gradients, with the cytokine concentration around secreting cells decaying sharply across only a few cell diameters. Focusing on the well-characterized T-cell cytokine interleukin-2, we show how cytokine secretion and competitive uptake determine this signaling range. Uptake is shaped locally by the geometry of the immunological synapse. However, even for narrow synapses, which favor intrasynaptic cytokine consumption, escape fluxes into the extrasynaptic space are expected to be substantial (≥20% of secretion. Hence paracrine signaling will generally extend beyond the synapse but can be limited to cellular microenvironments through uptake by target cells or strong competitors, such as regulatory T cells. By contrast, long-range cytokine signaling requires a high density of cytokine producers or weak consumption (e.g., by sparsely distributed target cells. Thus in a physiological setting, cytokine gradients between cells, and not bulk-phase concentrations, are crucial for cell-to-cell communication, emphasizing the need for spatially resolved data on cytokine signaling.

  1. The human kidney as a regulator of body cytokine homeostasis

    OpenAIRE

    Bonanni, A.; A. Sofia; S. Saffioti; I. Mannucci; D. Verzola; P. Gramegna; L. Cappuccino; Garibotto, G.

    2011-01-01

    Evidence is accumulating that the human kidney is a major site for the removal of several cytokines and growth factors, which can accumulate in body pools in patients with acute and chronic kidney disease (CKD). In addition, progressive renal failure and the increase in circulating proinflammatory cytokines are associated with mortality, suggesting that altered cytokines handling by the kidney is associated with worse outcome. Also, the kidney itself may be damaged by signals arising by endot...

  2. The Association of Cytokines with Severe Dengue in Children

    OpenAIRE

    Mangione, Julia N.A.; Huy, Nguyen Tien; Lan, Nguyen Thi Phuong; Mbanefo, Evaristus Chibunna; Ha, Tran Thi Ngoc; Bao, Lam Quoc; Nga, Cao Thi Phi; Tuong, Vo Van; Dat, Tran Van; Thuy, Tran Thi; Tuan, Ha Manh; Huong, Vu Thi Que; Hirayama, Kenji

    2014-01-01

    Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case control ...

  3. The Association of Cytokines with Severe Dengue in Children

    OpenAIRE

    Mangione, Julia N.A.; Huy, Nguyen Tien; Lan, Nguyen Thi Phuong; Mbanefo, Evaristus Chibunna; Ha, Tran Thi Ngoc; Bao, Lam Quoc; Nga, Cao Thi Phi; Tuong, Vo Van; Dat, Tran Van; Thuy, Tran Thi; Tuan, Ha Manh; Huong, Vu Thi Que; Hirayama, Kenji

    2014-01-01

    Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case cont...

  4. Proinflammatory Cytokines in the Prefrontal Cortex of Teenage Suicide Victims

    OpenAIRE

    Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Ren, Xinguo; Fareed, Jawed; Hoppensteadt, Debra A.; Roberts, Rosalinda C.; ROBERT R CONLEY; Dwivedi, Yogesh

    2011-01-01

    Teenage suicide is a major public health concern, but its neurobiology is not well understood. Proinflammatory cytokines play an important role in stress and in the pathophysiology of depression—two major risk factors for suicide. Cytokines are increased in the serum of patients with depression and suicidal behavior; however, it is not clear if similar abnormality in cytokines occurs in brains of suicide victims. We therefore measured the gene and protein expression levels of proinflammatory ...

  5. Role of inflammatory cytokines in peripheral nerve injury☆

    OpenAIRE

    Fregnan, Federica; Muratori, Luisa; Simões, Anabel Rodriguez; Giacobini-Robecchi, Maria Giuseppina; Raimondo, Stefania

    2012-01-01

    Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflamma...

  6. The diverse applications of plasma

    Science.gov (United States)

    Sharma, Mukul; Dubey, Shivani; Darwhekar, Gajanan; Jain, Sudhir Kumar

    2015-07-01

    Plasma being the fourth state of matter has always been an attraction for Physicists and Chemists. With the advent of time, plasma energy has been recognized in having widening horizons in the field of Biomedical Sciences. Plasma medicine can be subdivided into three main fields; Non-thermal atmospheric-pressure direct plasma for medical therapy; Plasma-assisted modification of bio-relevant surfaces and Plasma-based bio-decontamination and sterilization. The basis of the research is that as it has free carrier molecules, it has the ability to target specific cells and regulate functions like wound healing. Plasma does not harm healthy human cells but can kill bacteria and possibly even cancer cells to help treat various diseases. Nosocomial infection control, prevention and containment of contagious diseases, disinfection of medical devices, surface treatment (heat and UV sensitive surfaces) are research of interest. Recent success in generating plasma at very low temperature ie. Cold plasma makes the therapy painless. It has the ability to activate cellular responses and important mechanisms in the body. They target specific molecules such as prothrombin for blood coagulation, cytokines for killing bacteria, and angiogenesis for tissue regeneration. Plasma has bactericidal, fungicidal and virucidal properties. Plasma technology has flourishing future in diverse fields like Textiles, Nanofabrication, Automotives, Waste management, Microbiology, Food Hygiene, Medical Science like Skin treatments, sterilisation of wounds, Hand disinfection, Dental treatments etc. Food hygiene using plasma can be achieved in disinfection of food containers, food surface disinfection, hygiene in food handling, preparation and packaging. Therefore Plasma is most promising field for budding Scientist for fluorishing research in Biological Sciences.

  7. The diverse applications of plasma

    International Nuclear Information System (INIS)

    Plasma being the fourth state of matter has always been an attraction for Physicists and Chemists. With the advent of time, plasma energy has been recognized in having widening horizons in the field of Biomedical Sciences. Plasma medicine can be subdivided into three main fields; Non-thermal atmospheric-pressure direct plasma for medical therapy; Plasma-assisted modification of bio-relevant surfaces and Plasma-based bio-decontamination and sterilization. The basis of the research is that as it has free carrier molecules, it has the ability to target specific cells and regulate functions like wound healing. Plasma does not harm healthy human cells but can kill bacteria and possibly even cancer cells to help treat various diseases. Nosocomial infection control, prevention and containment of contagious diseases, disinfection of medical devices, surface treatment (heat and UV sensitive surfaces) are research of interest. Recent success in generating plasma at very low temperature ie. Cold plasma makes the therapy painless. It has the ability to activate cellular responses and important mechanisms in the body. They target specific molecules such as prothrombin for blood coagulation, cytokines for killing bacteria, and angiogenesis for tissue regeneration. Plasma has bactericidal, fungicidal and virucidal properties. Plasma technology has flourishing future in diverse fields like Textiles, Nanofabrication, Automotives, Waste management, Microbiology, Food Hygiene, Medical Science like Skin treatments, sterilisation of wounds, Hand disinfection, Dental treatments etc. Food hygiene using plasma can be achieved in disinfection of food containers, food surface disinfection, hygiene in food handling, preparation and packaging. Therefore Plasma is most promising field for budding Scientist for fluorishing research in Biological Sciences

  8. The diverse applications of plasma

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Mukul, E-mail: mukulsharma@acropolis.edu.in; Darwhekar, Gajanan, E-mail: gdarwhekar@acropolis.edu.in [Acropolis Institute of Pharmaceutical Education & Research, Indore MP India (India); Dubey, Shivani, E-mail: dubeyshivani08@rediffmail.com [Mata Gujri College of Professional Studies, Indore MP India (India); Jain, Sudhir Kumar, E-mail: sudhirkjain1@rediffmail.com [School of Studies in Microbiology, Vikram University, Ujjain MP India (India)

    2015-07-31

    Plasma being the fourth state of matter has always been an attraction for Physicists and Chemists. With the advent of time, plasma energy has been recognized in having widening horizons in the field of Biomedical Sciences. Plasma medicine can be subdivided into three main fields; Non-thermal atmospheric-pressure direct plasma for medical therapy; Plasma-assisted modification of bio-relevant surfaces and Plasma-based bio-decontamination and sterilization. The basis of the research is that as it has free carrier molecules, it has the ability to target specific cells and regulate functions like wound healing. Plasma does not harm healthy human cells but can kill bacteria and possibly even cancer cells to help treat various diseases. Nosocomial infection control, prevention and containment of contagious diseases, disinfection of medical devices, surface treatment (heat and UV sensitive surfaces) are research of interest. Recent success in generating plasma at very low temperature ie. Cold plasma makes the therapy painless. It has the ability to activate cellular responses and important mechanisms in the body. They target specific molecules such as prothrombin for blood coagulation, cytokines for killing bacteria, and angiogenesis for tissue regeneration. Plasma has bactericidal, fungicidal and virucidal properties. Plasma technology has flourishing future in diverse fields like Textiles, Nanofabrication, Automotives, Waste management, Microbiology, Food Hygiene, Medical Science like Skin treatments, sterilisation of wounds, Hand disinfection, Dental treatments etc. Food hygiene using plasma can be achieved in disinfection of food containers, food surface disinfection, hygiene in food handling, preparation and packaging. Therefore Plasma is most promising field for budding Scientist for fluorishing research in Biological Sciences.

  9. Systemic Cytokine and Interferon Responsiveness Patterns in HIV and HCV Mono and Co-Infections

    OpenAIRE

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael; Bordon, Jose

    2014-01-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV+/HCV+), HCV mono-infected (HIV−/HCV+), HIV mono-infected (HIV+/HCV−) female patients and HIV- and HCV-uninfected women (HIV−/HCV−) who had en...

  10. Urinary cytokines in Schistosoma haematobium-infected schoolchildren from Tana Delta District of Kenya

    DEFF Research Database (Denmark)

    Njaanake, Kariuki H.; Simonsen, Paul Erik; Vennervald, Birgitte J;

    2014-01-01

    , for the first time, reports on the relationship between selected cytokines in urine and infection with S. haematobium in children from an area highly affected by this parasite. METHODS: Children aged 5-12 years from two primary schools in Tana Delta District of Kenya were examined for S. haematobium...

  11. Patterns of Local and Systemic Cytokines in Bacterial Meningitis and its Relation with Severity and Long-Term Sequelae

    OpenAIRE

    Federico Perdomo-Celis; Miguel A. Torres; Henry Ostos; Javier Gutierrez-Achury; Víctor Molano; Luis F. Durán; Guillermo González; Narváez, Carlos F.

    2015-01-01

    Bacterial meningitis (BM) is a pyogenic infection present in the subarachnoid space, potentially fatal and frequently associated with neurological sequelae. During BM, cytokines (CTs) are locally produced. We sought to determine the CTs’ clinical role as disease severity predictors in adults, which is not completely clear. Using a bead-based flow cytometric assay, levels of six CTs were determined in cerebrospinal fluid (CSF) and plasma from 18 adult BM patients and 19 uninfected controls. Lo...

  12. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK

    OpenAIRE

    Vuslat Yilmaz; Piraye Oflazer; Fikret Aysal; Hacer Durmus; Kostas Poulas; Yentur, Sibel P.; Yesim Gulsen-Parman; Socrates Tzartos; Alexander Marx; Erdem Tuzun; Feza Deymeer; Güher Saruhan-Direskeneli

    2015-01-01

    Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in pat...

  13. Corticosteroid Therapy, Vitamin D Status, and Inflammatory Cytokine Profile in the HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome

    OpenAIRE

    Conesa-Botella, Anali; Meintjes, Graeme; Coussens, Anna K.; van der Plas, Helen; Goliath, Rene; Schutz, Charlotte; Moreno-Reyes, Rodrigo; Mehta, Meera; Martineau, Adrian R.; Wilkinson, Robert J.; Colebunders, Robert; Wilkinson, Katalin A.

    2012-01-01

    Background . Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis starting antiretroviral therapy (ART) is associated with hypercytokinemia. As adjunctive corticosteroid therapy and vitamin D have immunomodulatory properties, we investigated the relationship between cytokine/chemokine profiles, corticosteroid use, and vitamin D deficiency in TB-IRIS patients. Methods . Plasma from 39 TB-IRIS and 42 n...

  14. Aspects on the cytokine load in trauma with special reference to blood components and local versus systemic cytokine activity

    OpenAIRE

    Kristiansson, Marianne

    1997-01-01

    ASPECTS ON THE CYTOKINE LOAD IN TRAUMA with special reference to BLOOD COMPONENTS and LOCAL VERSUS SYSTEMIC CYTOKINE ACTIVITY by Marianne Kristiansson, M.D. Dissertation from the Department of Anaesthesiology and Intensive Care, Huddinge University Hospital Karolinska Institute, Stockholm and Department of Clinical Immunology, Umeå University Hospital, Umeå, Sweden Cytokines and their inhibitors are thought to be involved in many of the pathophysiologi...

  15. Polymorphisms within the IL-1 gene cluster: effects on cytokine profiles in peripheral blood and whole blood cell cultures of patients with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis

    DEFF Research Database (Denmark)

    Poulsen, Anne Havemose; Sørensen, Lars Korsbaek; Bendtzen, Klaus; Holmstrup, Palle

    2007-01-01

    Genetic polymorphisms of cytokines have been associated with the susceptibility, severity, and clinical outcome of inflammatory diseases, such as periodontitis and chronic arthritis. An important question to address is how interleukin (IL)-1 polymorphisms affect the cytokine profiles of patients...... with such diseases....

  16. [Gene therapy with cytokines against cervical cancer].

    Science.gov (United States)

    Bermúdez-Morales, Victor Hugo; Peralta-Zaragoza, Oscar; Madrid-Marina, Vicente

    2005-01-01

    Gene therapy is an excellent alternative for treatment of many diseases. Capacity to manipulate the DNA has allowed direct the gene therapy to correct the function of an altered gene, to increase the expression of a gene and to favour the activation of the immune response. This way, it can intend the use of the DNA like medication able to control, to correct or to cure many diseases. Gene therapy against cancer has an enormous potential, and actually the use of the DNA has increased to control diverse cancer in animal models, with very encouraging results that have allowed its applications in experimental protocols in human. This work concentrates a review of the foundations of the gene therapy and its application on cervical cancer, from the point of view of the alterations of the immune system focused on the tumour micro-environment, and the use of the cytokines as immunomodulators. PMID:16983992

  17. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

    Science.gov (United States)

    Yilmaz, Vuslat; Oflazer, Piraye; Aysal, Fikret; Durmus, Hacer; Poulas, Kostas; Yentur, Sibel P; Gulsen-Parman, Yesim; Tzartos, Socrates; Marx, Alexander; Tuzun, Erdem; Deymeer, Feza; Saruhan-Direskeneli, Güher

    2015-01-01

    Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients

  18. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

    Directory of Open Access Journals (Sweden)

    Vuslat Yilmaz

    Full Text Available Neuromuscular transmission failure in myasthenia gravis (MG is most commonly elicited by autoantibodies (ab to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON. Peripheral blood mononuclear cells (PBMC were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and Mu

  19. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis.

    Science.gov (United States)

    Kjølhede, T; Dalgas, U; Gade, A B; Bjerre, M; Stenager, E; Petersen, T; Vissing, K

    2016-07-01

    Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying attention to the medical treatments of the patient. At present, PwMS are routinely enrolled in immunosuppressive medication, but exercise-induced immunomodulatory effects have not been investigated under these circumstances. The objective of this study was to investigate the acute and chronic cytokines responses to resistance exercise training in medicated PwMS. Thirty-five people with relapsing-remitting multiple sclerosis (MS) treated with interferon (IFN)-β, were randomized to a 24-week progressive resistance training (PRT) or control group. Plasma interleukin (IL)-1β, IL-4, IL-10, IL-17F, IL-23, tumor necrosis factor-α and IFN-γ were measured before and after 24 weeks of PRT. The acute effect was evaluated following standardized single-bout resistance exercise in the untrained and the trained state. No changes were observed in resting cytokine levels after PRT. However, an indication of reduced IL-17F secretion following resistance exercise was observed in the trained compared with the untrained state. This study suggests little acute and chronic effect of PRT on cytokine levels in IFN-treated PwMS. PMID:26105554

  20. Increased miR-155 expression in peripheral blood mononuclear cells of primary immune thrombocytopenia patients was correlated with serum cytokine profiles.

    Science.gov (United States)

    Qian, Bao-Hua; Ye, Xin; Zhang, Lei; Sun, Yi; Zhang, Jian-Rong; Gu, Ming-Li; Qin, Qin; Chen, Jie; Deng, An-Mei

    2015-01-01

    We investigated the possible pathogenic role of a microRNA (miR-155) in primary immune thrombocytopenia (ITP). We used quantitative real-time PCR to determine the relative expression of miR-155 and SOCS1 (suppressor of cytokine signaling) mRNA in peripheral blood mononuclear cells (PBMCs) from 28 ITP patients and 28 healthy controls. Cytokine plasma levels were determined by ELISA. Possible associations between miR-155 levels and serum cytokine concentrations were assessed using Spearman or Pearson correlation analysis. Seven naive ITP patients were followed and the effects of medical treatment on miR-155 levels were assessed. Compared to healthy controls, ITP patients had increased miR-155 and decreased SOCS1 mRNA levels. ITP patients also had increased plasma IL-17A and decreased IL-4, IL-10 and TGF-β1 levels. miR-155 levels were negatively correlated with platelet counts, SOCS1 mRNA levels, and the plasma levels of IL-4, IL-10 and TGF-β1, but positively correlated with plasma IL-17A levels. Medical treatment for ITP decreased miR-155 levels. Thus, our results suggest that miR-155 might be involved in the pathogenesis of ITP by regulating cytokine profiles, which may be mediated by miR-155 targeting SOCS1. PMID:25413124

  1. The changes of inflammatory cytokines and their clinical significance in patients of inferior ST-segment elevation acute myocardial infarction with anterior ST-segment depression

    Institute of Scientific and Technical Information of China (English)

    叶明

    2014-01-01

    Objective To investigate the level of Hs-CRP,Fib,IL-6,TNF-α,MDA,SOD,and analyze the correlation between the level of plasma inflammatory cytokines and clinical significance in patients with anterior ST-segment depression.Methods We chose 360 patients with inferior ST Segment elavation acute myocardial infarction from May 2007 to Sep 2012 in emergency department of

  2. Novel cytokines and cytokine-producing T cells in allergic disorders.

    Science.gov (United States)

    Wisniewski, Julia A; Borish, Larry

    2011-01-01

    Allergic diseases reflect various pathways of T lymphocyte inflammation and largely comprise T helper (Th) 2-associated processes. Recent investigations have identified pathways involved in promoting Th2 responses. Additionally, novel T-cell subtypes, each with its own distinct cytokine profile, contribute to the heterogeneous presentations of allergic diseases. This article focuses on recent developments including novel effector (nuocytes, Th9, and Th22) and regulatory T-cell (Treg) families of lymphocytes as well as cytokines that are central in driving Th2 differentiation (interleukin [IL]-4, IL-9, IL-25, thymic stromal lymphopoietin [TSLP], and IL-33). Recent literature and investigations were reviewed. Unregulated IL-25, TSLP, and IL-33 activity results in activation of Th2 cells, mast cells, dendritic cells, eosinophils, and basophils, leading to inflammatory processes that define allergic disease. As such, these cytokines are central mediators capable of instigating the inflammatory processes responsible for allergen-mediated diseases. The previous paradigm of Th1/Th2 imbalance driving allergic disease is expanded by identification of novel T helper families (nuocytes, Th9, Th17, and Th22) with their signature cytokines, which provide alterative avenues for investigation of neutrophil-predominant asthma and other heterogeneous presentations of allergic diseases. IL-25, TSLP, and IL-33 are attractive targets for therapeutics designed to ameliorate Th2-mediated diseases such as allergic rhinitis and asthma. Moreover, the ability to delineate novel regulatory and effector T-cell lineages among CD4(+) T cells challenges the Th1/Th2 paradigm of allergic disease and invites further avenues of investigation into the role of these cells in allergic disease. PMID:21439160

  3. Cytokine polymorphisms in sickle cell disease and the relationship with cytokine expression.

    Science.gov (United States)

    Olenscki Gilli, Simone Cristina; Pericole, Fernando Vieira; Benites, Bruno Deltreggia; Sippert, Emilia Ângela; Castilho, Lilian Maria; Addas-Carvalho, Marcelo; Olalla Saad, Sara Teresinha

    2016-07-01

    Sickle cell disease is a chronic inflammatory condition characterized by elevated levels of inflammatory cytokines, which may be regulated by genetic polymorphisms and could be associated with diverse disease presentations and alloimmunization. The aim of this study was to evaluate Treg and Th17 cell frequencies, cytokine gene polymorphisms, and their association with cytokine expression profile in patients with sickle cell disease. For that purpose, we evaluated the IL intron 3 variable number tandem repeat (VNTR, genotypes 1.1, 1.2, 2.2, and 2.3), IL4-T590C>T, IL6-174G>C, TNFα-308G>A, IL10-819T>C, IL10-592A>C, and IL10-1082A>G polymorphisms and their correlation with TGFβ, IL4, IL6, and IL10 gene expression in sickle cell patients. We observed a significant decrease in Treg frequency together with a substantial increase in Th17 response in patients with sickle cell disease compared with healthy controls (p sickle cell disease than in Afro-Brazilian descendent controls (p sickle cell patients when compared with controls (p = 0.01, 0.03, and sickle cell patients and must be further investigated in larger cohorts to better characterize individual variations in immune responses and new markers for disease morbidity. PMID:27026283

  4. Role of inflammatory cytokines in peripheral nerve injury

    Institute of Scientific and Technical Information of China (English)

    Federica Fregnan; Luisa Muratori; Anabel Rodriguez Sim(o)es; Maria Giuseppina Giacobini-Robecchi; Stefania Raimondo

    2012-01-01

    Inflammatory events occurring in the distal part of an injured peripheral nerve have,nowadays,a great resonance.Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery.The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration.Cytokines can be divided into pro-and anti-inflammatory cytokines that upregutate and downregulate,respectively,the production of inflammatory mediators.While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages,anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines,thus determining the end of the process.In this review,we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration.In particular,we focus on interleukin-1,interleukin-2,interleukin-6,tumor necrosis factor-β,interleukin-10 and transforming growth factor-β.

  5. Cytokine gene polymorphisms associated with symptomatic parvovirus B19 infection

    OpenAIRE

    Kerr, J R; McCoy, M; Burke, B; Mattey, D L; Pravica, V.; Hutchinson, I V

    2003-01-01

    Background: The immune system has been implicated in the pathogenesis of certain clinical manifestations of parvovirus B19 infection, including rash and arthralgia. Cytokines feature in the pathogenesis of parvovirus B19 infection, so inherited variability in cytokine responses to B19 infection might have a bearing on the symptomatology of parvovirus B19 infection.

  6. Anti-cytokine vaccines and the immunotherapy of autoimmune diseases

    OpenAIRE

    Wraith, David C

    2006-01-01

    Three papers in this issue of the European Journal of Immunology describe the use of cytokine vaccines to prevent autoimmune disease in experimental animals. The vaccines are based on interleukin 17 (IL-17), a cytokine that has recently been shown to play a central role in inflammation.

  7. Cytokines: abnormalities in major depression and implications for pharmacological treatment.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.

  8. Anti-cytokine therapies in T1D

    DEFF Research Database (Denmark)

    Nepom, Gerald T; Ehlers, Mario; Mandrup-Poulsen, Thomas

    selective cytokine blockade as a component of preventative or interventional immunotherapy. The rationale and status of inhibitory therapy directed against IL-1, TNF, IL-12, IL-23, and IL-6 are discussed, towards a goal of using cytokine inhibition as a therapeutic platform to establish an in vivo milieu...

  9. Inflammatory cytokines and risk of coronary heart disease

    DEFF Research Database (Denmark)

    Kaptoge, Stephen; Seshasai, Sreenivasa Rao Kondapally; Gao, Pei;

    2014-01-01

    Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta...

  10. Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies

    Directory of Open Access Journals (Sweden)

    David Barrera

    2015-08-01

    Full Text Available Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

  11. Cytokines and adhesion molecules in multiple sclerosis patients treated with interferon-beta1b

    DEFF Research Database (Denmark)

    Jensen, Jakob; Krakauer, Martin; Sellebjerg, Finn

    2005-01-01

    Multiple sclerosis (MS), an inflammatory, demyelinating disease of the central nervous system (CNS), is thought to be caused by a T cell-mediated attack on CNS myelin and axons. Recombinant interferon (IFN)-beta is an established treatment of multiple sclerosis, and is known to reduce the number of...... disease relapses and the development of irreversible symptoms and signs of disease. The mechanism of action of IFN-beta treatment is, however, not completely understood. Previous studies have suggested major effects on mononuclear cell cytokine production and T cell migration, but results have been...... inconsistent. We found decreases in CD4 and CD8 T cell expression of the CD49d/VLA-4 molecule, increases in plasma concentrations of soluble vascular cell adhesion molecule (sVCAM-1), and increases in plasma concentrations of tumor necrosis factor and interleukin (IL)-12 p40 chain in patients with MS who were...

  12. Plasma Levels of Monocyte Chemotactic Protein 3 and Beta-Nerve Growth Factor Increase with Amnestic Mild Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    Kang Soo Lee; Ji Hyung Chung; Kyung Hye Lee; Min-Jeong Shin; Byoung Hoon Oh; Soo Hyung Lee; Chang Hyung Hong

    2009-01-01

    A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (β-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and β-NGF may be useful in differentiating subtypes of MCI. Cellular & Molecular Immunology.

  13. Non-association of IL-12 +1188 and IFN-γ +874 polymorphisms with cytokines serum level in occult HBV infected patients

    Directory of Open Access Journals (Sweden)

    Mohammad K Arababadi

    2011-01-01

    Full Text Available Background/Aim: Occult hepatitis B infection (OBI is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-γ and +1188 of IL-12 with their serum level in patients suffering from OBI. Materials and Methods: In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen (HBsAg and anti-HBc by ELISA. The HBsAg - /anti-HBc + samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-γ. In addition, the serum levels of IL-12 and IFN-γ were also determined by ELISA. Results: Results of this study demonstrated that, 352 (9.5% out of 3700 blood samples were HBsAg - /anti-HBc + and HBV-DNA was detected in 57/352 (16.1% of HBsAg - /anti-HBc + samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-γ were also not associated with serum level of cytokines. Conclusion: According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-γ would not affect the expression of both cytokines at serum level in OBI patients.

  14. Enhancement of survival and limitation of inflammatory response in total body irradiated mice treated with cytokines

    International Nuclear Information System (INIS)

    Full text: Inflammatory reaction is a classical feature of radiation exposure and radiation pneumonitis is a dose-limiting complication in the treatment of haematological disorders treated with total body irradiation. Vascular injury is often considered to be a primary determinant of tissue dysfunction and is likely responsible for the chronic and progressive nature of delayed radiation injury. In the present study, we evaluated the influence of anti-inflammatory cytokines (IL-4, IL-11) in association with thrombopoietin (TPO) on the 30-day mouse survival as well as on systemic and lung inflammatory response and on microvascular permeability. Mice were total body irradiated with the supra lethal dose of 10 Gy (137Cs). TPO alone allowed the survival of 45% of the mice although 90% of mice treated with IL-4/TPO or IL-11/TPO survived. TPO, alone or in association, significantly decreased the over-production of the chemokine KC observed in the plasma of irradiated mice 10 to 18 days following exposure, with a higher efficacy for TPO when associated with IL-4 or IL-11. No major effect of treatments was seen on the radiation-induced lung endothelial cell activation, as illustrated by the lack of efficacy of the treatment on PECAM-1 and P-Selectin over-expression with immunohistochemistry. However, both combined-cytokine treatment limited the radiation-induced vascular leakage for 70 kD-Dextran across the mesenteric venules measured in irradiated mice four days after exposure. The efficacy of treatment with cytokines on the 30-day survival of mice might result from limitation of endothelial cell damage. In addition cytokine treatment reduced the radiation-induced vascular hyperpermeability which could result in limitation of systemic inflammatory reaction

  15. Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity.

    Science.gov (United States)

    Meulenbroeks, Chantal; van der Lugt, Jaco J; van der Meide, Nathalie M A; Willemse, Ton; Rutten, Victor P M G; Zaiss, Dietmar M W

    2015-01-01

    The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH) is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus). We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected and healthy ponies and cytokine expression was determined by RT-PCR. In addition, allergen-specific antibody titers were measured and cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined. 24 hrs after allergen injection, a significant increase in mRNA expression of the type-2 cytokine IL-4 was observed in the skin of IBH-affected Shetland ponies. In the skin of healthy ponies, however, an increase in IFNγ mRNA expression was found. Analysis of allergen-specific antibody titers revealed that all animals produced allergen-specific antibodies, and allergen-specific stimulation of CD4 T-cells revealed a significant higher percentage of IFNγ-expressing CD4 T-cells in healthy ponies compared to IBH-affected ponies. These data indicate that horses not affected by IBH, in contrast to the so far established dogma, are not immunologically ignorant but have a Th1-skewed allergen-specific immune response that appears to protect against IBH-associated symptoms. To our knowledge this is the first demonstration of a natural situation, in which an allergen-specific immune skewing is protective in an allergic disorder. PMID:25901733

  16. Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hong-Bao [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Ma, Le [Department of Public Health, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Miao, Yu-Wang [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Lu, Yan [Department of Clinical Laboratory, Sanaitang Hospital, Lanzhou 730030 (China); Song, Xin-Ai [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-09-01

    The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91{sup phox}) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension.

  17. Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

    International Nuclear Information System (INIS)

    The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91phox) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension

  18. 384-Well Multiplexed Luminex Cytokine Assays for Lead Optimization.

    Science.gov (United States)

    Tang, Huaping; Panemangalore, Reshma; Yarde, Melissa; Zhang, Litao; Cvijic, Mary Ellen

    2016-07-01

    Cytokines serve as a major mechanism of communication between immune cells and are the functional molecules at the end of immune pathways. Abnormalities in cytokines are involved in a wide variety of diseases, including chronic inflammation, autoimmune diseases, and cancer. Cytokines are not only direct targets of therapeutics but also important biomarkers for assessing drug efficacy and safety. Traditionally, enzyme-linked immunosorbent assays (ELISA) were most popular for identifying and quantifying cytokines. However, ELISA is expensive, labor intensive, and low throughput. Here, we report the development of a miniaturized Luminex (Austin, TX) assay platform to establish a panel of high-throughput, multiplexed assays for measuring cytokines in human whole blood. The miniaturized 384-well Luminex assay uses animal studies and patient samples for translational research. PMID:27095819

  19. Role of IL-38 and Its Related Cytokines in Inflammation

    Directory of Open Access Journals (Sweden)

    Xianli Yuan

    2015-01-01

    Full Text Available Interleukin- (IL- 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.

  20. [Role of cytokines in the central nervous system].

    Science.gov (United States)

    Benavides, J; Toulmond, S

    1993-01-01

    Cytokines were first characterized as high-molecular weight modulators of the immune response. However they also play an important role in the CNS. Thus, some cytokines could influence the synaptic transmission or modulate the neuronal and glial growth during brain development or after brain injury. Activated glial cells appear to be the major cytokines producing cells. Some of these cytokines are glial cells mitogens, whilst others have a direct neurotrophic activity. These effects seem to be mediated by receptors similar to those of neurotrophic factors. Cytokines might be crucial factors in the evolution of different acute or chronic neuropathological processes such as ischemia, brain trauma, multiple sclerosis and Alzheimer's disease. Control of their effect on brain cells could allow prevention of brain damage observed in such pathologies. PMID:8091343

  1. Langerhans cell histiocytosis: a cytokine/chemokine-mediated disorder?

    Science.gov (United States)

    Garabedian, Lara; Struyf, Sofie; Opdenakker, Ghislain; Sozzani, Silvano; Van Damme, Jo; Laureys, Geneviève

    2011-09-01

    Langerhans cell histiocytosis (LCH) is a rare disorder characterized by an abnormal accumulation and/or proliferation of cells with a Langerhans cell phenotype. Although no clear cause of LCH has been identified, it has been postulated that LCH might be the consequence of an immune dysregulation, causing Langerhans cells to migrate to and accumulate at various sites. Production of cytokines and chemokines is a central feature of immune regulation. Cytokines are abundantly present within LCH lesions. We review here the potential role of cytokines and chemokines in the pathogenesis of LCH. The type, distribution, and number of different cytokines released within lesions can provide clues to the possible aetiology of LCH and, ultimately, might offer therapeutic possibilities using recombinant cytokines or antagonists for this disorder. PMID:22001902

  2. The TNF-family cytokine TL1A: from lymphocyte costimulator to disease co-conspirator.

    Science.gov (United States)

    Richard, Arianne C; Ferdinand, John R; Meylan, Françoise; Hayes, Erika T; Gabay, Odile; Siegel, Richard M

    2015-09-01

    Originally described in 2002 as a T cell-costimulatory cytokine, the tumor necrosis factor family member TNF-like factor 1A (TL1A), encoded by the TNFSF15 gene, has since been found to affect multiple cell lineages through its receptor, death receptor 3 (DR3, encoded by TNFRSF25) with distinct cell-type effects. Genetic deficiency or blockade of TL1A-DR3 has defined a number of disease states that depend on this cytokine-receptor pair, whereas excess TL1A leads to allergic gastrointestinal inflammation through stimulation of group 2 innate lymphoid cells. Noncoding variants in the TL1A locus are associated with susceptibility to inflammatory bowel disease and leprosy, predicting that the level of TL1A expression may influence host defense and the development of autoimmune and inflammatory diseases. PMID:26188076

  3. Pro- and anti-inflammatory cytokine gene single-nucleotide polymorphisms in inflammatory bowel disease.

    Science.gov (United States)

    López-Hernández, R; Valdés, M; Campillo, J A; Martínez-García, P; Salama, H; Bolarin, J M; Martínez, H; Moya-Quiles, M R; Minguela, A; Sánchez-Torres, A; Botella, C; Salgado, G; Miras, M; Carballo, F; Muro, M

    2015-02-01

    Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [Crohn's disease (CD) and ulcerative colitis (UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR-SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFβ [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1β [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFβ, IL10, IL6, IL1α, IL1β, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFβ, IL10, IL6 and IL1α, IL1β, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development. PMID:25359546

  4. Plasma properties

    International Nuclear Information System (INIS)

    This paper discusses the following topics: MHD plasma activity: equilibrium, stability and transport; statistical analysis; transport studies; edge physics studies; wave propagation analysis; basic plasma physics and fluid dynamics; space plasma; and numerical methods

  5. H pylori seropositivity and cytokine gene polymorphisms

    Institute of Scientific and Technical Information of China (English)

    Yasuaki Saijo; Eiji Yoshioka; Tomonori Fukui; Mariko Kawaharada; Fumihiro Sata; Hirokazu Sato; Reiko Kishi

    2007-01-01

    AIM: To investigate whether the pro- and antiinflammatory cytokine gene polymorphisms, IL1B-511C/T,IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C,TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5'nuclease assay.RESULTS: In gender- and age-adjusted logistic analyses,the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007).After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C;OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P =0.042: 1.04-6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14,P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C;OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However,the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine

  6. Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population.

    Directory of Open Access Journals (Sweden)

    Andrew K Turner

    2011-10-01

    Full Text Available Pathogens are believed to drive genetic diversity at host loci involved in immunity to infectious disease. To date, studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC; the role of genetic variation elsewhere in the genome as a basis for variation in pathogen resistance has rarely been explored in natural populations. Cytokines are signalling molecules with a role in many immunological and physiological processes. Here we use a natural population of field voles (Microtus agrestis to examine how genetic diversity at a suite of cytokine and other immune loci impacts the immune response phenotype and resistance to several endemic pathogen species. By using linear models to first control for a range of non-genetic factors, we demonstrate strong effects of genetic variation at cytokine loci both on host immunological parameters and on resistance to multiple pathogens. These effects were primarily localized to three cytokine genes (Interleukin 1 beta (Il1b, Il2, and Il12b, rather than to other cytokines tested, or to membrane-bound, non-cytokine immune loci. The observed genetic effects were as great as for other intrinsic factors such as sex and body weight. Our results demonstrate that genetic diversity at cytokine loci is a novel and important source of individual variation in immune function and pathogen resistance in natural populations. The products of these loci are therefore likely to affect interactions between pathogens and help determine survival and reproductive success in natural populations. Our study also highlights the utility of wild rodents as a model of ecological immunology, to better understand the causes and consequences of variation in immune function in natural populations including humans.

  7. Cytokine and Chemokine Signature in Elite Versus Viremic Controllers Infected with HIV.

    Science.gov (United States)

    Platten, Martin; Jung, Norma; Trapp, Susanna; Flossdorf, Pia; Meyer-Olson, Dirk; Schulze Zur Wiesch, Julian; Stephan, Christoph; Mauss, Stefan; Weiss, Verena; von Bergwelt-Baildon, Michael; Rockstroh, Jürgen; Fätkenheuer, Gerd; Lehmann, Clara

    2016-06-01

    HIV long-term nonprogressors (LTNPs) maintaining high CD4(+) T-cell counts without antiretroviral therapy (ART) are divided into elite controllers (ECs) with undetectable and viremic controllers (VCs) with low viral loads. Little is known about the long-term changes of T-cell subsets and inflammation patterns in ECs versus VCs. The aim of the study was to explore the long-term evolution of CD4(+) T-cell levels in LTNPs and to analyze cytokine profiles in ECs versus VCs. Nineteen ECs and 15 VCs were enrolled from the natural virus controller cohort (NaViC). T-cell counts were monitored over years, the mean annual change was calculated, and plasma concentrations of 25 cytokines were evaluated using a multiplex bead array. While absolute numbers of T cells did not differ between ECs and VCs over time, we observed a significant decrease of CD4(+) T-cell percentages in VCs, but not in ECs (median [interquartile range]: ECs: 37% [28-41] vs. VCs: 29% [25-34]; p = .02). ECs had lower levels of macrophage inflammatory protein-1β (MIP-1β, p = .003), interferon γ-induced protein-10 (IP-10, p = .03), and monokine induced by interferon-γ (MIG, p = .02). CD4(+) T-cell percentages inversely correlated with MIP 1-β (r = -0.42, p = .017) and IP-10 (r = -0.77, p < .0001). A subtle decline of CD4(+) T-cell percentages could be observed in VCs, but not in ECs, which was associated with higher plasma levels of proinflammatory cytokines. Hence, even low levels of HIV replication might go along with a progressive decline in CD4(+) T-cell counts in LTNPs. PMID:26751176

  8. Cytokine levels as biomarkers of radiation fibrosis in patients treated with breast radiotherapy

    International Nuclear Information System (INIS)

    Radiation fibrosis is not easily measurable although clinical scores have been developed for this purpose. Biomarkers present an alternative more objective approach to quantification, and estimation in blood provides accessible samples. We investigated if blood cytokines could be used to measure established fibrosis in patients who have undergone radiotherapy for breast cancer. We studied two cohorts treated by breast-conserving surgery and radiotherapy in the UK START Trial A, one with breast fibrosis (cases) and one with no or minimal fibrosis (controls). Two candidate cytokines, plasma connective tissue growth factor (CTGF) and serum interleukin-6 (IL6) were estimated by ELISA. Comparisons between cases and controls used the t-test or Mann–Whitney test and associations between blood concentration and clinical factors were assessed using the Spearman rank correlation coefficient. Seventy patients were included (26 cases, 44 controls). Mean time since radiotherapy was 9.9 years (range 8.3-12.0). No statistically significant differences between cases and controls in serum IL6 (median (IQR) 0.84 pg/ml (0.57-1.14), 0.75 pg/ml (0.41-1.43) respectively) or plasma CTGF (331.4 pg/ml (234.8-602.9), 334.5 pg/ml (270.0-452.8) were identified. There were no significant associations between blood cytokine concentration and age, fibrosis severity, breast size or time since radiotherapy. No significant difference in IL6 or CTGF concentrations was detected between patients with breast fibrosis and controls with minimal or no fibrosis

  9. Plasma accelerators

    International Nuclear Information System (INIS)

    Recently attention has focused on charged particle acceleration in a plasma by a fast, large amplitude, longitudinal electron plasma wave. The plasma beat wave and plasma wakefield accelerators are two efficient ways of producing ultra-high accelerating gradients. Starting with the plasma beat wave accelerator (PBWA) and laser wakefield accelerator (LWFA) schemes and the plasma wakefield accelerator (PWFA) steady progress has been made in theory, simulations and experiments. Computations are presented for the study of LWFA. (author)

  10. Involvement of three mechanisms in the alteration of cytokine responses by sodium methyldithiocarbamate

    International Nuclear Information System (INIS)

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the U.S. We recently reported that it alters the induction of cytokine production mediated though Toll-like receptor (TLR) 4 at relevant dosages in mice. Its chemical properties and evidence from the literature suggest thee potential mechanisms of action for this compound. It could either act as a free radical scavenger (by means of its free S-group) or promote oxidation by breaking down to form methylisothiocyanate, which can deplete glutathione. It is a potent copper chelator and may affect the availability of copper to a number of copper-dependent enzymes (including some signaling molecules). SMD induces a classical neuroendocrine stress response characterized by elevated serum corticosterone concentrations, which could affect cytokine production. Although each of these mechanisms could potentially contribute to altered cytokine responses, direct evidence is lacking. The present study was conducted to obtain such evidence. The role of redox balance was investigated by pretreating mice with N-acetyl cysteine (NAC), which increases cellular glutathione concentrations, before administration of SMD. NAC exacerbated the SMD-induced suppression of IL-12 and the SMD-induced enhancement of IL-10 in the serum. The role of copper chelation was investigated by comparing the effects of SMD with an equimolar dose to SMD that was administered in the form of a copper chelation complex. Addition of copper significantly decreased the action of SMD on IL-12 production but not on IL-10 production. The role of the stress response was investigated by pretreating mice with antagonists of corticosterone and catecholamines. This treatment partially prevented the action of SMD on IL-10 and IL-12 in the peritoneal fluid. The results suggest that all of the proposed mechanisms have some role in the alteration of cytokine production by SMD

  11. Plasma harmonics

    CERN Document Server

    Ganeev, Rashid A

    2014-01-01

    Preface; Why plasma harmonics? A very brief introduction Early stage of plasma harmonic studies - hopes and frustrations New developments in plasma harmonics studies: first successes Improvements of plasma harmonics; Theoretical basics of plasma harmonics; Basics of HHG Harmonic generation in fullerenes using few-cycle pulsesVarious approaches for description of observed peculiarities of resonant enhancement of a single harmonic in laser plasmaTwo-colour pump resonance-induced enhancement of odd and even harmonics from a tin plasmaCalculations of single harmonic generation from Mn plasma;Low-o

  12. Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines

    Directory of Open Access Journals (Sweden)

    Thurmond Robin L

    2010-06-01

    Full Text Available Abstract Background Airway remodeling and dysfunction are characteristic features of asthma thought to be caused by aberrant production of Th2 cytokines. Histamine H4 receptor (H4R perturbation has previously been shown to modify acute inflammation and Th2 cytokine production in a murine model of asthma. We examined the ability of H4R antagonists to therapeutically modify the effects of Th2 cytokine production such as goblet cell hyperplasia (GCH, and collagen deposition in a sub-chronic model of asthma. In addition, effects on Th2 mediated lung dysfunction were also determined. Methods Mice were sensitized to ovalbumin (OVA followed by repeated airway challenge with OVA. After inflammation was established mice were dosed with the H4R antagonist, JNJ 7777120, or anti-IL-13 antibody for comparison. Airway hyperreactivity (AHR was measured, lungs lavaged and tissues collected for analysis. Results Therapeutic H4R antagonism inhibited T cell infiltration in to the lung and decreased Th2 cytokines IL-13 and IL-5. IL-13 dependent remodeling parameters such as GCH and lung collagen were reduced. Intervention with H4R antagonist also improved measures of central and peripheral airway dysfunction. Conclusions These data demonstrate that therapeutic H4R antagonism can significantly ameliorate allergen induced, Th2 cytokine driven pathologies such as lung remodeling and airway dysfunction. The ability of H4R antagonists to affect these key manifestations of asthma suggests their potential as novel human therapeutics.

  13. Cognitive impairment effects of early life stress in adolescents can be predicted with early biomarkers: Impacts of sex, experience, and cytokines.

    Science.gov (United States)

    Grassi-Oliveira, Rodrigo; Honeycutt, Jennifer A; Holland, Freedom H; Ganguly, Prabarna; Brenhouse, Heather C

    2016-09-01

    Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2-21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population. PMID:27235636

  14. Revisiting the plasma sheath—dust in plasma sheath

    Science.gov (United States)

    Das, G. C.; Deka, R.; Bora, M. P.

    2016-04-01

    In this work, we have considered the formation of warm plasma sheath in the vicinity of a wall in a plasma with considerable presence of dust particles. As an example, we have used the parameters relevant in case of plasma sheath formed around surfaces of various solid bodies in space, though the results obtained in this work can be applied to any other physical situation such as laboratory plasma. In the ion-acoustic time scale, we neglect the dust dynamics. The dust particles affect the sheath dynamics by affecting the Poisson equation which determines the plasma potential in the sheath region. It is important to note that our calculations are valid only when the amount of dust particles is not sufficient so as to affect the plasma dynamics in the dust-acoustic time scale, but enough to affect the plasma sheath. We have assumed the current to a dust particle to be balanced throughout the analysis. This makes the grain potential dependent on plasma potential, which is then incorporated into the Poisson equation. The resultant numerical model becomes an initial value problem, which is described by a 1-D integro-differential equation, which is then solved self-consistently by incorporating the change in plasma potential caused by inclusion of the dust potential in the Poisson equation.

  15. Divergent T-Cell Cytokine Patterns in Inflammatory Arthritis

    Science.gov (United States)

    Simon, A. K.; Seipelt, E.; Sieper, J.

    1994-08-01

    A major immunoregulatory mechanism in inflammatory infections and allergic diseases is the control of the balance of cytokines secreted by Th1/Th2 subsets of T helper (Th) cells. This might also be true in autoimmune diseases; a Th2 pattern that prevents an effective immune response in infections with intracellular bacteria may favor immunosuppression in autoimmune diseases. The pattern of cytokine expression was compared in the synovial tissue from patients with a typical autoimmune disease, rheumatoid arthritis, and with a disorder with similar synovial pathology but driven by persisting exogenous antigen, reactive arthritis. We screened 12 rheumatoid and 9 reactive arthritis synovial tissues by PCR and in situ hybridization for their expression of T-cell cytokines. The cytokine pattern differs significantly between the two diseases; rheumatoid arthritis samples express a Th1-like pattern whereas in reactive arthritis interferon γ expression is accompanied by that of interleukin 4. Studying the expression of cytokines by in situ hybridization confirmed the results found by PCR; they also show an extremely low frequency of cytokine-transcribing cells. In a double-staining experiment, it was demonstrated that interleukin 4 is made by CD4 cells. These experiments favor the possibility of therapeutic intervention in inflammatory rheumatic diseases by means of inhibitory cytokines.

  16. Affect Regulation

    DEFF Research Database (Denmark)

    Pedersen, Signe Holm; Poulsen, Stig Bernt; Lunn, Susanne

    2014-01-01

    Gergely and colleagues’ state that their Social Biofeedback Theory of Parental Affect Mirroring” can be seen as a kind of operationalization of the classical psychoanalytic concepts of holding, containing and mirroring. This article examines to what extent the social biofeedback theory of parenta...

  17. Relationship between plasma analytes and SPARE-AD defined brain atrophy patterns in ADNI.

    Directory of Open Access Journals (Sweden)

    Jon B Toledo

    Full Text Available Different inflammatory and metabolic pathways have been associated with Alzheimeŕs disease (AD. However, only recently multi-analyte panels to study a large number of molecules in well characterized cohorts have been made available. These panels could help identify molecules that point to the affected pathways. We studied the relationship between a panel of plasma biomarkers (Human DiscoveryMAP and presence of AD-like brain atrophy patterns defined by a previously published index (SPARE-AD at baseline in subjects of the ADNI cohort. 818 subjects had MRI-derived SPARE-AD scores, of these subjects 69% had plasma biomarkers and 51% had CSF tau and Aβ measurements. Significant analyte-SPARE-AD and analytes correlations were studied in adjusted models. Plasma cortisol and chromogranin A showed a significant association that did not remain significant in the CSF signature adjusted model. Plasma macrophage inhibitory protein-1α and insulin-like growth factor binding protein 2 showed a significant association with brain atrophy in the adjusted model. Cortisol levels showed an inverse association with tests measuring processing speed. Our results indicate that stress and insulin responses and cytokines associated with recruitment of inflammatory cells in MCI-AD are associated with its characteristic AD-like brain atrophy pattern and correlate with clinical changes or CSF biomarkers.

  18. Studies on Stable Formulations for a Hydrophobic Cytokine

    OpenAIRE

    Hawe, Andrea

    2006-01-01

    The goal of the thesis was to analyze the impact of the formulation conditions on the stabilization of a hydrophobic cytokine. A standard way to formulate the cytokine at physiological pH is using Human Serum Albumin (HSA) as excipient. Based on a lyophilized formulation with mannitol as bulking agent and HSA as stabilizer analogous to commercially available systems, the impact of HSA-stabilizers, NaCl and pH on particle formation and stability of the cytokine in the liquid state was elucidat...

  19. Role of cytokine p40 family in multiple sclerosis

    OpenAIRE

    Brahmachari, S.; Pahan, K.

    2008-01-01

    Over the last couple of decades of neuro-immunological research, the p40 family of cytokines has emerged out as one of the most intriguing areas of interest because of multi-faceted roles of these cytokine in immune-modulation and inflammation. The IL-12, the most widely studied cytokine of this family, is well-characterized for its Th1-favoring activity, and therefore plays a key role in the pathophysiology of Th1-mediated autoimmune diseases like multiple sclerosis (MS). On the other hand, ...

  20. Cytokine-producing T cell subsets in human leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, Kåre

    2000-01-01

    Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokines...... leads to subclinical or mild infections. In mice, an infection leads to a polarisation of either Th1 or Th2 Leishmania antigen specific cells. In contrast, both Th1 and Th2 Leishmania antigen specific cells can be identified in humans cured from L. donovani infections. Theoretically, Th1 cells and Th2...

  1. Cytokine-Mediated Loss of Blood Dendritic Cells During Epstein-Barr Virus-Associated Acute Infectious Mononucleosis: Implication for Immune Dysregulation.

    Science.gov (United States)

    Panikkar, Archana; Smith, Corey; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A; Wykes, Michelle; Moss, Denis J; Rickinson, Alan; Balfour, Henry H; Khanna, Rajiv

    2015-12-15

    Acute infectious mononucleosis (IM) is associated with altered expression of inflammatory cytokines and disturbed T-cell homeostasis, however, the precise mechanism of this immune dysregulation remains unresolved. In the current study we demonstrated a significant loss of circulating myeloid and plasmacytoid dendritic cells (DCs) during acute IM, a loss correlated with the severity of clinical symptoms. In vitro exposure of blood DCs to acute IM plasma resulted in loss of plasmacytoid DCs, and further studies with individual cytokines showed that exposure to interleukin 10 could replicate this effect. Our data provide important mechanistic insight into dysregulated immune homeostasis during acute IM. PMID:26080368

  2. Expression of acute phase proteins and inflammatory cytokines in mouse mammary gland following Staphylococcus aureus challenge and in response to milk accumulation

    DEFF Research Database (Denmark)

    Nazemi, Sasan; Aalbæk, Bent; Kjelgaard-Hansen, Mads;

    2014-01-01

    We used a mouse model of pathogenic (Staphylococcus aureus) and non-pathogenic (teat sealing) mammary inflammation to investigate mRNA expression of several inflammatory cytokines and acute phase proteins (APP) in mammary tissue and liver, and the appearance of some of these factors in plasma and...... combination might provide a tool for diagnostic discrimination between mastitis caused by pathogenic invasion and milk accumulation, and hence allow for better targeting of antibiotic therapy. In comparison with mammary expression, expression of cytokines in liver tissue was up-regulated to a similar or...

  3. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines.

    Directory of Open Access Journals (Sweden)

    Xinyuan Li

    Full Text Available It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35 is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1 the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2 the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies.

  4. Study on the therapeutic effect of cytokine on acute radiation syndrome induced by 60Co γ ray exposure

    International Nuclear Information System (INIS)

    Objective: To examine the therapeutic effect of combined administration of rhIL-11 and rhG-CSF on acute radiation syndrome induced by 60Coγ ray exposure in beagles. Methods: Sixteen beagles were randomly divided into the control (n=5), symptomatic treatment group (n=5) and cytokine treatment group (n=6). All the beagles in the three groups were exposed to the whole-body irradiation of 60Co γ ray at a dose of 4.5 Gy. The animals in the second group accepted active symptomatic treatment. The animals in the cytokine treatment group were sub-cutaneously administered rhIL -11 and rhG -CSF besides active symptomatic treatment. Hemogram of peripheral blood, pristine apoptosis and necrosis ratio of nucleated cells, the content of IL-2 and IFN-γ in plasma and formation of bone marrow were used to evaluate the therapeutic effect. Results: In the cytokine treatment group, the animal' survival rate 45 days after exposure was increased and hemogram of peripheral blood was improved significantly. The rate of pristine apoptosis and necrosis of nucleated cell declined obviously. Early, the content of both IL-2 and IFN-γ in plasma was up significantly, then the content of IL-2 rapidly descended, but that of IFN-γ was relatively stable. Conclusion: The combined administration of rhIL-11 and rhG-CSF significantly improved the recovery of hematopoietic and immunological function. (authors)

  5. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

    Directory of Open Access Journals (Sweden)

    Kristi Alnek

    Full Text Available The production of several cytokines could be dysregulated in type 1 diabetes (T1D. In particular, the activation of T helper (Th type 1 (Th1 cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF and interleukin (IL-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α, Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8, but not human leukocyte antigen (HLA genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

  6. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes

    Science.gov (United States)

    Heilman, Kaire; Peet, Aleksandr; Varik, Karin; Uibo, Raivo

    2015-01-01

    The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease. PMID:26636339

  7. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    , experience and consumption are all strategic design tools applied by planners and architects. Whereas urban design in former modernist planning served merely functional or political means, urban design has increasingly become an aesthetical mediator of ideologies embedded in the urban field of life forces...... capitalism not only changes urban life and its means of production, it specifically influences the way the city is designed and how it unfolds as events (Anderson & Harrison 2010) and affective, emotional production (Pile 2009). Through examples of urban design and events in the Carlsberg City in Copenhagen...... and The High Line in Chelsea, New York, the paper sets out to define and question these affective modes of production. Whether these productions are socio-material practices consisting of ludic designs (Stevens 2007), temporary architecture or art installations or evental practices consisting of...

  8. Interactions between Cytokines, Congenital Anomalies of Kidney and Urinary Tract and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ana Cristina Simões e Silva

    2013-01-01

    Full Text Available Fetal hydronephrosis is the most common anomaly detected on antenatal ultrasound, affecting 1–5% of pregnancies. Postnatal investigation has the major aim in detecting infants with severe urinary tract obstruction and clinically significant urinary tract anomalies among the heterogeneous universe of patients. Congenital uropathies are frequent causes of pediatric chronic kidney disease (CKD. Imaging techniques clearly contribute to this purpose; however, sometimes, these exams are invasive, very expensive, and not sufficient to precisely define the best approach as well as the prognosis. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric urological diseases. In this regard, recent studies suggest a role for cytokines and chemokines in the pathophysiology of CAKUT and for the progression to CKD. Some authors proposed that the evaluation of these inflammatory mediators might help the management of postnatal uropathies and the detection of patients with high risk to developed chronic kidney disease. Therefore, the aim of this paper is to revise general aspects of cytokines and the link between cytokines, CAKUT, and CKD by including experimental and clinical evidence.

  9. Metoprolol Reduces Proinflammatory Cytokines and Atherosclerosis in ApoE−/− Mice

    Directory of Open Access Journals (Sweden)

    Marcus A. Ulleryd

    2014-01-01

    Full Text Available A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE−/− mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE−/− mice were treated with metoprolol (2.5 mg/kg/h or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P<0.05 versus Control. Further, metoprolol reduced serum TNFα and the chemokine CXCL1 (P<0.01 versus Control for both as well as decreasing the macrophage content in the plaques (P<0.01 versus Control. Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE−/− mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNFα and CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect.

  10. Type-1-cytokines synergize with oncogene inhibition to induce tumor growth arrest

    Science.gov (United States)

    Acquavella, Nicolas; Clever, David; Yu, Zhiya; Roelke-Parker, Melody; Palmer, Douglas C.; Xi, Liqiang; Pflicke, Holger; Ji, Yun; Gros, Alena; Hanada, Ken-ichi; Goldlust, Ian S.; Mehta, Gautam U.; Klebanoff, Christopher A.; Crompton, Joseph G.; Sukumar, Madhusudhanan; Morrow, James J.; Franco, Zulmarie; Gattinoni, Luca; Liu, Hui; Wang, Ena; Marincola, Francesco; Stroncek, David F.; Lee, Chyi-Chia R.; Raffeld, Mark; Bosenberg, Marcus W.; Roychoudhuri, Rahul; Restifo, Nicholas P.

    2014-01-01

    Both targeted inhibition of oncogenic driver mutations and immune-based therapies show efficacy in treatment of patients with metastatic cancer but responses can be either short-lived or incompletely effective. Oncogene inhibition can augment the efficacy of immune-based therapy but mechanisms by which these two interventions might cooperate are incompletely resolved. Using a novel transplantable BRAFV600E-mutant murine melanoma model (SB-3123), we explore potential mechanisms of synergy between the selective BRAFV600E inhibitor vemurafenib and adoptive cell transfer (ACT)-based immunotherapy. We found that vemurafenib cooperated with ACT to delay melanoma progression without significantly affecting tumor infiltration or effector function of endogenous or adoptively transferred CD8+ T cells as previously observed. Instead, we found that the T-cell cytokines IFNγ and TNFα synergized with vemurafenib to induce cell-cycle arrest of tumor cells in vitro. This combinatorial effect was recapitulated in human melanoma-derived cell lines and was restricted to cancers bearing a BRAFV600E-mutation. Molecular profiling of treated SB-3123 indicated that the provision of vemurafenib promoted the sensitization of SB-3123 to the anti-proliferative effects of T-cell effector cytokines. The unexpected finding that immune cytokines synergize with oncogene inhibitors to induce growth arrest have major implications for understanding cancer biology at the intersection of oncogenic and immune signaling and provides a basis for design of combinatorial therapeutic approaches for patients with metastatic cancer. PMID:25358764

  11. Leukocyte inclusion within a platelet rich plasma-derived fibrin scaffold stimulates a more pro-inflammatory environment and alters fibrin properties.

    Directory of Open Access Journals (Sweden)

    Eduardo Anitua

    Full Text Available One of the main differences among platelet-rich plasma (PRP products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF and leukocyte-platelet rich plasma (L-PRP scaffolds was determined by enzyme-linked immunosorbent assay (ELISA and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions.

  12. High efficiency cell-specific targeting of cytokine activity

    Science.gov (United States)

    Garcin, Geneviève; Paul, Franciane; Staufenbiel, Markus; Bordat, Yann; van der Heyden, José; Wilmes, Stephan; Cartron, Guillaume; Apparailly, Florence; de Koker, Stefaan; Piehler, Jacob; Tavernier, Jan; Uzé, Gilles

    2014-01-01

    Systemic toxicity currently prevents exploiting the huge potential of many cytokines for medical applications. Here we present a novel strategy to engineer immunocytokines with very high targeting efficacies. The method lies in the use of mutants of toxic cytokines that markedly reduce their receptor-binding affinities, and that are thus rendered essentially inactive. Upon fusion to nanobodies specifically binding to marker proteins, activity of these cytokines is selectively restored for cell populations expressing this marker. This ‘activity-by-targeting’ concept was validated for type I interferons and leptin. In the case of interferon, activity can be directed to target cells in vitro and to selected cell populations in mice, with up to 1,000-fold increased specific activity. This targeting strategy holds promise to revitalize the clinical potential of many cytokines.

  13. Immunologic characteristics of cytokines in otitis media with effusion.

    Science.gov (United States)

    Himi, T; Suzuki, T; Kodama, H; Takezawa, H; Kataura, A

    1992-10-01

    Levels of cytokines, interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in samples of the middle ear effusions (MEEs) from 144 ears with otitis media with effusion (OME) by enzyme-linked immunosorbent assay, followed by cytologic analysis. Middle ear effusions of the acute purulent type contained a significantly higher concentration of cytokines compared with normal control sera (p chronic stage of MEE showed higher levels of TNF than IL-1 and GM-CSF. Meanwhile, IL-1 beta showed significantly higher concentrations in acute purulent types than in serous and mucoid types (p otitis media but also with chronic otitis media. This study showed that cytokines, especially IL-1 beta, contribute to infiltration into the middle ear by inflammatory cells. This implies that the persistent presence of cytokines in MEE could be a factor in prolonged OME. PMID:1416648

  14. Morphine reduces local cytokine expression and neutrophil infiltration after incision

    Directory of Open Access Journals (Sweden)

    Li Xiangqi

    2007-10-01

    Full Text Available Abstract Background Inflammation and nociceptive sensitization are hallmarks of tissue surrounding surgical incisions. Recent studies demonstrate that several cytokines may participate in the enhancement of nociception near these wounds. Since opioids like morphine interact with neutrophils and other immunocytes, it is possible that morphine exerts some of its antinociceptive action after surgical incision by altering the vigor of the inflammatory response. On the other hand, keratinocytes also express opioid receptors and have the capacity to produce cytokines after injury. Our studies were directed towards determining if opioids alter cytokine production near incisions and to identify cell populations responsible for producing these cytokines. Results A murine incisional model was used to measure the effects of acute morphine administration (0.1–10 mg/kg on nociceptive thresholds, neutrophil infiltration and cytokine production in hind paw skin 30 minutes and 2 hours after incision. Incised hind paws displayed profound allodynia which was reduced by morphine (0.1–10 mg/kg in the 2 hours following incision. Skin samples harvested from these mice showed enhanced levels of 5 cytokines: IL-1β, IL-6, tumor necrosis factor alpha (TNFα, granulocyte colony stimulating factor (G-CSF and keratinocyte-derived cytokine (KC. Morphine reduced these incision-stimulated levels. Separate analyses measuring myeloperoxidase (MPO and using immunohistochemistry demonstrated that morphine dose-dependently reduced the infiltration of neutrophils into the peri-incisional tissue. The dose of morphine required for reduction of cytokine accumulation, however, was below that required for inhibition of peri-incisional neutrophil infiltration. Additional immunohistochemical studies revealed wound edge keratinocytes as being an important source of cytokines in the acute phase after incision. Conclusion Acute morphine administration of doses as low as 0.1 mg/kg reduces

  15. Routes to Transplant Tolerance versus Rejection: The Role of Cytokines

    OpenAIRE

    Walsh, Patrick T.; Strom, Terry B.; Turka, Laurence A.

    2004-01-01

    The alloimmune response can be divided into specific junctures where critical decisions between tolerance and immunity are made which define the outcome of the transplant. At these “decision nodes” various cytokines direct alloresponsive T cells to develop either a proinflammatory response aimed at graft destruction or an immunoregulatory response facilitating graft acceptance. This review will focus on the role of these cytokines in influencing the progression of an alloimmune response leadi...

  16. Expression of Secreted Cytokine and Chemokine Inhibitors by Ectromelia Virus

    OpenAIRE

    Smith, Vincent P.; Alcami, Antonio

    2000-01-01

    The production of secreted proteins that bind cytokines and block their activity has been well characterized as an immune evasion strategy of the orthopoxviruses vaccinia virus (VV) and cowpox virus (CPV). However, very limited information is available on the expression of similar cytokine inhibitors by ectromelia virus (EV), a virulent natural mouse pathogen that causes mousepox. We have characterized the expression and binding properties of three major secreted immunomodulatory activities i...

  17. In situ expression of cytokines in human heart allografts.

    OpenAIRE

    van Hoffen, E; van Wichen, D.; Stuij, I.; de Jonge, N.; Klöpping, C.; Lahpor, J.; Van Den Tweel, J.; Gmelig-Meyling, F.; Weger, R. de

    1996-01-01

    Although allograft rejection, the major complication of human organ transplantation, has been extensively studied, little is known about the exact cellular localization of the cytokine expression inside the graft during rejection. Therefore, we used in situ hybridization and immunohistochemistry to study local cytokine mRNA and protein expression in human heart allografts, in relation to the phenotypical characteristics of the cellular infiltrate. Clear expression of mRNA for interleukin (IL)...

  18. Inflammatory cytokines in degeneration, regeneration and maintenance of sciatic nerve

    OpenAIRE

    Yokoyama, Shigeru

    2011-01-01

    Inflammatory cytokines play important roles in a variety of pathophysiological changes associated with traumatic injury and demyelinating disorders in the peripheral nervous system. After sciatic nerve injury, proinflammatory cytokines such as interleukin 1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) are produced by and act on neurons, Schwann cells, and infiltrating inflammatory cells at the lesion site. Underlying these processes is receptor-mediated activation of intr...

  19. Role of cytokines in myocardial ischemia and reperfusion

    Directory of Open Access Journals (Sweden)

    H. S. Sharma

    1997-01-01

    Full Text Available Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia–reperfusion injury. Furthermore, ischemia–reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6 which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-α (TNF-α, transforming growth factor-β1 (TGF-β1 as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF, in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-α may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart.

  20. Characterization of cytokines present in middle ear effusions.

    Science.gov (United States)

    Yellon, R F; Leonard, G; Marucha, P T; Craven, R; Carpenter, R J; Lehmann, W B; Burleson, J A; Kreutzer, D L

    1991-02-01

    Retention of inflammatory mediators and cells in the middle ear cleft during chronic otitis media with effusion (COME), results in ongoing inflammation with the potential for pathologic changes and hearing loss. Cytokines are glycoproteins produced by macrophages and other cells. Activities of cytokines include fever production, osteoclast, fibroblast, phagocyte and cytotoxic cell activation, regulation of antibody formation, and inhibition of cartilage, bone and endothelial cell growth. Using enzyme-linked immunospecific assays we measured levels of six cytokines in middle ear effusions (MEE) from children with COME. Significant levels of four cytokines: interleukin-1-beta (greater than 50 pg/ml), interleukin-2 (greater than 300 pg/ml), tumor necrosis factor-alpha (greater than 40 pg/ml), and gamma-interferon (greater than 6.25 pg/ml) were found in 51%, 54%, 63%, and 19% of MEE, respectively. In contrast, levels of a fifth cytokine, granulocyte-macrophage colony-stimulating factor, and a sixth cytokine, interleukin-4, were undetectable. Age was observed to have a significant effect on the levels of specific cytokines. Interleukin-1 (IL-1) correlated inversely (P less than .02) with age such that the younger the child, the higher the level of IL-1 in MEE. Tumor necrosis factor-alpha (TNF) correlated directly (P less than .005) with age such that the older the child, the higher the level of TNF in MEE. Children undergoing tympanostomy on multiple occasions had average MEE TNF levels (234.2 +/- 109.1 pg/mg total protein) that were nearly 14 times higher (P less than .005) than those from children undergoing their first tympanostomy (16.9 +/- 3.0 pg/mg total protein). Thus IL-1 correlated with the early stages of COME, while TNF correlated with persistence of disease. The presence of these cytokines in MEE may be responsible for the mucosal damage, bone erosion, fibrosis, and resulting hearing loss seen in some cases of COME. PMID:1992267

  1. Cytokine signatures of human whole blood for monitoring immunosuppression

    OpenAIRE

    He, Yi; Luo, Yuwei; Lao, Xiaobin; Tan, Liping; Sun, Erwei

    2014-01-01

    How to evaluate status of the immune system is extremely critical for clinical immunosuppressive treatment. In this study, we tested the secretion of cytokines in undiluted whole blood samples stimulated with Phorbol 12-myristate 13-acetate (PMA) and ionomycin (IONO), and compared the effects of dexamethasone (DEX), cyclosporine A (CsA) or mycophenolic acid (MPA), either alone or in combination, on cytokine profiles. The results showed that both DEX and CsA dose-dependently inhibited the prod...

  2. Cytokines in the systemic inflammatory response syndrome: a review

    OpenAIRE

    Jaffer, U; Wade, R G; Gourlay, T

    2010-01-01

    Introduction Patients subject to major surgery, suffering sepsis, major trauma, or following cardiopulmonary bypass exhibit a systemic inflammatory response. This inflammatory response involves a complex array of inflammatory polypeptide molecules known as cytokines. It is well accepted that the loss of local control of the release of these cytokines leads to systemic inflammation and potentially deleterious consequences including the Systemic Inflammatory Response Syndrome, Multi-Organ Dysfu...

  3. Aspergillus fumigatus Conidial Melanin Modulates Host Cytokine Response

    OpenAIRE

    Chai, Louis; Netea, Mihai; SUGUI, JANYCE; Vonk, Alieke; van de Sande, Wendy; Warris, Adilia; Kwon-Chung, Kyung; Jan Kullberg, Bart

    2009-01-01

    textabstractMelanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced cytokine response. The albino conidia induced significantly more proinflammatory cytokines in human peripheral blood mononuclear cells (PBMC), as compared to melanised wild-type conidia. Blocking ...

  4. Assessment by Flow Cytometry of Cytokine Production in Malnourished Children

    OpenAIRE

    Rodríguez, Leonor; González, Cristina; Flores, Luis; Jiménez-Zamudio, Luis; Graniel, Jaime; Ortiz, Rocío

    2005-01-01

    Malnutrition in children is associated with an increased risk of infection and death. Multiple abnormalities in the immune response, including cytokine production, in protein energy-malnourished children have been described and could account for the increased severity and frequency of infections. In this study, we used flow cytometry to investigate the effects of malnutrition on the production of cytokines (interleukin-2 [IL-2], gamma interferon [IFN-γ], IL-4, and IL-10) in CD4+ and CD8+ cell...

  5. A Review: Inflammatory Process in Alzheimer's Disease, Role of Cytokines

    OpenAIRE

    Jose Miguel Rubio-Perez; Juana Maria Morillas-Ruiz

    2012-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder to date. Neuropathological hallmarks are β -amyloid (A β ) plaques and neurofibrillary tangles, but the inflammatory process has a fundamental role in the pathogenesis of AD. Inflammatory components related to AD neuroinflammation include brain cells such as microglia and astrocytes, the complement system, as well as cytokines and chemokines. Cytokines play a key role in inflammatory and anti-inflammatory processes in AD. ...

  6. Vitamin D and Serum Cytokines in a Randomized Clinical Trial

    OpenAIRE

    Eleanor Yusupov; Melissa Li-Ng; Simcha Pollack; James K. Yeh; Mageda Mikhail; Aloia, John F

    2010-01-01

    Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines. Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]....

  7. Ex vivo and in vitro production of pro-inflammatory cytokines in Blau syndrome

    Directory of Open Access Journals (Sweden)

    P. Galozzi

    2015-03-01

    Full Text Available The objective was to study both ex vivo and in vitro secretion of pro-inflammatory cytokines in patients affected by Blau syndrome (BS and carrying p.E383K mutation in the CARD15/NOD2 gene associated with the disease. For ex vivo studies, peripheral blood mononuclear cells (PBMCs, serum from three patients and healthy controls have been collected. PBMCs have been cultured in the presence or absence of inflammatory enhancers, such as lipopolysaccharide (LPS and muramyl dipeptide (MDP. The levels of interleukin (IL-1β, IL-6, IL-8, tumor necrosis factor (TNF-α and interferon (IFN-γ were assayed by either immunoassay or array-based system. For in vitro studies, different constructs were created cloning human wild-type and p.E383K-mutated NOD2 cDNA into the expression vector pCMV-Tag2c. HEK293 cell lines were stably transfected, cultured with or without MDP and IL-8 level was assayed in their surnatants. Statistical analysis in both studies was performed using non-parametric tests. Both ex vivo and in vitro studies have not identified a significant increase in secretion of the analyzed proinflammatory cytokines. p.E383K-mutated NOD2 transfected cells express low level of IL-8. The ex vivo basal level results from both serum and PBMCs surnatants present similar levels of IL-1β, IL-6, TNF-α and IFN-γ in patients and controls. The presence of the stimulant agents (LPS and MDP, either individual or paired, does not lead to significant increases in all cytokines concentrations in patients compared to controls. Taken together, the ex vivo and in vitro data suggest that there is not a primary mediation of IL-1β and other pro-inflammatory cytokines in BS patients carrying p.E383K.

  8. ACUTE PHASE PROTEINS, LIPID PROFILE AND PROINFLAMMATORY CYTOKINES IN HEALTHY AND BRONCHOPNEUMONIC WATER BUFFALO CALVES

    Directory of Open Access Journals (Sweden)

    Sabry M. El-Bahr

    2013-01-01

    Full Text Available The aim of the present study was to evaluate the diagnostic value of Acute Phase Proteins (APP, lipid profiles and proinflammatory cytokines in healthy and bronchopneumonic water buffalo calves. Therefore, sixty water buffalo calves (9±1 month old, 175±15 kg were divided into two equal groups, the first group represented healthy, control, calves whereas calves of the second group were affected with bronchopneumonia. Total leukocytic and differential counts were determined. Serum total protein, albumin, Triacylglyceol (TAG, low density lipoprotein cholesterol (LDL-c, High Density Lipoprotein cholesterol (HDL-c, Total cholesterol, Alanine Amino Transferase (ALT, Aspartate Amino Transferase (AST, Alkaline Phosphatase (ALP, Fibrinogen (Fb, Haptaglobin (Hp, Serum Amyloid A (SAA, Tumor Necrosis Factor-alpha (TNF-α, Interleukins (IL1β, IL-12 and Interferon-gamma (IFN-γ were also determined. In addition, Bronchoalveolar Lavage (BAL was collected and analyzed. The present findings indicated that, total leukocytic and neutrophils counts were significantly (p<0.05 higher in pneumonic water buffalo calves compare with control. The examined biochemical parameters were significantly (p<0.05 increased in pneumonic calves except for total protein, albumin, cholesterol and HDL-c which were significantly (p<0.05 lower compare with control. Serum concentrations of investigated APP and proinflammatory cytokines were significantly (p<0.05 higher in pneumonic water buffalo calves than those of control. The present study demonstrated that, APP, lipid profile and proinflammatory cytokines perhaps served as biomarkers of bronchopneumonia in water buffalo calves. However, future studies with higher baseline sampling are still needed to establish and validate reference values for APP and cytokines in water buffalo calves.

  9. Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production

    Directory of Open Access Journals (Sweden)

    Longo Dan L

    2011-03-01

    Full Text Available Abstract Background Intermittent fasting (IF improves healthy lifespan in animals by a mechanism involving reduced oxidative damage and increased resistance to stress. However, no studies have evaluated the impact of controlled meal frequency on immune responses in human subjects. Objective A study was conducted to establish the effects of controlled diets with different meal frequencies, but similar daily energy intakes, on cytokine production in healthy male and female subjects. Design In a crossover study design with an intervening washout period, healthy normal weight middle-age male and female subjects (n = 15 were maintained for 2 months on controlled on-site one meal per day (OMD or three meals per day (TMD isocaloric diets. Serum samples and peripheral blood mononuclear cells (PBMCs culture supernatants from subjects were analyzed for the presence of inflammatory markers using a multiplex assay. Results There were no significant differences in the inflammatory markers in the serum of subjects on the OMD or TMD diets. There was an increase in the capacity of PBMCs to produce cytokines in subjects during the first month on the OMD or TMD diets. Lower levels of TNF-α, IL-17, MCP-1 and MIP-1β were produced by PBMCs from subjects on the OMD versus TMD diet. Conclusions PBMCs of subjects on controlled diets exhibit hypersensitivities to cellular stimulation suggesting that stress associated with altered eating behavior might affect cytokine production by immune cells upon stimulation. Moreover, stimulated PBMCs derived from healthy individuals on a reduced meal frequency diet respond with a reduced capability to produce cytokines.

  10. Differential cytokine regulation by NF-κB and AP-1 in Jurkat T-cells

    Directory of Open Access Journals (Sweden)

    Jass Jana

    2010-05-01

    Full Text Available Abstract Background Activator protein (AP-1 and nuclear factor (NF-κB largely control T-cell activation, following binding of foreign antigens to the T-cell receptor leading to cytokine secretion. Elevated levels of pro-inflammatory cytokines and chemokines such as TNF, IL-6 and CXCL8 are associated with several human diseases including cystic fibrosis, pulmonary fibrosis and AIDS. The aim of this study was to investigate the role of the transcription factors, AP-1 and NF-κB, in IL-6 and CXCL8 regulation in Jurkat T-cells. Results Phorbol myristate acetate (PMA exposure resulted in an up-regulation of AP-1 and down-regulation of NF-κB activity, however, exposure to heat killed (HK Escherichia. coli MG1655 resulted in a dose-dependent increase in NF-κB activity without affecting AP-1. The cytokine profile revealed an up-regulation of the chemokine CXCL8 and the pro-inflammatory cytokines TNF, IL-2 and IL-6 following treatment with both PMA and HK E. coli, while the levels of the anti-inflammatory cytokine IL-10 were not affected by PMA but were significantly down-regulated by HK E. coli. AP-1 activation was significantly increased 2 h after PMA exposure and continued to increase thereafter. In contrast, NF-κB responded to PMA exposure by a rapid up-regulation followed by a subsequent down-regulation. Increased intracellular Ca2+ concentrations countered the down-regulation of NF-κB by PMA, while similar treatment with calcium ionophore resulted in a reduced NF-κB activity following induction with HK E. coli. In order to further study NF-κB activation, we considered two up-stream signalling proteins, PKC and Bcl10. Phosphorylated-PKC levels increased in response to PMA and HK E. coli, while Bcl10 levels significantly decreased following PMA treatment. Using an NF-κB activation inhibitor, we observed complete inhibition of IL-6 expression while CXCL8 levels only decreased by 40% at the highest concentration. Treatment of Jurkat T

  11. Cytokine and Immuno-Gene Therapy for Solid Tumors

    Institute of Scientific and Technical Information of China (English)

    Chuan-YuanLi; QianHuang; Hsiang-FuKung

    2005-01-01

    Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possibility to mobilize the body's own immune system to eradicate cancer not only locally but also systemically. Since its initial discovery, cytokine-based immunotherapy has been vigorously and extensively investigated for cancer treatment due to the perception of it as a relatively easily purifiable, injectable form of cancer treatment agent. However, so far most cytokine-based therapy trials have fallen short ofexpectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity. The emergence of novel gene therapy approach to deliver therapeutic cytokine to tumors locally generated great excitement since it has the potential of generating sustained high local concentration of immunostimulatory cytokine without raising the systemic levels of the cytokines, which is responsible for most of the observed toxicity. In this review, we will attempt to provide an overview of the field and discuss some of the problems associated with cytokine-based immuno-gene therapy and potential solutions. Cellular & Molecular Immunology. 2005;2(2):81-91.

  12. Cytokine and Immuno-Gene Therapy for Solid Tumors

    Institute of Scientific and Technical Information of China (English)

    Chuan-Yuan Li; Qian Huang; Hsiang-Fu Kung

    2005-01-01

    Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possibility to mobilize the body's own immune system to eradicate cancer not only locally but also systemically. Since its initial discovery, cytokine-based immunotherapy has been vigorously and extensively investigated for cancer treatment due to the perception of it as a relatively easily purifiable, injectable form of cancer treatment agent. However, so far most cytokine-based therapy trials have fallen short of expectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity. The emergence of novel gene therapy approach to deliver therapeutic cytokine to tumors locally generated great excitement since it has the potential of generating sustained high local concentration of immunostimulatory cytokine without raising the systemic levels of the cytokines, which is responsible for most of the observed toxicity. In this review, we will attempt to provide an overview of the field and discuss some of the problems associated with cytokine-based immuno-gene therapy and potential solutions.Cellular & Molecular Immunology. 2005;2(2):81-91.

  13. Temporal Regulation of Cytokines by the Circadian Clock

    Directory of Open Access Journals (Sweden)

    Atsuhito Nakao

    2014-01-01

    Full Text Available Several parameters of the immune system exhibit oscillations with a period of approximately 24 hours that refers to “circadian rhythms.” Such daily variations in host immune system status might evolve to maximize immune reactions at times when encounters with pathogens are most likely to occur. However, the mechanisms behind circadian immunity have not been fully understood. Recent studies reveal that the internal time keeping system “circadian clock” plays a key role in driving the daily rhythms evident in the immune system. Importantly, several studies unveil molecular mechanisms of how certain clock proteins (e.g., BMAL1 and CLOCK temporally regulate expression of cytokines. Since cytokines are crucial mediators for shaping immune responses, this review mainly summarizes the new knowledge that highlights an emerging role of the circadian clock as a novel regulator of cytokines. A greater understanding of circadian regulation of cytokines will be important to exploit new strategies to protect host against infection by efficient cytokine induction or to treat autoimmunity and allergy by ameliorating excessive activity of cytokines.

  14. INVESTIGATION OF CYTOKINE PROFILE IN PATIENTS WITH REACTIVE ARTHRITIS

    Directory of Open Access Journals (Sweden)

    T. V. Gaponova

    2008-01-01

    Full Text Available Abstract. Pathogenesis of reactive arthritis (ReA is not clear yet. Several trials suggest that increased production of proinflammatory cytokines is responsible for development of arthritis in ReA, while other studies report that Th1 cytokine response in ReA is impaired in favor of Th2 response. The aim of our study was to investigate serum levels of cytokines IL-1β, IL-4, IL-6, TNFα, IFNγ and IL-1Ra in the patients with ReA of different etiology, as compared with infection-related arthritis. The results of our study had demonstrated that serum levels of IL-1β and TNFα in the patients with ReA were significantly higher, whereas IL-1Ra, IL-4, IL-6 proved to be significantly lower than in healthy controls. Serum levels of IL-6 were significantly higher in patients with chronic ReA, as compared to the cases of acute and recurrent ReA. No significant differences in cytokine profiles were found between the patients with ReA, and the persons with infection-related arthritis. The data obtained are, generally, suggestive for proinflammatory Th1 cytokine profile in ReA patients studied, this confirming the mostly assumed pathogenetic hypothesis for reactive arthritis where an underlying cytokine imbalance is suggested. (Med. Immunol., 2008, vol. 10, N 2-3, pp 167-172.

  15. Cytokine signaling for proliferation, survival, and death in hematopoietic cells.

    Science.gov (United States)

    Miyajima, A; Ito, Y; Kinoshita, T

    1999-04-01

    The survival, proliferation, and differentiation of hematopoietic cells are regulated by cytokines. In the absence of cytokines, hematopoietic cells not only stop proliferation, but undergo apoptosis. This strict dependency of hematopoietic cells on cytokines is an important mechanism that maintains the homeostasis of blood cells. Cytokines induce various intracellular signaling pathways by activating the receptor-associated Janus kinases (Jaks), and distinct signals are responsible for cell cycle progression and cell survival. Induction of signals for cell cycle progression without suppressing apoptosis results in apoptotic cell death, indicating the essential role of anti-apoptotic signaling for cell growth. In hematopoietic cells, Ras, a cellular protooncogen product, and phosphatidylinositol 3 kinase are involved in the suppression of apoptosis. Cytokine depletion not only turns off anti-apoptotic signaling, but also actively induces cell death by activating caspases, a distinct family of cysteine proteases. Alterations in the mechanisms of cytokine signaling for cell cycle progression and anti-apoptotic function are implicated in hematological disorders. PMID:10222650

  16. A genetically encoded bioluminescent indicator for illuminating proinflammatory cytokines.

    Science.gov (United States)

    Kim, Sung Bae; Ozawa, Takeaki; Umezawa, Yoshio

    2016-01-01

    We introduce a method to evaluate the activities of cytokines based on the nuclear transport of NF-κB. A pair of bioluminescent indicators was made for conferring cytokine sensitivity to cervical carcinoma-derived HeLa cells. The principle is based on reconstitution of split fragments of Renilla reniformis luciferase (RLuc) by protein splicing with a DnaE intein from Synechocystis sp. PCC6803. The bioluminescence intensity of thus reconstituted RLuc in the HeLa cells was used as a measure of the activities for cytokines. With the present method, we evaluated the activities of various cytokines based on the nuclear transport of NF-κB in human cervical carcinoma-derived HeLa cells carrying the indicators. The present approach to evaluating the activities of cytokines may provide a potential clinical value in monitoring drug activity and directing treatment for various diseases related with NF-κB. The method highlights the experimental procedure from our original publications, Anal. Biochem. 2006, 359, 147-149 and Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 11542. The summary of the method is: •Cytokine activities are determined within 2 h after stimulation.•Temporarily inactivated split-luciferase fragments are reconstituted by protein splicing.•Nucleartrafficking of NF-κB was illuminated for gauging the ligand-driven activity. PMID:27489781

  17. Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy

    Directory of Open Access Journals (Sweden)

    Jeffry Cutrera

    2013-01-01

    Full Text Available The safest and most effective cytokine therapies require the favorable accumulation of the cytokine in the tumor environment. While direct treatment into the neoplasm is ideal, systemic tumor-targeted therapies will be more feasible. Electroporation-mediated transfection of cytokine plasmid DNA including a tumor-targeting peptide-encoding sequence is one method for obtaining a tumor-targeted cytokine produced by the tumor-bearing patient’s tissues. Here, the impact on efficacy of the location of targeting peptide, choice of targeting peptide, tumor histotype, and cytokine utilization are studied in multiple syngeneic murine tumor models. Within the same tumor model, the location of the targeting peptide could either improve or reduce the antitumor effect of interleukin (IL12 gene treatments, yet in other tumor models the tumor-targeted IL12 plasmid DNAs were equally effective regardless of the peptide location. Similarly, the same targeting peptide that enhances IL12 therapies in one model fails to improve the effect of either IL15 or PF4 for inhibiting tumor growth in the same model. These interesting and sometimes contrasting results highlight both the efficacy and personalization of tumor-targeted cytokine gene therapies while exposing important aspects of these same therapies which must be considered before progressing into approved treatment options.

  18. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan; Claesson, Mogens; Nielsen, Hans; Rosenberg, Jacob

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction of......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....... responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior to...

  19. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Claesson, Mogens Helweg; Nielsen, Hans J; Rosenberg, Jacob

    2009-01-01

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction of......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....... responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior to...

  20. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    Recently, in human geography there has been a considerable attention paid to retheorising maps; less as a product and more as practice. This refers to the notion that rather than reading maps as fixed representations, digital mapping is by nature a dynamic, performative, and participatory practice....... In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology...

  1. Probiotic Lactobacillus casei and paracasei strains affect production of cytokines towards anti-allergic response

    Czech Academy of Sciences Publication Activity Database

    Kozáková, Hana; Schwarzer, Martin; Doušková, Dagmar; Hudcovic, Tomáš; Cukrowska, B.

    Kysucke Nove Mesto: Pamida International, 2010. s. 37-38. ISBN 978-80-970168-4-5 R&D Projects: GA AV ČR IAA500200710; GA MŠk 2B06053; GA ČR GA303/09/0449 Institutional research plan: CEZ:AV0Z50200510 Keywords : allergy * mouse model Subject RIV: EC - Immunology

  2. Psychological distress and SSRI use predict variation in inflammatory cytokines during pregnancy

    OpenAIRE

    2013-01-01

    Evidence supports the premise that maternal psychological distress adversely affects pregnancy outcomes and that inflammatory markers and placentally-produced corticotrophin-releasing hormone (pCRH) are likely mediating factors. The primary aim of the study was to explore the associations between maternal psychological distress, use of selective serotonin re-uptake inhibitors, pCRH, and maternal plasma inflammatory markers during pregnancy. Measures of maternal plasma pCRH, Interleukins-1, 6,...

  3. Plasma waves

    CERN Document Server

    Swanson, DG

    1989-01-01

    Plasma Waves discusses the basic development and equations for the many aspects of plasma waves. The book is organized into two major parts, examining both linear and nonlinear plasma waves in the eight chapters it encompasses. After briefly discussing the properties and applications of plasma wave, the book goes on examining the wave types in a cold, magnetized plasma and the general forms of the dispersion relation that characterize the waves and label the various types of solutions. Chapters 3 and 4 analyze the acoustic phenomena through the fluid model of plasma and the kinetic effects. Th

  4. Plasma astrophysics

    CERN Document Server

    Kaplan, S A; ter Haar, D

    2013-01-01

    Plasma Astrophysics is a translation from the Russian language; the topics discussed are based on lectures given by V.N. Tsytovich at several universities. The book describes the physics of the various phenomena and their mathematical formulation connected with plasma astrophysics. This book also explains the theory of the interaction of fast particles plasma, their radiation activities, as well as the plasma behavior when exposed to a very strong magnetic field. The text describes the nature of collective plasma processes and of plasma turbulence. One author explains the method of elementary

  5. Identification of enhanced cytokine generation following sepsis. Dream of magic bullet for mortality prediction and therapeutic evaluation

    Directory of Open Access Journals (Sweden)

    H Hamishehkar

    2010-09-01

    Full Text Available "n  "nBackground and the purpose of the study: sepsis is one of the most widespread and lethal disease in Intensive Care Units (ICU. Based on pathophisyology of sepsis, it seems that routine laboratory tests combined with analysis of pro-inflammatory cytokines plasma levels, help clinicians to have more information about disease progress and its correct management. "nMethods:This was a prospective observational study to determine the predictive role of Tumor Necrosis Factor alpha (TNF-α, Interleukin (IL-1β and IL-6 as three main pro-inflammatory cytokines and Acute Physiology and Chronic Health Evaluation (APACHE II and Sequential Organ Failure Assessment (SOFA as two scoring systems in mortality of critically ill patients with severe sepsis. Fifty and five patients with criteria of severe sepsis were included in this study. An exclusion criterion was post Cardiopulmonary Resuscitation (CPR status. Cytokines (TNF-α, IL-1β and IL-6 were assayed in the first, third and seventh days in blood of patients. Results and major conclusion:Among three measured cytokines, sequential levels of TNF-α and IL-6 showed significant differences between survivors and nonsurvivors. IL-6 had a good correlation with outcome and scoring systems during the period of this study. The areas under the receiver operating characteristic (AUROC curve indicated that APACHE II (0.858, 0.848, 0.861 and IL-6 (0.797, 0.799, 0.899 had discriminative power in prediction of mortality during sequental measured days. Multiple logestic regression analysis identified that evaluation of APACHE II and TNF-α in the first day and APACHE II and IL-6 in the third and seventh days of severe septic patients are independent outcome predictors. Results of this study suggest that IL-6 and APACHE II are useful cytokine and scoring systems respectively in prediction of mortality and clinical evaluation of severe septic patients.

  6. Proinflammatory and anti-inflammatory cytokines in adolescents from Southeast Bulgarian cities with different levels of air pollution.

    Science.gov (United States)

    Dobreva, Zlatka Georgieva; Kostadinova, Gergana Stoianova; Popov, Borislav Nikolov; Petkov, Georgi Stefanov; Stanilova, Spaska Angelova

    2015-12-01

    Epidemiological studies demonstrated that the exposure of different air pollutants including particulate matter (PM) has been related to adverse effect on immune system. Current study was designed to investigate cytokines in blood plasma of adolescent persons continuously exposed to different degrees of ambient air pollutions. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), IL-12p40, and IL-10 were chosen as cytokines of proinflammatory and anti-inflammatory immune response. The peripheral venous blood was taken from adolescents living in the cities of Stara Zagora region, Southeast Bulgaria, that is, in Stara Zagora, Kazanlak, and Chirpan. The quantity of cytokines in plasma samples was determined by enzyme-linked immunosorbent assay. Results demonstrated that youths living in Stara Zagora showed significantly smaller quantity of TNF-α, compared with adolescents from Kazanlak and Chirpan. Moreover, adolescents living in Stara Zagora showed significantly higher quantity of IL-10 than students from Kazanlak and Chirpan. Analysis of the data of air quality gives reason to assert that PM10 and PM2.5 have been the main atmospheric pollutants around the monitoring points. The complex air quality assessment based on these criteria determined that the highest air pollution was in the city of Stara Zagora, followed by Chirpan and the relatively unpolluted town was Kazanlak. We concluded that air pollutants, mostly PM2.5, can modulate cytokine production and can change the balance between proinflammatory TNF-α and anti-inflammatory IL-10 production. Increased levels of IL-10 combined with decreased level of TNF-α in adolescents living in Stara Zagora can serve as a biomarker for suppression of T helper 1 (Th1) cell-mediated immunity and exacerbation of Th2 humoral immune response and could be a prerequisite for the development of allergic and autoimmune diseases. PMID:23771874

  7. Cytokines Expression Profile and Kinetics of Peste des petits ruminants Virus Antigen and Antibody in Infected and Vaccinated Goats

    Institute of Scientific and Technical Information of China (English)

    Arun Patel; Kaushal Kishor Rajak; Vinayagamurthy Balamurugan; Arnab Sen; Shashi Bhusan Sudhakar; Veerakyathappa Bhanuprakash; Raj Kumar Singh; Awadh Bihari Pandey

    2012-01-01

    The present study deals with the co-ordination of cytokine(IL-4 and IFN-γ) expression and kinetics of peste des petits ruminants(PPR) virus antigen and antibody in PPRV infected and vaccinated goats.The infected animals exhibited mixed cytokine(both TH1 and TH2) responses in the initial phase of the disease.The infected and dead goats had increased IFN-γ response before their death; while IL-4 remained at the base level.The cytokine expression in recovered animals was almost similar to that of vaccinated ones,where a unique biphasic response of IL-4 expression was observed with an up-regulation of IFN-γ on 7th days post vaccination(dpv).Analysis of PPR virus antigen and antibody kinetics in different components of blood from infected and vaccinated animals revealed that the PPR virus antigen load was highest in plasma followed by serum and blood of the infected animals,whereas vaccinated animals showed only marginal positivity on 9th dpv.The antibody titer was high in serum followed by plasma and blood in both vaccinated and infected animals.Therefore,it is inferred that the presence of antigen and antibody were significant with the expression of cytokine,and that a decreased response of IL-4 was noticed during intermediate phase of the disease i.e.,7 to 12th days post infection(dpi).This indicates the ability to mount a functional TH2 response after 14th dpi could be a critical determinant in deciding the survival of the PPR infected animal.

  8. Increased circulating pro-inflammatory cytokines and imbalanced regulatory T-cell cytokines production in chronic idiopathic urticaria.

    Science.gov (United States)

    Dos Santos, Juliana Cristina; Azor, Mayce Helena; Nojima, Viviane Yoshimi; Lourenço, Francinelson Duarte; Prearo, Erica; Maruta, Celina Wakisaka; Rivitti, Evandro Ararigbóia; da Silva Duarte, Alberto José; Sato, Maria Notomi

    2008-10-01

    The immunologic characterization of chronic idiopathic urticaria (CIU), mainly regarding cytokine profile needs more investigation. We examined circulating inflammatory cytokine levels, T-cell induced secretion, and cytokine mRNA expression in patients with CIU subjected to the intradermal autologous serum skin test (ASST). Increased levels of circulating pro-inflammatory cytokines, such as TNF-alpha, IL-1beta, IL-12p70, and IL-6 have been observed in most of patients with CIU, together with an enhancement of IL-2 secretion following T-cell stimulation. Highlighting the inflammatory profile in CIU found in ASST positive, is the enhanced B-cell proliferative responsiveness and increased IL-17 secretion levels. ASST-positive patients also exhibited impaired IL-4 secretion associated with increased IL-10 production. Altered cytokine expression in patients with ASST-negative, was the down-modulation of spontaneous IL-10 mRNA expression levels in peripheral blood mononuclear cells. Our findings support the concept of immunologic dysregulation in CIU, revealing a systemic inflammatory profile associated with disturbed cytokine production by T cells, mainly related to IL-17 and IL-10 production. PMID:18586117

  9. [Affective dependency].

    Science.gov (United States)

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy. PMID:23888587

  10. Do Cytokines Really Sing the Blues?

    OpenAIRE

    Raison, Charles L.; Miller, Andrew H.

    2013-01-01

    Editor’s note: The World Health Organization predicts that depression, which already affects about 10 percent of the population in the United States, will be the world’s leading medical condition by 2030. Evidence suggests several causes for depression, including traumatic life events, disease, poison, and nutritional deficiencies. Many of these causes are associated with elevated levels of inflammatory biomarkers in the blood, which may in turn lead to inflammatory changes in the brain. Our ...

  11. Plasma Science Committee (PLSC)

    International Nuclear Information System (INIS)

    The Plasma Science Committee (PLSC) is a standing committee under the auspices of the Board on Physics and Astronomy, Commission on Physical Sciences, Mathematics, and Applications of the National Academy of Sciences--National Research Council. Plasma sciences represent a broad and diverse field. The PLSC has accepted the responsibility of monitoring the continuing development and assessing the general health of the field as whole. Although select advisory bodies have been created to address specific issues that affect plasma science, such as the Fusion Policy Advisory Committee (FPAC), the PLSC provides a focus for the plasma science community that is unique and essential. The membership of the PLSC is drawn from research laboratories in universities, industry, and government. Areas of expertise on the committee include accelerators and beams, space physics, astrophysics, computational physics and applied mathematics, fusion plasmas, fundamental experiments and theory, radiation sources, low temperature plasmas, and plasma-surface interactions. The PLSC is well prepared to respond to requests for studies on specific issues. This report discusses ion of the PLSC work

  12. Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding.

    Science.gov (United States)

    Newman, K L; Moe, C L; Kirby, A E; Flanders, W D; Parkos, C A; Leon, J S

    2016-06-01

    Noroviruses (NoV) are the most common cause of epidemic gastroenteritis world-wide. NoV infections are often asymptomatic, although individuals still shed large amounts of NoV in their stool. Understanding the differences between asymptomatic and symptomatic individuals would help in elucidating mechanisms of NoV pathogenesis. Our goal was to compare the serum cytokine responses and faecal viral RNA titres of asymptomatic and symptomatic NoV-infected individuals. We tested serum samples from infected subjects (n = 26; 19 symptomatic, seven asymptomatic) from two human challenge studies of GI.1 NoV for 16 cytokines. Samples from prechallenge and days 1-4 post-challenge were tested for these cytokines. Cytokine levels were compared to stool NoV RNA titres quantified previously by reverse transcription-polymerase chain reaction (RT-qPCR). While both symptomatic and asymptomatic groups had similar patterns of cytokine responses, the symptomatic group generally exhibited a greater elevation of T helper type 1 (Th1) and Th2 cytokines and IL-8 post-challenge compared to the asymptomatic group (all P viral RNA titre was associated positively with daily IL-6 concentration and negatively with daily IL-12p40 concentration (all P viral RNA titre, duration of viral shedding or cumulative shedding. Symptomatic individuals, compared to asymptomatic, have greater immune system activation, as measured by serum cytokines, but they do not have greater viral burden, as measured by titre and shedding, suggesting that symptoms may be immune-mediated in NoV infection. PMID:26822517

  13. Plasma device

    International Nuclear Information System (INIS)

    A method is described of providing electron beam heating of a high-density plasma to drive a fast liner to implode a structured microsphere. An annular relativistic electron beam is used to heat an annular plasma to kilovolt temperatures through streaming instabilities in the plasma. Energy deposited in the annular plasma then converges on a fast liner to explosively or ablatively drive the liner to convergence to implode the structured microsphere. (U.K.)

  14. Defining an appropriate leucoreduction strategy by serial assessment of cytokine levels in platelet concentrates prepared by different methods

    Directory of Open Access Journals (Sweden)

    Daljit Kaur

    2015-01-01

    Full Text Available Background and Objectives: Different methods of platelet concentrate preparations leave behind certain number of residual leukocytes, accounting for most of the febrile nonhemolytic transfusion reactions, especially in multitransfused patients. Various inflammatory cytokines, such as tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, and IL-6 are generated during storage and have been implicated for these adverse effects. We have studied the levels of these cytokines and their correlation with leucocyte contents in platelet concentrates prepared by three different methods. Study Design and Methods: Five pools of platelet rich plasma platelet concentrates (PRP-PC and buffy-coat platelet concentrates (BC-PC each were prepared and divided into two halves. One half of the pool was leucofiltered (LF, whereas the other half was stored as such. Ten apheresis units were also included in the study. All the platelet concentrates were assessed for leucocyte load and cytokine content (IL-1β, IL-6, and TNF-α on different days of storage (0, 3, and 5 using Nageotte chamber and commercially available immunoassays respectively. Results: There was a statistically significant rise in cytokine levels (IL-1β, IL-6, and TNF-α in nonleucofiltered (NLF random donor platelet concentrates (RDPs (PRP-PC and BC-PC during storage (day 3 and 5 whereas LF RDP concentrates (PRP-PC and BC-PC and apheresis platelet concentrates (AP-PC did not show any significant rise in cytokine levels (on day 3 and 5 over the baseline values at day 0. Conclusion: This data suggests that although AP-PCs are superior to PRP-PC (NLF and BC-PC (NLF in terms of in vitro quality control parameters and cytokine generation during storage, BC-PC mode of platelet preparation followed by leucofiltration is the best method to store platelets and minimise the cytokine accumulation. This strategy is best suited for transfusion in multitransfused hematooncologic patients, who cannot afford

  15. Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Vladan P. Čokić

    2015-01-01

    Full Text Available The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34+ cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34+ cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs.

  16. Helicobacter pylori-Induced Disruption of Monolayer Permeability and Proinflammatory Cytokine Secretion in Polarized Human Gastric Epithelial Cells

    OpenAIRE

    Fiorentino, Maria; Ding, Hua; Blanchard, Thomas G.; Czinn, Steven J.; Sztein, Marcelo B.; Fasano, Alessio

    2013-01-01

    Helicobacter pylori infection of the stomach is related to the development of diverse gastric pathologies. The ability of H. pylori to compromise epithelial junctional complexes and to induce proinflammatory cytokines is believed to contribute to pathogenesis. The purpose of this study was to use an in vitro human gastric epithelial model to investigate the ability of H. pylori to affect permeability and the extent and polarity of the host inflammatory response. NCI-N87 monolayers were cocult...

  17. Tephrosia sinapou extract reduces inflammatory leukocyte recruitment in mice: effect on oxidative stress, nitric oxide and cytokine production

    OpenAIRE

    Martinez, Renata M.; Zarpelon, Ana C.; Vanessa V. M. Zimermann; Georgetti, Sandra R.; Marcela M. Baracat; Fonseca, Maria J. V.; Fabiana T. M. C. Vicentini; Isabel C. Moreira; Andrei, Cesar C.; Waldiceu A. Verri Jr; Rubia Casagrande

    2012-01-01

    Tephrosia toxicaria (Sw.) Pers., which is currently known as T. sinapou (Buc'hoz) A. Chev., Fabaceae, is a source of compounds such as flavonoids, however, few studies addressed the anti-inflammatory and antioxidant effects of T. sinapou. Therefore, we evaluated the antioxidant mechanisms of the T. sinapou ethyl acetate extract in vitro, and whether the extract affects leukocyte recruitment in four models of inflammation and the involvement of nitric oxide and cytokines in its mechanism. In v...

  18. In ovo delivery of Newcastle disease virus conjugated hybrid calcium phosphate nanoparticle and to study the cytokine profile induction

    Energy Technology Data Exchange (ETDEWEB)

    Viswanathan, Kaliyaperumal [Translational Research Platform for Veterinary Biologicals (TRPVB), Tamil Nadu Veterinary and Animal Sciences University, Chennai 600 051, Tamil Nadu (India); Rathish, P.; Gopinath, V.P.; Janice, R. [Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai 600 007 (India); Dhinakar Raj, G., E-mail: dhinakarrajg@tanuvas.org.in [Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai 600 007 (India); Translational Research Platform for Veterinary Biologicals (TRPVB), Tamil Nadu Veterinary and Animal Sciences University, Chennai 600 051, Tamil Nadu (India)

    2014-12-01

    In this report, the hybrid calcium phosphate (CaP) nanoparticles were synthesized and functionalized with Newcastle disease virus (NDV). These nanoparticles were synthesized by a combination of co-precipitation and polymerization process and functionalized with amino propyl triethoxy silane before coupling to NDV. The 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT) assay of chicken spleen cells incubated with these nanoparticles indicated that, these particles did not exert any significant cytotoxicity. The effects of hybrid CaP nanoparticles on cell cycle were assayed using a flow cytometer. The results demonstrated that the cell viability and proliferation capacity of spleen cells were not affected by hybrid CaP nanoparticles compared with their control cells. The hybrid CaP nanoparticles were characterized by scanning/transmission electron microscopy (SEM/TEM); Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD), Raman spectroscopy and energy-dispersive X-ray spectroscopy (EDX). These methods revealed that NDV was successfully conjugated on nanoparticles. The ability of the hybrid CaP nanoparticles to induce different cytokine mRNAs in the spleen cells of 18-day old embryonated chicken eggs (ECEs) was studied by quantitative real time polymerase chain reaction (qRT-PCR). NDV conjugated particles induced a high expression of Th1 cytokines such as interferon (IFN)-α, tumor necrosis factor (TNF)-α of and Th2 cytokines, interleukin (IL) 6 and IL-10. Uncoupled NDV induced only Th1 cytokines, IFN-α, INF-γ and TNF-α. The hybrid particles alone did not induce any cytokines. This confirmed that nanoparticle coupling could induce differential cytokine profiles and hence can be used as an alternate strategy to direct favorable immune responses in animals or chickens using appropriate vaccination carrier. - Highlights: • NDV conjugated hybrid CaP NP induced differential cytokine profiles in embryonated chicken eggs.

  19. In ovo delivery of Newcastle disease virus conjugated hybrid calcium phosphate nanoparticle and to study the cytokine profile induction

    International Nuclear Information System (INIS)

    In this report, the hybrid calcium phosphate (CaP) nanoparticles were synthesized and functionalized with Newcastle disease virus (NDV). These nanoparticles were synthesized by a combination of co-precipitation and polymerization process and functionalized with amino propyl triethoxy silane before coupling to NDV. The 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT) assay of chicken spleen cells incubated with these nanoparticles indicated that, these particles did not exert any significant cytotoxicity. The effects of hybrid CaP nanoparticles on cell cycle were assayed using a flow cytometer. The results demonstrated that the cell viability and proliferation capacity of spleen cells were not affected by hybrid CaP nanoparticles compared with their control cells. The hybrid CaP nanoparticles were characterized by scanning/transmission electron microscopy (SEM/TEM); Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD), Raman spectroscopy and energy-dispersive X-ray spectroscopy (EDX). These methods revealed that NDV was successfully conjugated on nanoparticles. The ability of the hybrid CaP nanoparticles to induce different cytokine mRNAs in the spleen cells of 18-day old embryonated chicken eggs (ECEs) was studied by quantitative real time polymerase chain reaction (qRT-PCR). NDV conjugated particles induced a high expression of Th1 cytokines such as interferon (IFN)-α, tumor necrosis factor (TNF)-α of and Th2 cytokines, interleukin (IL) 6 and IL-10. Uncoupled NDV induced only Th1 cytokines, IFN-α, INF-γ and TNF-α. The hybrid particles alone did not induce any cytokines. This confirmed that nanoparticle coupling could induce differential cytokine profiles and hence can be used as an alternate strategy to direct favorable immune responses in animals or chickens using appropriate vaccination carrier. - Highlights: • NDV conjugated hybrid CaP NP induced differential cytokine profiles in embryonated chicken eggs.

  20. Association of cytokine gene polymorphisms in CWP and its severity in Turkish coal workers

    Energy Technology Data Exchange (ETDEWEB)

    Ates, I.; Suzen, H.S.; Yucesoy, B.; Tekin, I.O.; Karakaya, A. [Ankara University, Ankara (Turkey)

    2008-10-15

    Cytokines appear to play a key role in some inflammatory reactions affecting the interactions among pro- and anti-inflammatory mechanisms that result in several diseases such as coal workers' pneumoconiosis (CWP). In this study, to determine the cytokine gene profiles of Turkish coal miners, we performed genotyping analysis to investigate the polymorphisms of CWP-related pro-inflammatory (TNFA, IL1A, IL1B, and IL6) and anti-inflammatory cytokines (IL-1RN and TGFB1). Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TNFA (-238) gene polymorphism principally affected CWP development and severity (OR=3.47: 95% CI, 1.12-10.77 and OR=4.30: 95% CI, 1.25-14.74, respectively) and also risk of CWP (OR=3.79: 95% CI, 1.37-10.46). The TNFA (-308) variant was associated with a risk for the CWP severity (OR = 2.84: 95% CI, 1.08-7.39). A protective effect of IL6 was found on the development (OR = 0.48: 95% CI, 0.21-0.93) and severity of CWP (OR = 0.37: 95% CI, 0.15-0.91). We suggest that TNFA (-238) variant may be a risk factor in both development and the severity, of CWP while TNFA (-308) variant seems to be important only in disease severity On the other hand, IL6 variant may have a protective effect on the development and disease severity.

  1. The Maternal Cytokine and Chemokine Profile of Naturally Conceived Gestations Is Mainly Preserved during In Vitro Fertilization and Egg Donation Pregnancies.

    Science.gov (United States)

    Martínez-Varea, Alicia; Pellicer, Begoña; Serra, Vicente; Hervás-Marín, David; Martínez-Romero, Alicia; Bellver, José; Perales-Marín, Alfredo; Pellicer, Antonio

    2015-01-01

    This prospective longitudinal study aimed at comparing maternal immune response among naturally conceived (NC; n = 25), in vitro fertilization (IVF; n = 25), and egg donation (ED; n = 25) pregnancies. The main outcome measures were, firstly, to follow up plasma levels of interleukin (IL) 1 beta, IL2, IL4, IL5, IL6, IL8, IL10, IL17, interferon gamma, tumor necrosis factor-alpha (TNFα), transforming growth factor-beta (TGFβ), regulated upon activation normal T-cell expressed and secreted (RANTES), stromal cell-derived factor 1 alpha (SDF1α), and decidual granulocyte-macrophage colony-stimulating factor (GM-CSF) during the three trimesters of pregnancy during the three trimesters of pregnancy; secondly, to evaluate if the cytokine and chemokine pattern of ED pregnant women differs from that of those with autologous oocytes and, thirdly, to assess if women with preeclampsia show different cytokine and chemokine profile throughout pregnancy versus women with uneventful pregnancies. Pregnant women in the three study groups displayed similar cytokine and chemokine pattern throughout pregnancy. The levels of all quantified cytokines and chemokines, except RANTES, TNFα, IL8, TGFβ, and SDF1α, rose in the second trimester compared with the first, and these higher values remained in the third trimester. ED pregnancies showed lower SDF1α levels in the third trimester compared with NC and IVF pregnancies. Patients who developed preeclampsia displayed higher SDF1α plasma levels in the third trimester. PMID:26346343

  2. The Maternal Cytokine and Chemokine Profile of Naturally Conceived Gestations Is Mainly Preserved during In Vitro Fertilization and Egg Donation Pregnancies

    Directory of Open Access Journals (Sweden)

    Alicia Martínez-Varea

    2015-01-01

    Full Text Available This prospective longitudinal study aimed at comparing maternal immune response among naturally conceived (NC; n=25, in vitro fertilization (IVF; n=25, and egg donation (ED; n=25 pregnancies. The main outcome measures were, firstly, to follow up plasma levels of interleukin (IL 1beta, IL2, IL4, IL5, IL6, IL8, IL10, IL17, interferon gamma, tumor necrosis factor-alpha (TNFα, transforming growth factor-beta (TGFβ, regulated upon activation normal T-cell expressed and secreted (RANTES, stromal cell-derived factor 1 alpha (SDF1α, and decidual granulocyte-macrophage colony-stimulating factor (GM-CSF during the three trimesters of pregnancy during the three trimesters of pregnancy; secondly, to evaluate if the cytokine and chemokine pattern of ED pregnant women differs from that of those with autologous oocytes and, thirdly, to assess if women with preeclampsia show different cytokine and chemokine profile throughout pregnancy versus women with uneventful pregnancies. Pregnant women in the three study groups displayed similar cytokine and chemokine pattern throughout pregnancy. The levels of all quantified cytokines and chemokines, except RANTES, TNFα, IL8, TGFβ, and SDF1α, rose in the second trimester compared with the first, and these higher values remained in the third trimester. ED pregnancies showed lower SDF1α levels in the third trimester compared with NC and IVF pregnancies. Patients who developed preeclampsia displayed higher SDF1α plasma levels in the third trimester.

  3. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis

    DEFF Research Database (Denmark)

    Kjølhede, T; Dalgas, U; Gade, A B;

    2016-01-01

    Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying...... attention to the medical treatments of the patient. At present, PwMS are routinely enrolled in immunosuppressive medication, but exercise-induced immunomodulatory effects have not been investigated under these circumstances. The objective of this study was to investigate the acute and chronic cytokines...... responses to resistance exercise training in medicated PwMS. Thirty-five people with relapsing-remitting multiple sclerosis (MS) treated with interferon (IFN)-β, were randomized to a 24-week progressive resistance training (PRT) or control group. Plasma interleukin (IL)-1β, IL-4, IL-10, IL-17F, IL-23, tumor...

  4. Changes of the cytokine profile in inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Gy(o)rgyi Müzes; Béla Molnár; Zsolt Tulassay; Ferenc Sipos

    2012-01-01

    Cytokines are indispensable signals of the mucosaassociated immune system for maintaining normal gut homeostasis.An imbalance of their profile in favour of inflammation initiation may lead to disease states,such as that is observed in inflammatory bowel diseases (IBD).Although Crohn's disease (CD) is often described as a prototype of T-helper 1-type diseases,and ulcerative colitis (UC) is traditionally viewed as a T-helper 2-mediated condition,the classic paradigm,which categorises cytokines into pro-and anti-inflammatory groups,has recently been changed.The inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological settings.None the less there are many common immunological responses in IBD that are mediated by cytokines.Although they regulate and influence the development,course and recurrence of the inflammatory process,the concrete pathogenic role of these small signaling molecules is sometimes not unambiguous in the subtypes of the disease.Our aim is to review the current information about pro-and anti-inflammatory effects of traditionally studied and recently discovered cytokines in the pathogenesis of UC and CD.The better understanding of their production and functional activity may lead to the development of new therapeutic modalities.

  5. Serum levels of melatonin and cytokines in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Naser Farhadi

    2014-04-01

    Full Text Available Cytokines are important factors of the immune system in autoimmune diseases such as multiple sclerosis (MS in which damage caused by oxidants plays a major role in the pathology. Melatonin secreted by the pineal gland has recently been considered as an antioxidant. The purpose of this study was to determine the relationship between melatonin and cytokines in patients with MS. Thirty patients with MS and 30 healthy controls were selected. Serum levels of melatonin and cytokines, including interleukin-4, interferon-γ, and tumor necrosis factor alpha (TNF-α, were detected in all participants by the enzyme-linked immunosorbent assay (ELISA method. There was a significant difference between patient and control groups in the levels of melatonin and TNF-α. Also, no significant correlation between the serum levels of melatonin and cytokines in both patient and control groups was seen. We concluded that decrease of melatonin and subsequent increase of pro-inflammatory cytokine, TNF-α, could be a factor in the inflammatory reactions in the pathologic process of MS.

  6. Correlation of restenosis after rabbit carotid endarterectomy and inflammatory cytokines

    Institute of Scientific and Technical Information of China (English)

    Jun-Jun Liang; Wei Xue; Li-Zhi Lou; Cheng Liu; Zhao-Fen Wang; Qing-Guo Li; Shao-Hua Huang

    2014-01-01

    Objective:To establish rabbit model of restenosis after carotid endarterectomy surgery, and to study tissue inflammatory cytokines(TNF-α,IL-6) involved in restenosis.Methods:A total of32 rabbits were randomly divided into two groups: model group and control group.The right common carotid artery in rabbits was damaged by carotid endar terectomy in model group.The tissues were harvested at different time points respectively, the pathological changes of the vascular wall after operation were observed at different time points.The changes of expression of tissue vascular wall inflammatory cytokines(TNF-α,IL-6) at different time points after the surgery was observed byRT-PCR, and the changes of serum inflammatory cytokines(TNF-α, IL -6) were detected byELISA.Results:The new intima appeared after7 daysof the injury and reached the peak on28 d which is uneven and significantly thicker than the control group (P<0.01).The tissue inflammatory cytokines(TNF-α,IL-6) were significantly increased after the rabbit common carotid artery injury, which was significant difference compared with normal control group(P<0.05).Conclusions:The tissue inflammatory factors significantly increase after the rabbit carotid artery injury, which suggests the mutual concurrent effects of inflammatory cytokines can result in the proliferation of vascular restenosis.

  7. The allergy adjuvant effect of particles – genetic factors influence antibody and cytokine responses

    Directory of Open Access Journals (Sweden)

    Løvik Martinus

    2005-06-01

    Full Text Available Abstract Background There is increasing epidemiological and experimental evidence for an aggravating effect of particulate air pollution on asthma and allergic symptoms and, to a lesser extent, on allergic sensitization. Genetic factors appear to influence not only the magnitude, but also the quality of the adjuvant effect of particles with respect to allergen-specific IgE (Th2-associated and IgG2a (Th1-associated responses. In the present study, we aimed to investigate how the genetic background influences the responses to the allergen and particles alone and in combination. We examined how polystyrene particles (PSP affected the IgE and IgG2a responses against the model allergen ovalbumin (OVA, after subcutaneous injection into the footpad of BALB/cA, BALB/cJ, NIH and C3H/HeN mice, Further, ex vivo IL-4, IFN-γ and IL-10 cytokine secretion by Con A-stimulated cells from the draining popliteal lymph node (PLN five days after injection of OVA and PSP separately or in combination was determined. Results PSP injected with OVA increased the levels of OVA-specific IgE antibodies in all strains examined. In contrast, the IgG2a levels were significantly increased only in NIH and C3H/HeN mice. PSP in the presence of OVA increased cell numbers and IL-4, IL-10 and IFN-γ levels in BALB/cA, NIH and C3H/HeN mice, with the exception of IFN-γ in NIH mice. However, each mouse strain had their unique pattern of response to OVA+PSP, OVA and PSP, and also their unique background cytokine response (i.e. the cytokine response in cells from mice injected with buffer only. Conclusion Genetic factors (i.e. the strain of mice influenced the susceptibility to the adjuvant effect of PSP on both secondary antibody responses and primary cellular responses in the lymph node, as well as the cellular responses to both OVA and PSP given separately. Interestingly, PSP alone induced cytokine responses in the lymph node in some of the mouse strains. Furthermore, we found that

  8. Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice.

    Directory of Open Access Journals (Sweden)

    Charles E Bane

    Full Text Available Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/- mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-α and IL-10 and delayed IL-1β and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI-/- mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI-/- animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.

  9. Vitamin B-6 restriction tends to reduce the red blood cell glutathione synthesis rate without affecting red blood cell or plasma glutathione concentrations in healthy men and women123

    OpenAIRE

    Lamers, Yvonne; O'Rourke, Bruce; Gilbert, Lesa R; Keeling, Christine; Matthews, Dwight E.; Stacpoole, Peter W.; Gregory, Jesse F.

    2009-01-01

    Background: Glutathione plays various protective roles in the human body. Vitamin B-6 as pyridoxal-5′-phosphate (PLP) is required as the coenzyme in the formation of glutathione precursors. Despite this obligatory role of PLP, previous studies from this laboratory showed that vitamin B-6 deficiency caused elevated glutathione concentrations in rat liver and human plasma.

  10. Plasma antennas

    CERN Document Server

    Anderson, Theodore

    2011-01-01

    The plasma antenna is an emerging technology that partially or fully utilizes ionized gas as the conducting medium instead of metal to create an antenna. The key advantages of plasma antennas are that they are highly reconfigurable and can be turned on and off. The disadvantage is that the plasma antennas require energy to be ionized. This unique resource provides you with a solid understanding of the efficient design and prototype development of plasma antennas, helping you to meet the challenge of reducing the power required to ionize the gas at various plasma densities. You also find thorou

  11. Kinetics of pro-inflammatory cytokines, interleukin-10, and virus neutralising antibodies during acute ephemeral fever virus infections in Brahman cattle.

    Science.gov (United States)

    Barigye, R; Melville, L F; Davis, S; Walsh, S; Hunt, N; Hunt, R; Elliot, N

    2015-12-15

    While fever and inflammation are hallmark features of bovine ephemeral fever (BEF), the cytokine networks that underlie the acute phase of the disease have not been empirically defined in cattle. This study characterised the plasma kinetics of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and IL-10 during acute BEF and elucidated on the relationship between the onset of the virus neutralizing antibody response and resolution of viraemia in natural BEF virus (BEFV) infections in cattle. Plasma from three BEFV-infected and three uninfected cattle was tested for the study cytokines by a cELISA, viraemia monitored by qRT-PCR, and virus neutralizing antibody titres determined using a standard protocol. Unlike the negative controls, plasma concentrations of IL-1β, TNF-α, IL-6, and IL-10 were consistently increased in the three virus-infected animals. Two of the infected heifers were recumbent and pyrexic on the first day of monitoring and increased cytokine production was already in progress by the time viraemia was detected in all the three infected animals. In all the virus-infected heifers, IL-1β was the most strongly expressed cytokine, IL-6 and IL-10 manifested intermediate plasma concentrations while TNF-α was the least expressed and demonstrated bi-phasic peaks three and five days after the onset of pyrexia. In two of the BEFV-infected heifers, viraemia resolved on the day of seroconversion while in the other infected animal, viral RNA was detectable up to three days after seroconversion. The present data document variable increase in plasma IL-1β, IL-6, TNF-α, and IL-10 during natural BEFV infections and the fact that upregulation of all but TNF-α precedes seroconversion. In addition to virus neutralising antibodies, it is likely that cytokine-mediated cellular mechanisms may be required for resolution of viraemia in BEF. Considering the anti-inflammatory properties of IL-10, its upregulation may potentially antagonise the fever response in BEFV

  12. High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

  13. Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicans infection

    Directory of Open Access Journals (Sweden)

    Venturini James

    2009-06-01

    Full Text Available Abstract Background In order to attain a better understanding of the interactions between opportunist fungi and their hosts, we investigated the cytokine profile associated with the inflammatory response to Candida albicans infection in mice with solid Ehrlich tumors of different degrees. Methods Groups of eight animals were inoculated intraperitoneally with 5 × 106 C. albicans 7, 14 or 21 days after tumor implantation. After 24 or 72 hours, the animals were euthanized and intraperitoneal lavage fluid was collected. Peritoneal macrophages were cultivated and the levels of IFN-γ, TNF-α, IL-12, IL-10 and IL-4 released into the supernatants were measured by ELISA. Kidney, liver and spleen samples were evaluated for fungal dissemination. Tumor-free animals and animals that had only been subjected to C. albicans infection were used as control groups. Results Our results demonstrated that the mice produced more IFN-γ and TNF-α and less IL-10, and also exhibited fungal clearance, at the beginning of tumor evolution. With the tumor progression, this picture changed: IL-10 production increased and IFN-γ and TNF-α release decreased; furthermore, there was extensive fungal dissemination. Conclusion Our results indicate that solid tumors can affect the production of macrophage cytokines and, in consequence, affect host resistance to opportunistic infections.

  14. Systemic cytokine and interferon responsiveness Patterns in HIV and HCV mono and co-infections.

    Science.gov (United States)

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael; Bordon, Jose

    2014-11-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV(+)/HCV(+)), HCV mono-infected (HIV(-)/HCV(+)), HIV mono-infected (HIV(+)/HCV(-)) female patients and HIV- and HCV-uninfected women (HIV(-)/HCV(-)) who had enrolled in the Women's Interagency HIV Study (WIHS). HIV(+)/HCV(+) women had higher plasma levels of pro-inflammatory cytokines as well as caspase-1 compared with other groups. Both HIV(+)/HCV(+) and HIV(+)/HCV(-) women had significantly higher sCD14 levels compared with other groups. Peripheral blood mononuclear cells from HCV mono-infected patients had reduced levels of phosphorylation of STAT1 compared with other groups as well as lower basal levels of expression of the IFN-stimulated genes, OAS1, ISG15, and USP18 (UBP43). Basal expression of USP18, a functional antagonist of ISG15, as well as USP18/ISG15 ratios were increased in the HIV(+)/HCV(+) group compared with HIV(-)/HCV(+) and HIV(+)/HCV(-) groups. A more pronounced systemic inflammatory profile as well as increased expression ratios of USP18 to ISG15 may contribute to the more rapid progression of liver disease in HIV(+)/HCV(+) individuals. PMID:24955730

  15. Serum Cytokines as Biomarkers of Early Trypanosoma cruzi infection by Congenital Exposure.

    Science.gov (United States)

    Volta, Bibiana J; Bustos, Patricia L; Cardoni, Rita L; De Rissio, Ana M; Laucella, Susana A; Bua, Jacqueline

    2016-06-01

    Trypanosoma cruzi, the causing agent of Chagas disease, leads to an activation of the immune system in congenitally infected infants. In this study, we measured a set of cytokines/chemokines and the levels of parasitemia by quantitative PCR in the circulation of neonates born to T. cruzi-infected mothers to evaluate the predictive value of these mediators as biomarkers of congenital transmission. We conducted a retrospective cohort study of 35 infants with congenital T. cruzi infection, of which 15 and 10 infants had been diagnosed by detection of parasites by microscopy in the first and sixth month after delivery, respectively, and the remaining 10 had been diagnosed by the presence of T. cruzi-specific Abs at 10-12 mo old. Uninfected infants born to either T. cruzi-infected or uninfected mothers were also evaluated as controls. The plasma levels of IL-17A, MCP-1, and monokine induced by IFN-γ were increased in infants congenitally infected with T. cruzi, even before they developed detectable parasitemia or seroconversion. Infants diagnosed between 6 and 12 mo old also showed increased levels of IL-6 and IL-17F at 1 mo of age. Conversely, infants who did not develop congenital T. cruzi infection had higher levels of IFN-γ than infected infants born to uninfected mothers. Monokine induced by IFN-γ, MCP-1, and IFN-γ production induced in T. cruzi-infected infants correlated with parasitemia, whereas the plasma levels of IL-17A, IL-17F, and IL-6 were less parasite load dependent. These findings support the existence of a distinct profile of cytokines and chemokines in the circulation of infants born to T. cruzi-infected mothers, which might predict congenital infection. PMID:27183607

  16. Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection

    DEFF Research Database (Denmark)

    Rønn, S G; Börjesson, A; Bruun, C; Heding, P E; Frobøse, H; Mandrup-Poulsen, T; Karlsen, A E; Rasschaert, J; Sandler, S; Billestrup, Nils

    2008-01-01

    The pro-inflammatory cytokines IL-1 and IFNgamma are critical molecules in immune-mediated beta cell destruction leading to type 1 diabetes mellitus. Suppressor of cytokine signalling (SOCS)-3 inhibits the cytokine-mediated destruction of insulinoma-1 cells. Here we investigate the effect of SOCS...

  17. The human kidney as a regulator of body cytokine homeostasis

    Directory of Open Access Journals (Sweden)

    A. Bonanni

    2011-01-01

    Full Text Available Evidence is accumulating that the human kidney is a major site for the removal of several cytokines and growth factors, which can accumulate in body pools in patients with acute and chronic kidney disease (CKD. In addition, progressive renal failure and the increase in circulating proinflammatory cytokines are associated with mortality, suggesting that altered cytokines handling by the kidney is associated with worse outcome. Also, the kidney itself may be damaged by signals arising by endothelia and peripheral tissues during the course of the metabolic syndrome, type 2 diabetes and obesity. In this paper we provide a review of kidney handling of several adipokines and myokines, with special emphasis to interleukin-6 (IL-6, leptin, resistin and transforming growth factor-beta (TGF-beta.

  18. Rheumatoid factor and its interference with cytokine measurements

    DEFF Research Database (Denmark)

    Bartels, Else Marie; Falbe Wätjen, Inger; Littrup Andersen, Eva;

    2011-01-01

    Use of cytokines as biomarkers for disease is getting more widespread. Cytokines are conveniently determined by immunoassay, but interference from present antibodies is known to cause problems. In rheumatoid arthritis (RA), interference of rheumatoid factor (RF) may be problematic. RF covers a...... group of autoantibodies from immunoglobulin subclasses and is present in 65-80% of RA patients. Partly removal of RF is possible by precipitation. This study aims at determining the effects of presence of RF in blood and synovial fluid on cytokine measurements in samples from RA patients and finding...... possible solutions for recognized problems. IL-1β, IL-4, IL-6, and IL-8 were determined with multiplex immunoassays (MIA) in samples from RA patients prior to and after polyethylene glycol (PEG 6000) precipitation. Presence of RF does interfere with MIA. PEG 6000 precipitation abolishes this RF...

  19. Rheumatoid factor and its interference with cytokine measurements

    DEFF Research Database (Denmark)

    Bartels, Else Marie; Falbe Wätjen, Inger; Littrup Andersen, Eva;

    2011-01-01

    Use of cytokines as biomarkers for disease is getting more widespread. Cytokines are conveniently determined by immunoassay, but interference from present antibodies is known to cause problems. In rheumatoid arthritis (RA), interference of rheumatoid factor (RF) may be problematic. RF covers a...... group of autoantibodies from immunoglobulin subclasses and is present in 65-80% of RA patients. Partly removal of RF is possible by precipitation. This study aims at determining the effects of presence of RF in blood and synovial fluid on cytokine measurements in samples from RA patients and finding...... possible solutions for recognized problems. IL-1ß, IL-4, IL-6, and IL-8 were determined with multiplex immunoassays (MIA) in samples from RA patients prior to and after polyethylene glycol (PEG 6000) precipitation. Presence of RF does interfere with MIA. PEG 6000 precipitation abolishes this RF...

  20. Immune deficiencies due to defects in cytokine signaling.

    Science.gov (United States)

    Kelly, John; Leonard, Warren J

    2003-09-01

    Severe combined immunodeficiency (SCID) represents a syndrome comprising the most severe forms of inherited immunodeficiencies. Defects in cytokine signaling pathways can result in impaired development of lymphoid cells and/or defective functioning of these cells, and most cases of SCID result from defective signaling through the common cytokine receptor g chain (g(c)) or associated molecules and signaling pathways. Studies of these patients and the analysis of gene-targeted mice provide insight into the underlying signaling defects in inherited immunodeficiencies. The identification of the genetic defects in humans with SCID provides the basis for future therapies for these patients. More subtle deficiencies in cytokine signaling have also been found as causes of other forms of immunodeficiency, and the knowledge learned could lead to novel approaches to antimicrobial therapy. PMID:12906775

  1. Study on serum cytokine levels in posttraumatic stress disorder patients

    Institute of Scientific and Technical Information of China (English)

    Min Guo; Tao Liu; Jun-Cheng Guo; Xiang-Ling Jiang; Feng Chen; Yun-Suo Gao

    2012-01-01

    ABSTRACT Objective:To evaluate serumIL-2, IL-4, IL-6, IL-8, IL-10 andTNF-α levels in posttraumatic stress disorder (PTSD) patients.Methods:We utilizedELISA technology to examine cytokines such asIL-2, IL-4, IL-6, IL-8, IL-10andTNF-α in serum from50 well-characterized individuals with a primaryDSM-Ⅳ PTSD diagnosis, and 50age- and gender-matched healthy controls. We conservatively employed a Mann-Whitney U testing.Results: Individuals with primaryPTSD had significantly elevated peripheral cytokine levels for all 6 different cytokines compared to age- and gender-matched healthy controls (allP<0.01).Conclusions: These findings suggest that a generalized inflammatory state may be present in individuals with PTSD.

  2. Structural basis of receptor sharing by interleukin 17 cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Ely, Lauren K.; Fischer, Suzanne; Garcia, K. Christopher; Stanford-MED

    2010-02-19

    Interleukin 17 (IL-17)-producing helper T cells (T{sub H}-17 cells), together with their effector cytokines, including members of the IL-17 family, are emerging as key mediators of chronic inflammatory and autoimmune disorders. Here we present the crystal structure of a complex of IL-17 receptor A (IL-17RA) bound to IL-17F in a 1:2 stoichiometry. The mechanism of complex formation was unique for cytokines and involved the engagement of IL-17 by two fibronectin-type domains of IL-17RA in a groove between the IL-17 homodimer interface. Binding of the first receptor to the IL-17 cytokines modulated the affinity and specificity of the second receptor-binding event, thereby promoting heterodimeric versus homodimeric complex formation. IL-17RA used a common recognition strategy to bind to several members of the IL-17 family, which allows it to potentially act as a shared receptor in multiple different signaling complexes.

  3. Cytokine profile associated with chronic and acute human schistosomiasis mansoni

    Directory of Open Access Journals (Sweden)

    Clarice Neuenschwander Lins de Morais

    2008-09-01

    Full Text Available The production and regulation of interleukin (IL IL-13, IL-4 and interferon-gamma (IFN-³ was evaluated in 43 schistosomiasis patients with different clinical forms. Whole-blood cultures cytokine production in response to soluble egg antigen (SEA, soluble worm adult preparation (SWAP, mitogens, neutralizing antibodies or recombinant IL-13 were measured by ELISA. After SWAP stimulation, chronic patients, particularly hepatointestinals, produced higher levels of IL-4 in comparison with acute patients, suggesting the presence of a type 2 cytokine profile in these patients. Following SEA and SWAP stimulation, hepatosplenic (HS patients showed increased levels of IFN-³ when compared with acute patients, indicating that HS disease in humans is associated with a type 1 cytokine response. The mechanisms of immune regulation are apparently different between the clinical stages of the disease, some of which are antigen-specific.

  4. Immunotherapeutic implications of IL-6 blockade for cytokine storm.

    Science.gov (United States)

    Tanaka, Toshio; Narazaki, Masashi; Kishimoto, Tadamitsu

    2016-07-01

    IL-6 contributes to host defense against infections and tissue injuries. However, exaggerated, excessive synthesis of IL-6 while fighting environmental stress leads to an acute severe systemic inflammatory response known as 'cytokine storm', since high levels of IL-6 can activate the coagulation pathway and vascular endothelial cells but inhibit myocardial function. Remarkable beneficial effects of IL-6 blockade therapy using a humanized anti-IL-6 receptor antibody, tocilizumab were recently observed in patients with cytokine release syndrome complicated by T-cell engaged therapy. In this review we propose the possibility that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis. PMID:27381687

  5. Influence of phthalates on cytokine production in monocytes and macrophages

    DEFF Research Database (Denmark)

    Hansen, Juliana Frohnert; Bendtzen, Klaus; Boas, Malene; Frederiksen, Hanne; Nielsen, Claus H; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla

    2015-01-01

    BACKGROUND: Phthalates are a group of endocrine disrupting chemicals suspected to influence the immune system. The aim of this systematic review is to summarise the present knowledge on the influence of phthalates on monocyte and macrophage production and secretion of cytokines, an influence which......-α secretion/production from monocytes or macrophages. A summary of cytokine measurements was not possible since few studies were comparable in study design and due to insufficient reporting of raw data for most of the included studies. CONCLUSION: Results from this review have suggested that at least one...... phthalate (di-2-ethylhexyl phthalate) has the ability to enhance tumour necrosis factor-α production/secretion from monocytes/macrophages in vitro, but also observed ex vivo. Influence of other phthalates on other cytokines has only been investigated in few studies. Thus, in vitro studies on primary human...

  6. Class I Cytokine Receptors: Structure and function in the Membrane

    DEFF Research Database (Denmark)

    Bugge, Katrine Østergaard

    of structural knowledge on their membrane-embedded transmembrane domains (TMDs), which connect the extracellular ligand binding domains to the intracellular signaling platforms. The overall aim of this thesis work was to improve our understanding of the class I cytokine receptor signaling across the membrane...... bilayer via structural characterizations of TMD representatives. To enable structural studies of these domains, an organic-extraction based strategy for efficient production of isotope-labeled TMDs with or without short intrinsically disordered regions was developed. This strategy successfully provided...... ample material of high quality for structural studies with NMR spectroscopy of several class I cytokine receptor TMDs. Furthermore, the structure of a class I cytokine receptor TMD in DHPC micelles was solved with solution-state NMR spectroscopy. Additionally, since structural studies of intact proteins...

  7. MicroRNA-Regulated Proinflammatory Cytokines in Sarcopenia

    Science.gov (United States)

    Fan, Jingjing; Kou, Xianjuan; Yang, Yi; Chen, Ning

    2016-01-01

    Sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is the major cause of frailty and falls in elders. The activation of inflammatory signal pathways due to diseases and aging is suggested to reveal the critical impact on sarcopenia. Several proinflammatory cytokines, especially interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), play crucial roles in modulation of inflammatory signaling pathway during the aging-related loss of skeletal muscle. MicroRNAs (miRNAs) have emerged as the important regulators for the mass and functional maintenance of skeletal muscle through regulating gene expression of proinflammatory cytokines. In this paper, we have systematically discussed regulatory mechanisms of miRNAs for the expression and secretion of inflammatory cytokines during sarcopenia, which will provide some novel targets and therapeutic strategies for controlling aging-related atrophy of skeletal muscle and corresponding chronic inflammatory diseases. PMID:27382188

  8. MicroRNA-Regulated Proinflammatory Cytokines in Sarcopenia

    Directory of Open Access Journals (Sweden)

    Jingjing Fan

    2016-01-01

    Full Text Available Sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is the major cause of frailty and falls in elders. The activation of inflammatory signal pathways due to diseases and aging is suggested to reveal the critical impact on sarcopenia. Several proinflammatory cytokines, especially interleukin-6 (IL-6 and tumor necrosis factor-alpha (TNF-α, play crucial roles in modulation of inflammatory signaling pathway during the aging-related loss of skeletal muscle. MicroRNAs (miRNAs have emerged as the important regulators for the mass and functional maintenance of skeletal muscle through regulating gene expression of proinflammatory cytokines. In this paper, we have systematically discussed regulatory mechanisms of miRNAs for the expression and secretion of inflammatory cytokines during sarcopenia, which will provide some novel targets and therapeutic strategies for controlling aging-related atrophy of skeletal muscle and corresponding chronic inflammatory diseases.

  9. Effect of cytokine level variations in individuals on the progression and outcome of bacterial urogenital infections--a meta-analysis.

    Science.gov (United States)

    Singer, Martin; Ouburg, Sander

    2016-03-01

    Bacterial urogenital infections such as chlamydia, gonorrhoea and syphilis are widespread inflammatory diseases, which may be accompanied by severe complications. These complications can range from basic inflammation to tubal pathology, infertility and neurological dysfunction, though infections go unnoticed in the majority of cases. Cytokines in the host play a vital role in both the initial and long-term immune response and inflammation. However, levels of cytokine expression vary between individuals. A meta-analysis was performed to evaluate the effect of cytokine expression differences on severity of infections with these pathogens. Studies comparing expression of cytokines in humans with inflammation or inflammation-based complications were identified using NCBI, Google Scholar and Cochrane databases. Only studies into human cytokine expressions were included, and three articles per subject were required to be suitably analysed during meta-analysis. A total of 52 articles were included for meta-analysis. It was shown that differences in IL-1, IL-6, IL-8, IL-10, TNFα and IFNγ affect the clinical outcome of Chlamydia trachomatis infection significantly. Similarly, IL-1 and IL-8 expression during Neisseria gonorrhoeae infection significantly affects the outcome of the disease. For Treponema pallidum infection, it was shown that IFNγ variation in hosts could be linked to severity of disease. However, a lack of studies to use in the meta-analysis and fluctuation in the resulting data depending on the adjustments makes adequate evaluation difficult. PMID:26733496

  10. How does real affect affect affect recognition in speech?

    NARCIS (Netherlands)

    Truong, Khiet Phuong

    2009-01-01

    The aim of the research described in this thesis was to develop speech-based affect recognition systems that can deal with spontaneous (‘real’) affect instead of acted affect. Several affect recognition experiments with spontaneous affective speech data were carried out to investigate what combinati

  11. Dysregulation of suppressor of cytokine signaling 3 in keratinocytes causes skin inflammation mediated by interleukin-20 receptor-related cytokines.

    Directory of Open Access Journals (Sweden)

    Ayako Uto-Konomi

    Full Text Available Homeostatic regulation of epidermal keratinocytes is controlled by the local cytokine milieu. However, a role for suppressor of cytokine signaling (SOCS, a negative feedback regulator of cytokine networks, in skin homeostasis remains unclear. Keratinocyte specific deletion of Socs3 (Socs3 cKO caused severe skin inflammation with hyper-production of IgE, epidermal hyperplasia, and S100A8/9 expression, although Socs1 deletion caused no inflammation. The inflamed skin showed constitutive STAT3 activation and up-regulation of IL-6 and IL-20 receptor (IL-20R related cytokines, IL-19, IL-20 and IL-24. Disease development was rescued by deletion of the Il6 gene, but not by the deletion of Il23, Il4r, or Rag1 genes. The expression of IL-6 in Socs3 cKO keratinocytes increased expression of IL-20R-related cytokines that further facilitated STAT3 hyperactivation, epidermal hyperplasia and neutrophilia. These results demonstrate that skin homeostasis is strictly regulated by the IL-6-STAT3-SOCS3 axis. Moreover, the SOCS3-mediated negative feedback loop in keratinocytes has a critical mechanistic role in the prevention of skin inflammation caused by hyperactivation of STAT3.

  12. T-2 Toxin Regulated Ganoderma lucidum Induced Cytokine Release

    Directory of Open Access Journals (Sweden)

    Kazem Ahmadi

    2008-01-01

    Full Text Available The water-soluble extract of Ganoderma lucidum (Reishi has been used as immunomodulator to stimulate spleen cells proliferation and cytokine expression. It has also been shown that at some level of exposure, T-2 toxin typically act as immunosuppressive agent and can increase disease susceptibility. The aim of this study was to investigate the effect of T-2 toxin on cytokine production by Ganoderma lucidum (G. lucidum treated-cells. Mice peritoneal macrophages and lymphoid T cells were prepared by usual manner and plated out at 1106 or 1104 cell/well respectively in RPMI 1640 supplemented with 10% FCS, 50 µg streptomycin and 50U penicillin. Cells were incubated with different concentrations of G. lucidum in the presence or absence of 1 ng mL-­1 T-2 toxin at 37°C and 5% CO2 for 48 h. Cell free medium was removed and used for cytokine assay by ELISA method. The results showed that T-2 toxin in the absence of G.lucidum enhanced IL-2, IFN-γ release compared with control group, but it reduced the production of other cytokines. G. lucidum enhanced the production of IL-1β TNF-α, IL-12, IL-2 and IFN-γ compared with control group, but reduced IL-4 and IL-10 release. T-2 toxin, up regulated the enhancement effect of G. lucidum on IFN-γ, IL-2 and TNF-α, but it down regulated its effect on the production of other cytokines. In conclution our results indicate that T-2 toxin at 1 ng mL-1 may augment the immunomodulating effects of G. lucidum on cytokine release.

  13. Early-response cytokine expression in adult middle ear effusions.

    Science.gov (United States)

    Ondrey, F G; Juhn, S K; Adams, G L

    1998-10-01

    Various cytokines are presently known to be associated with the regulation of inflammatory responses. In pediatric otitis media, cytokines that correlate with various degrees of inflammation are present in middle ear effusions as inflammatory mediators. The present study was undertaken to examine the potential role of the early-response cytokines, interleukin-1beta and tumor necrosis factor-alpha, in adult otitis media. Fifty-nine adults with otitis media underwent tympanocentesis, and the effusion specimens were analyzed for the presence of both cytokines by enzyme-linked immunosorbent assay methods. Eighty-eight percent of the effusions were serous in nature. Sixty-seven percent of the patients had a known history of head and neck malignancy and radiation to the temporal bone. Twelve percent of the effusions were positive for interleukin-1beta expression, compared with 85% of effusions in children with otitis media. Eight percent of the effusions contained tumor necrosis factor-alpha, compared with 85% of those collected in pediatric otitis media. All of the specimens that contained tumor necrosis factor-alpha also contained interleukin-1beta. In the present study, there was no correlation with head and neck malignancy/radiation or the clinical degree of inflammation with the presence of either cytokine. We conclude that adult otitis media is associated with lower expression of an acute inflammatory response, as judged by the levels of interleukin-1beta and tumor necrosis factor-alpha in the effusions. Additionally, adult otitis probably represents a less severe and more chronic inflammatory state in comparison with pediatric otitis media. Further analysis of inflammatory mediators in adult otitis media is necessary to evaluate the contribution of cytokines in relation to various etiologic factors. PMID:9781987

  14. IL-1 beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

    DEFF Research Database (Denmark)

    Jacobsen, M.L.B.; Ronn, S.G.; Bruun, C.; Larsen, C.M.; Eizirik, D.L.; Mandrup-Poulsen, T.; Billestrup, N.

    2009-01-01

    -induced Fas and chemokine expression in beta cells. Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

  15. IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

    DEFF Research Database (Denmark)

    Jacobsen, M L B; Rønn, S G; Bruun, C; Larsen, C M; Eizirik, D L; Mandrup-Poulsen, T; Billestrup, N

    2008-01-01

    -induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

  16. Insights into pathogenesis and treatment of cytokines in cardiomyopathy.

    Science.gov (United States)

    Vadlamani, L; Abraham, W T

    2000-03-01

    Our understanding of the pathophysiology of chronic heart failure is rapidly expanding. recent investigations suggest a role for various proinflammatory and vasoconstrictive cytokines in the development and progression of the disease. In particular, tumor necrosis factor-alpha, interlukin-6, and endothelin have all been implicated in heart failure desease progression. These cytokines appear to be activated in response to a remodeling, induction of programmed cell death, neurohormonal activation, and hemodynamics, these agents cause a variety of deleterious effects in the setting of ventricular dysfunction. Investigational inhibitors and antagonists of these substances show promise for the future treatment of heart failure. PMID:10980882

  17. Cytokines of the LIF/CNTF family and metabolism.

    Science.gov (United States)

    Pasquin, Sarah; Sharma, Mukut; Gauchat, Jean-François

    2016-06-01

    The incidence of obesity is increasing worldwide. Obesity is accompanied by a chronic inflammatory state that increases the risk of metabolic diseases such as insulin-resistance and type 2 diabetes. Over the past two decades, interest in immunomodulatory cytokines as potential mediators and/or targets for treatment or prevention of obesity and metabolic syndrome has increased. In this review, we summarize studies that revealed the effects of LIF family cytokines on adipose tissue, energy expenditure and food intake, highlighting the importance of gp130/LIFRβ signaling in obesity and obesity-related metabolic diseases. PMID:26817395

  18. Old drug, new tricks: haloperidol inhibits secretion of proinflammatory cytokines

    OpenAIRE

    Moots, R.; Al-Saffar, Z; Hutchinson, D.; Golding, S; Young, S.; Bacon, P; McLaughlin, P

    1999-01-01

    OBJECTIVES—It was noted that treatment of a patient with acute mania by haloperidol was associated with marked improvement in activity of rheumatoid arthritis. The objective of this study was to examine the effects of haloperidol on inflammatory cytokine release in vitro, as a potential mechanism to explain the in vivo anti-inflammatory effects of haloperidol.
METHODS—The effect of haloperidol on the production of inflammatory cytokines interleukin 1β (IL1β) and tumour necrosis factor α (TNFα...

  19. PORCINE CYTOKINE RESPONSES TO PAMP-STRUCTURES IN VITRO

    DEFF Research Database (Denmark)

    Sørensen, Nanna Skall; Skovgaard, Kerstin; Vorsholt, Henriette; Heegaard, Peter M. H.

    monitored at mRNA-level only. However, mRNA levels do not always correlate with corresponding protein levels, and translational regulation is abundant, e.g. exerted by microRNAs through inhibition of mRNA-translation. Here, the kinetics and magnitude of induction of cytokines (IFN-α, IL-12 p40, IL-1β, TNF...... the protein response in most cases being slower than the mRNA response, as expected. Different PAMPs induced different cytokines with varying kinetics of induction. In some cases qPCR appeared more sensitive than ELISA, but to what degree this could be explained by translational inhibition or by...

  20. Serum cytokine levels in Kleine-Levin syndrome

    DEFF Research Database (Denmark)

    Kornum, Birgitte Rahbek; Rico, Thomas; Lin, Ling;

    2015-01-01

    unknown. The objective of this study was to determine serum cytokine levels in patients with KLS during and between episodes. PATIENTS/METHODS: Fifty-two typical KLS patients were included in the study of whom 17 patients donated blood samples both during and between episodes. Blood samples were collected...... patients and age- and gender matched healthy controls (n = 8/group) whose blood samples were all collected and processed at the same day; asymptomatic KLS patients had significantly higher levels of serum sVCAM1 cytokine compared to healthy controls. CONCLUSION: These data suggest that KLS episodes are not...