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Sample records for factor alpha interleukin-6

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

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    N. Konuk

    2007-01-01

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

  2. Tumor necrosis factor-alpha and interleukin-6 in early-onset neonatal sepsis

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    Prambudi Rukmono

    2016-05-01

    Full Text Available Background Neonatal sepsis remains a major cause of mortality and morbidity in newborns. Early-onset neonatal sepsis occurs in infants under the age of 72 hours, while late-onset neonatal sepsis occurs in infants over the age of 72 hours and may be due to nosocomial infection. Diagnosing neonatal sepsis is a challenge, as its clinical symptoms are not clear. Corroborating tests include routine blood, C-reactive protein (CRP, serology, tumor necrosis factor-alpha (TNF-α, and interleukin-6 (IL-6 examinations.Objective To compare the TNF-α and IL-6 levels in patients with proven and unproven early-onset neonatal sepsis (EONSMethods This case-control study was done in the Perinatology Unit, Abdul Moeloek Hospital, Lampung. Subjects were under the age of 72 hours with risk factors and clinical symptoms of sepsis. They underwent routine blood tests and blood cultures. Infants with positive cultures were considered to have proven sepsis (26 subjects and infants with negative blood cultures were considered to have unproven sepsis (26 subjects. All subjects underwent serological examinations of TNF-α and IL-6.Results There were no differences in the basic characteristics of subjects between the two groups. Levels of TNF-α in the sepsis group were significantly higher than in the unproven group [(28.30 vs. 10.96 pg/mL, respectively (P=0.001]. Furthermore, Il-6 was significantly higher in the proven sepsis group than in the unproven sepsis group [(28.3 vs. 9.69 pg/mL, respectively (P=0.006].Conclusion Levels of TNF-alpha and IL-6 are significantly higher in infants with proven than unproven early-onset neonatal sepsis.

  3. DIAGNOSTIC-VALUE OF PLASMA-LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) AND INTERLEUKIN-6 (IL-6) IN NEWBORNS WITH SEPSIS

    NARCIS (Netherlands)

    DEBONT, ESJM; MARTENS, A; VANRAAN, J; SAMSON, G; FETTER, WPF; OKKEN, A; DELEIJ, LHFM; KIMPEN, J

    The aim of this study was to examine if TNF alpha and IL-6 plasma levels could be of value in diagnosing neonatal sepsis. Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) plasma levels were determined in 15 newborn infants with confirmed sepsis (group I), 18 with suspected sepsis

  4. Apoptotic neutrophils containing Staphylococcus epidermidis stimulate macrophages to release the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6.

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    Wilsson, Asa; Lind, Sara; Ohman, Lena; Nilsdotter-Augustinsson, Asa; Lundqvist-Setterud, Helen

    2008-06-01

    Staphylococcus epidermidis infections are usually nosocomial and involve colonization of biomaterials. The immune defense system cannot efficiently control the bacteria during these infections, which often results in protracted chronic inflammation, in which a key event is disturbed removal of neutrophils by tissue macrophages. While ingesting uninfected apoptotic neutrophils, macrophages release anti-inflammatory cytokines that lead to resolution of inflammation. In clinical studies, we have previously found elevated levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in synovial fluid from prostheses infected with coagulase negative staphylococci. We show that macrophages phagocytosing apoptotic neutrophils containing S. epidermidis released TNF-alpha and interleukin-6, whereas macrophages phagocytosing spontaneously apoptotic neutrophils did not. This difference was not due to dissimilar phagocytic capacities, because macrophages ingested both types of neutrophils to the same extent. The activation was induced mainly by the apoptotic neutrophils themselves, not by the few remaining extracellular bacteria. Macrophages were not activated by apoptotic neutrophils that contained paraformaldehyde-killed S. epidermidis. Proinflammatory reactions induced by clearance of apoptotic neutrophils containing S. epidermidis might represent an important mechanism to combat the infective agent. This activation of macrophages may contribute to the development of chronic inflammation instead of inflammation resolution.

  5. Trimestral variations of C-reactive protein, interleukin-6 and tumour necrosis factor-alpha are similarly associated with survival in haemodialysis patients

    NARCIS (Netherlands)

    C.L. Meuwese; S. Snaedal; N. Halbesma; P. Stenvinkel; F.W. Dekker; A.R. Qureshi; P. Barany; O. Heimburger; B. Lindholm; R.T. Krediet; E.W. Boeschoten; J.J. Carrero

    2011-01-01

    Background. The impact of intra-individual changes of inflammatory markers [other than C-reactive protein (CRP)] on mortality in haemodialysis (HD) patients is unknown. We therefore studied survival in relation to trimestral variations of CRP, interleukin-6 (IL-6) and tumour necrosis factor-alpha (T

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

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    Kolsum, Umme; Roy, Kay; Starkey, Cerys

    2009-01-01

    BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...... (CRP) over one year and examined the relationships between these systemic markers in COPD. METHODS: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

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

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    Kolsum, Umme; Roy, Kay; Starkey, Cerys

    2009-01-01

    BACKGROUND: Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein......(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. RESULTS: There was moderate repeatability with a very high degree of statistical significance (p...... (CRP) over one year and examined the relationships between these systemic markers in COPD. METHODS: Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R...

  8. Evaluation of ferritin, interleukin-6, interleukin-8 and tumor necrosis factor alpha in the differentiation of exudates and transudates in pleural effusions.

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    Alexandrakis, M G; Coulocheri, S A; Bouros, D; Eliopoulos, G D

    1999-01-01

    In an attempt to define diagnostic criteria for the differentiation of pleural exudates from transudates, we measured ferritin (FER), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and blood serum in 84 consecutive patients with pleural effusions of various etiologies. Concentrations of FER, IL-8 and TNF-alpha were significantly higher in serum and pleural effusion in patients with exudates than in patients with transudates. Serum concentrations of IL-6 were not significantly increased in pleural exudate patients (9.78 +/- 17.12 fmol/L) compared to transudate patients (4.05 +/- 2.33 fmol/L), while significant differences were found between pleural exudates and transudates (p exudates from transudates.

  9. Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

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    Bruunsgaard, H.; Ladelund, S.; Pedersen, Agnes Nadelmann

    2003-01-01

    Ageing is associated with low-grade inflammation and markers such as IL-6 possess prognostic value. Tumour necrosis-alpha (TNF-alpha ) initiates the inflammatory cascade and has been linked to several age-associated disorders. It remains, however, unknown if TNF-alpha is associated with mortality...... in old populations. The aim of the present study was to investigate if serum levels of TNF-alpha were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF......% of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate...

  10. TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-1-BETA, AND INTERLEUKIN-6 PLASMA-LEVELS IN NEONATAL SEPSIS

    NARCIS (Netherlands)

    DEBONT, ESJM; MARTENS, A; VANRAAN, J; SAMSON, G; FETTER, WPF; OKKEN, A; DELEIJ, LHFM

    Tumor necrosis factor-alpha, IL-1beta, and IL-6 are thought to be involved in the pathogenesis of sepsis with gram-negative bacteria. We studied these cytokines during neonatal sepsis with mainly gram-positive bacteria. Ten newborns with clinical sepsis and 22 healthy controls were enrolled in the

  11. Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

    DEFF Research Database (Denmark)

    Bruunsgaard, H; Ladelund, S; Pedersen, A N

    2003-01-01

    in old populations. The aim of the present study was to investigate if serum levels of TNF-alpha were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF......% of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate...... that at least in old populations chronic elevated levels of TNF-alpha and IL-6 have different biological functions that trigger age-associated pathology and cause mortality....

  12. Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

    DEFF Research Database (Denmark)

    Bruunsgaard, H; Ladelund, S; Pedersen, A N

    2003-01-01

    in old populations. The aim of the present study was to investigate if serum levels of TNF-alpha were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF......% of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate...

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

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    Ni Made Laksmi Utari

    2015-01-01

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

  14. Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people

    DEFF Research Database (Denmark)

    Bruunsgaard, H; Ladelund, S; Pedersen, A N

    2003-01-01

    in old populations. The aim of the present study was to investigate if serum levels of TNF-alpha were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF...... that at least in old populations chronic elevated levels of TNF-alpha and IL-6 have different biological functions that trigger age-associated pathology and cause mortality....

  15. The Effect of a Prophylactic Dose of Ibuprofen on Plasma Level of Interleukin 1, Interleukin 6 and Tumor Necrosis Factor-Alpha in a 1500 m Running Practice

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    Gholamreza Sepehri

    2011-01-01

    Full Text Available Problem statement: there are controversies about the effects of anti-inflammatory drugs on exercised induced changes on plasma cytokines in untrained male athletes, so the primary purpose of this study was to measure the influence of a prophylactic dose of ibuprofen use on plasma cytokines during a 1500 m running race. Approach: Subjects were 10 untrained male Medical University students who consumed 400 mg ibuprofen two hours before the 1500 m running practice and 10 controls that competed in the race but avoided ibuprofen and all other medications. Blood samples were collected before, 1h and 24 h following the 1500 m exercise bout to measure plasma concentrations of interleukin-1 beta (IL-1β , interleukin-6(IL-6 and tumor necrosis factor alpha (TNF- α . Results: There were not any significant differences between plasma concentration of IL-1β, IL-6 and TNF- α during the study period. Also the data showed that there were not any significant differences between plasma level of IL-1β, IL-6 and TNF- α in ibuprofen and control group during the study period. Conclusions/Recommendation: Our result showed that a prophylactic dose of ibuprofen did not affect acute inflammatory cytokines levels (IL-1β, IL-6 and TNF- α in untrained healthy young males. So the etiology of the muscle soreness in athletes actively participating in sport races seems to be independent of inflammatory processes.

  16. Effects of a 1-year supplementation with cholecalciferol on interleukin-6, tumor necrosis factor-alpha and insulin resistance in overweight and obese subjects.

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    Beilfuss, Julia; Berg, Vivian; Sneve, Monica; Jorde, Rolf; Kamycheva, Elena

    2012-12-01

    Insufficient vitamin D status has been linked to autoimmune diseases, cancer and metabolic disorders, like obesity and insulin resistance. In vitro and animal studies suggest that vitamin D may play a crucial role in immune activation and inflammation. The relation between vitamin D and pro-inflammatory cytokines is not completely established. Furthermore, it is not known if the effect of vitamin D on entities of metabolic syndrome is mediated through its effect on cytokines or other biomarkers. The objectives of this study were to investigate if there is a relationship between vitamin D status and such pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and high sensitive C-reactive protein (hs-CRP) in patients with overweigh and obesity. We also proposed that the intervention with high dose of cholecalciferol may have effect on the cytokine levels and result in corresponding changes in the measures of insulin resistance (HOMA-IR and QUICKI). Serum levels of IL-6, TNF-α and hs-CRP were measured in 332 overweight and obese subjects who completed a 1-year randomised intervention with either 40,000 IU vitamin D (cholecalciferol) per week or 20,000 IU vitamin D per week, or placebo. We found significant associations between IL-6, TNF-α, vitamin D and insulin resistance indices at baseline. One year intervention with vitamin D decreased serum IL-6 levels; however hs-CRP levels were significantly increased. Neither measures of insulin resistance, nor TNF-α were influenced by a 1-year vitamin D supplementation.

  17. Promoter variants in interleukin-6 and tumor necrosis factor alpha and risk of coronary artery disease in a population from Western India

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    Aparna A Bhanushali

    2013-01-01

    Full Text Available Introduction: A central component of the atherosclerotic process is inflammation. Single nucleotide polymorphisms (SNPs present in the promoter region of various cytokines can lead to altered levels of the transcript and a state of low-grade inflammation exacerbating the risk of coronary artery disease (CAD. The present work tries to understand the role of permissive promoter variants in the interleukin-6 gene (IL-6-174G/C and the tumor necrosis factor alpha (TNFα-308G/A in the causation of CAD and also dyslipidemia. Materials and Methods: Genotyping was conducted on 100 cases of CAD and 150 controls by the allele termination assay SNaPshot. Biochemical parameters were determined by routine enzymatic endpoint methods. The results were analyzed by appropriate statistical methods. Results: No differences in the minor allele frequency IL-6-174G/C SNP were seen between cases and controls (0.13 vs. 0.12. The differences in the allele frequency of TNFα-308A between cases (6% and controls (2% have led to an odds ratio, 3.370; 95% confidence interval, 1.039-11.543; P=0.033 in the univariate analysis. In the final logistic regression analysis, however none of the variants were associated with an increased risk of CAD. Conclusions: In summary, no association of the permissive promoter variants in the IL-6 gene and the TNFα gene were seen with an increased CAD risk. These and other studies highlight the importance of doing population specific studies.

  18. Concentrations of triiodothyronine (T3), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in milk from healthy and naturally infected quarters of cows.

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    Slebodziński, A B; Malinowski, E; Lipczak, W

    2002-02-01

    The effect of naturally acquired bacterial infection of the bovine udder on the activity of 5'-thyroxine monodeiodinase (5'-MD), and on the concentrations of the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha in milk, from healthy (control) and inflamed quarters, was determined. The diagnostic procedure included history and clinical examination of the udder, macroscopic evaluation of secretions, the Californian Mastitis Test, determination of somatic cell counts and bacteriological examination of milk. It has been found that the milk triiodothyronine (T3) content and the 5'-MD activity from inflamed quarters were decreased when compared with controls. The decrease in the milk T3 from subclinical mastitic quarters was manifested when somatic cell counts were > 10(6) ml(-1). TNF-alpha was on average 2-fold higher in infected milk, and the concentration of IL-6 was unchanged. These results suggest that the decreased T3 content in mammary secretions during naturally occurring mastitis is associated with the severity of inflammation, increased TNF-alpha concentration and impaired enzymatic activity of 5'-MD.

  19. Effect of aerobic training on plasma levels and subcutaneous abdominal adipose tissue gene expression of adiponectin, leptin, interleukin 6, and tumor necrosis factor alpha in obese women.

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    Polak, Jan; Klimcakova, Eva; Moro, Cedric; Viguerie, Nathalie; Berlan, Michel; Hejnova, Jindriska; Richterova, Blanka; Kraus, Ivan; Langin, Dominique; Stich, Vladimir

    2006-10-01

    Adipocytokines secreted by adipose tissue are suggested to play a role in the development of obesity-related complications. Regular aerobic exercise has been shown to reduce the risk of metabolic complications in obese subjects. The aim of this study was to investigate the effect of aerobic training on gene expression in subcutaneous abdominal adipose tissue (SCAAT) and on plasma levels of several adipocytokines in obese women. Twenty-five obese sedentary premenopausal women (body mass index, 32.18 +/- 3.17 kg/m(2)) underwent a 12-week aerobic exercise program, with a frequency of 5 d/wk and intensity corresponding to 50% of individual maximal oxygen consumption (V(.-)(O(2)max)) consisting of 2 sessions per week of supervised aerobic exercise and 3 sessions per week of home-based exercise on a bicycle ergometer. Before and after the aerobic training, (V(.-)(O(2)max)) and body composition were measured and plasma and SCAAT biopsy samples (in a subgroup of 8 subjects) were obtained for determination of plasma and messenger RNA levels of adipocytokines (leptin, adiponectin, interleukin 6, tumor necrosis factor alpha). The aerobic training resulted in an increase of subjects' V o(2)max by 12.8% (24.6 +/- 3.9 vs 27.7 +/- 4.8 mL x min(-1) x kg(-1), P < .05). Body weight and fat mass were reduced by 5.9% (88.5 +/- 8.2 vs 83.3 +/- 7.7 kg, P < .001) and 6.4% (38.8 +/- 4.2% vs 36.3 +/- 4.6%, P < .001), respectively, and the revised QUantitative Insulin sensitivity ChecK Index (QUICKI) increased (0.43 +/- 0.06 vs 0.48 +/- 0.06, P < .05) during the aerobic training. No aerobic training-induced changes in messenger RNA levels of the investigated genes in SCAAT were observed. A decrease of plasma leptin (24.3 +/- 8.7 vs 18.1 +/- 8.3 ng/mL, P < .05) was detected, whereas plasma levels of other cytokines remained unchanged. In moderately obese females, 3 months' aerobic training did not promote changes in the adipose tissue gene expression or plasma levels of the adipocytokines

  20. Inhibition of tumor necrosis factor-alpha-induced interleukin-6 expression by telmisartan through cross-talk of peroxisome proliferator-activated receptor-gamma with nuclear factor kappaB and CCAAT/enhancer-binding protein-beta.

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    Tian, Qingping; Miyazaki, Ryohei; Ichiki, Toshihiro; Imayama, Ikuyo; Inanaga, Keita; Ohtsubo, Hideki; Yano, Kotaro; Takeda, Kotaro; Sunagawa, Kenji

    2009-05-01

    Telmisartan, an angiotensin II type 1 receptor antagonist, was reported to be a partial agonist of peroxisome proliferator-activated receptor-gamma. Although peroxisome proliferator-activated receptor-gamma activators have been shown to have an anti-inflammatory effect, such as inhibition of cytokine production, it has not been determined whether telmisartan has such effects. We examined whether telmisartan inhibits expression of interleukin-6 (IL-6), a proinflammatory cytokine, in vascular smooth muscle cells. Telmisartan, but not valsartan, attenuated IL-6 mRNA expression induced by tumor necrosis factor-alpha (TNF-alpha). Telmisartan decreased TNF-alpha-induced IL-6 mRNA and protein expression in a dose-dependent manner. Because suppression of IL-6 mRNA expression was prevented by pretreatment with GW9662, a specific peroxisome proliferator-activated receptor-gamma antagonist, peroxisome proliferator-activated receptor-gamma may be involved in the process. Telmisartan suppressed IL-6 gene promoter activity induced by TNF-alpha. Deletion analysis suggested that the DNA segment between -150 bp and -27 bp of the IL-6 gene promoter that contains nuclear factor kappaB and CCAAT/enhancer-binding protein-beta sites was responsible for telmisartan suppression. Telmisartan attenuated TNF-alpha-induced nuclear factor kappaB- and CCAAT/enhancer-binding protein-beta-dependent gene transcription and DNA binding. Telmisartan also attenuated serum IL-6 level in TNF-alpha-infused mice and IL-6 production from rat aorta stimulated with TNF-alpha ex vivo. These data suggest that telmisartan may attenuate inflammatory process induced by TNF-alpha in addition to the blockade of angiotensin II type 1 receptor. Because both TNF-alpha and angiotensin II play important roles in atherogenesis through enhancement of vascular inflammation, telmisartan may be beneficial for treatment of not only hypertension but also vascular inflammatory change.

  1. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNF alpha inhibitors

    DEFF Research Database (Denmark)

    Pedersen, S.J.; Hetland, M.L.; Sørensen, Inge Juul;

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated...... with tumor necrosis factor-alpha (TNF alpha) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n = 32, and psoriatic arthritis, n = 17) initiating TNF alpha inhibitor therapy (infliximab, n = 38......Euro parts per thousand 0.001), whereas total aggrecan was lower (662 mu g/l (223-2,219) vs. 816 (399-2,190),p a parts per thousand currency signaEuro parts per thousand 0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p a parts per thousand currency signa...

  2. Effect of topical application of melatonin on serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in patients with type 1 or type 2 diabetes and periodontal disease.

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    Cutando, Antonio; Montero, Javier; Gómez-de Diego, Rafael; Ferrera, María-José; Lopez-Valverde, Antonio

    2015-12-01

    The present clinical trial study was designed to assess the effect of topical application of melatonin on serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) in patients with diabetes and periodontal disease in comparison with healthy controls. Serum levels of TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay and CRP by nephelometry by using the proper commercial kits in 30 patients with diabetes and periodontal disease, and also in a control group of 30 healthy subjects. Periodontograms were performed using the Florida Probe®. Patients with diabetes were treated with a topical application of melatonin (1% orabase cream formula) once daily for 20 days. Healthy subjects were treated with a placebo orabase cream. Patients with diabetes and periodontal disease had significantly higher mean levels of serum TNF-α, IL-6 and CRP than healthy subjects (P diabetes and periodontal disease resulted in a significant decrease in CRP and IL-6 serum levels as well as an improvement in the gingival index and pocket depth. Patients with periodontal disease had significantly higher serum CRP, IL-6 and TNF-α values by comparison with healthy subjects. We conclude that melatonin can modulate the inflammatory action of these molecules in periodontal patients. Melatonin, periodontal disease, diabetes mellitus, interleukin-6, tumor necrosis factor-alpha, C-reactive protein, inflammatory markers.

  3. Lactate induces tumour necrosis factor-alpha, interleukin-6 and interleukin-1beta release in microglial- and astroglial-enriched primary cultures.

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    Andersson, Anna K; Rönnbäck, Lars; Hansson, Elisabeth

    2005-06-01

    Hyperammonaemia has deleterious effects on the CNS in patients with liver dysfunction. Cellular mechanisms underlying the effects of hyperammonaemia are largely unknown, although astrocytes have been the main target of interest. This study investigated how treatment with NH4Cl and lactate, which increase in the brain as a consequence of hyperammonaemia, affects cells in primary rat cultures enriched in either astrocytes or microglia. Morphological changes were studied over time using light microscopy. Release of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-1beta was measured using ELISA. NH4Cl was found to induce vacuole formation in both culture systems. Lactate treatment altered astrocytic appearance, resulting in increased space between individual cells. Microglia adopted a round morphology with either NH4Cl or lactate treatment. Lactate, but not NH4Cl, induced release of TNF-alpha and IL-6 in both astroglial- and microglial-enriched cultures, while IL-1beta was released only in microglial cultures. Cytokine release was higher in the microglial- than in the astroglial-enriched cultures. Additionally, the astroglial-enriched cultures containing approximately 10% microglial cells released more cytokines than cultures containing about 5% microglial cells. Taken together, our data suggest that most TNF-alpha, IL-6 and IL-1beta release comes from microglia. Thus, microglia could play an important role in the pathological process of hyperammonaemia.

  4. The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.

    LENUS (Irish Health Repository)

    Harmon, D

    2012-02-03

    Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol\\/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg\\/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.

  5. Increased tumor necrosis factor alpha and interleukin-6 serum levels and their correlation with laboratory parameters in patients with imported malaria

    Directory of Open Access Journals (Sweden)

    Poluga Jasmina

    2012-01-01

    Full Text Available In malaria, blood concentrations of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α and interleukin (IL-6, are increased. In a study which included 34 patients, TNF-α and IL-6 were examined in two phases, immediately after the admission of patients, and at the end of antimalarial therapy, when the parasitemia was negative. The results show a significant increase of TNF-α and IL-6 in the first phase, before the effects of antimalarial therapy. A very strong correlation between TNF-α and IL-6 is also confirmed, which suggests their coordinated production. Increased TNF-α values were correlated with an older age, the level of parasitemia, the number of platelets and leukocytes, elevated values of procalcitonin, D-dimer and lactate dehydrogenasе, and lower values of serum iron and antithrombin. Increased values of IL-6 were correlated with the level of parasitemia, the number of platelets and leukocytes, and elevated values of D-dimer and lactates.

  6. 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.

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

    Science.gov (United States)

    Hernández-Jiménez, Claudia; García-Torrentera, Rogelio; Olmos-Zúñiga, J Raúl; Jasso-Victoria, Rogelio; Gaxiola-Gaxiola, Miguel O; 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 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.

  8. Survival of malnourished head and neck cancer patients can be predicted by human leukocyte antigen-DR expression and interleukin-6/tumor necrosis factor-alpha response of the monocyte.

    Science.gov (United States)

    van Bokhorst-de van der Schuer; von Blomberg-van der Flier, B M; Kuik, D J; Scholten, P E; Siroen, M P; Snow, G B; Quak, J J; van Leeuwen, P A

    2000-01-01

    Patients with advanced stages of head and neck cancer are often characterized by malnutrition and by an impaired immune system. Because some of the suppressed immune parameters were shown to be of prognostic importance in trauma and sepsis, we investigated whether these would also correlate with survival in head and neck cancer. Severely malnourished head and neck cancer patients undergoing ablative and reconstructive surgery were followed prospectively and their perioperative immune parameters were related to long-term survival. Forty-nine patients with a preoperative weight loss of more than 10% were followed up for a period of at least 16 months after surgery. Analyses of variance revealed that preoperative human leukocyte antigen-DR (HLA-DR) expression on monocytes and endotoxin-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were different between patients who survived and patients who died. Proportional hazards identified a weight loss of more than 12%, the presence of coexistent disease, and an HLA-DR expression on monocytes below the cutoff points (mean fluorescence index < 15, peak channel index < 9) to be of significant influence on survival. In addition to known prognostic parameters such as tumor stage, coexistent disease, and weight loss, the immune parameters HLA-DR expression on monocytes and endotoxin-induced cytokine production may carry prognostic value in cancer patients. Immunomodulating therapies leading to improvement of these parameters might in the future lead to increased options for treatment.

  9. Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy

    DEFF Research Database (Denmark)

    Larsson, S; Englund, M; Struglics, A

    2015-01-01

    concentrations of interleukin (IL)-6, -8 and tumor necrosis factor (TNF)-α by multiplex immunoassay, graded radiographic features of tibiofemoral and patellofemoral OA according to the Osteoarthritis Research Society International (OARSI) atlas, scored patient-reported outcomes using the Knee Injury.......07-2.09) in the preceding years. Subjects with increasing concentrations of IL-6 or TNF-α between examinations were five times more likely to have progressed in joint space narrowing between the same examinations, as compared to those with stable or decreasing concentrations (OR 5.17; 1.54-17.32 and 5.01; 1...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-15

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

  11. A Meta-analysis on the Effect of Ulinastatin on Serum Levels of C-Reactive Protein, Interleukin 6, and Tumor Necrosis Factor Alpha in Asian Patients with Acute Pancreatitis.

    Science.gov (United States)

    Zhang, Chunze; Wang, Yijia; Fu, Wenzheng; Zhang, Weihua; Wang, Tao; Qin, Hai

    2016-03-01

    We aimed to investigate the influence of ulinastatin (UTI) on the serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in Asian patients with acute pancreatitis (AP) by performance of a meta-analysis. Two investigators independently searched 11 databases, including PUBMED, EBSCO, Ovid, SpringerLink, Wiley, Web of Science, Cochrane Library, Wanfang database, China National Knowledge Infrastructure (CNKI), Chinese Journal Full-text Database, and China Biomedicine Database. The full-text articles were screened and the data were extracted using a standardized data extraction form. All statistical analyses were conducted with Stata software, version 12.0 (Stata Corporation, College Station, TX). A total of 94 studies were initially retrieved, and 10 studies containing 424 Asian patients with AP were ultimately enrolled in this meta-analysis. The results revealed that the serum levels of CRP, IL-6, and TNF-α in Asian AP patients significantly decreased after UTI therapy (CRP: standardized mean difference [SMD] = 3.26, 95% confidence interval [CI] = 1.69-4.83, p < 0.001; IL-6: SMD = 5.92, 95% CI = 2.09-9.75, p = 0.002; TNF-α: SMD = 4.07, 95% CI = 0.79-7.35, p = 0.015). The results of this meta-analysis suggest that UTI can effectively depress the serum levels of CRP, IL-6, and TNF-α in Asian patients with AP, and thereby inhibit inflammation.

  12. Responses of serum inflammatory factor high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha in elderly males with cerebral infarction Non-randomized concurrent control

    Institute of Scientific and Technical Information of China (English)

    Guiping Jiao; Xinjie Tan; Zhiliu Yuan; Chunling Li; Jing Wang; Wen Mo

    2008-01-01

    BACKGROUND: Cerebral infarction is poorly treated due to neuronal necrosis and secondary pathophysiological changes; for example, free radical production and inflammatory reactions.OBJECTIVE: To detect the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor nccrosis factor-α (TNF-α) in elderly males with cerebral infarction.DESIGN: Non-randomized current control study.SETTING: Cadre Medical Department, Guizhou Provincial People's Hospital.PARTICIPANTS: Forty elderly males (65-89 years old) with cerebral infarction were selected from Cadre Medical Department, Guizhou Provincial People's Hospital from February 2004 to December 2006. All patients met the diagnostic criteria of cerebral infarction modified at the 4th National Cerebrovascular Disease Academic Meeting, and were diagnosed on the basis of CT or MRI tests. Furthermore, 35 elderly male inpatients (65-87 years old) without cerebral infarction were selected as the control group. Included subjects provided confirmed consent and did not have heart disease, diabetes mellitus, lipid disorder, acute trauma, infection, rheumatism, or other inflammatory diseases. The study was approved by the local ethics committee. There were no significant differences in age, blood pressure, and lipid levels between the cerebral infarction group and the control group (P>0.05), and this suggested that the baseline data of both groups were comparable.METHODS: Fasting venous blood was drawn from cerebral infarction patients 24 hours after cerebral infarction attack and from control subjects 24 hours after hospitalization. A latex-enhanced immunoturbidimetric assay and an enzyme-linked immunosorbent assay were used to detect the levels of hs-CRP, IL-6, and TNF-α in the serum.MAIN OUTCOME MEASURES: The levels of hs-CRP, IL-6, and TNF-α in the serum in both groups.RESULTS: Forty cerebral infarction patients and thirty-five control subjects were included in the final analysis without any loss

  13. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNF alpha inhibitors

    DEFF Research Database (Denmark)

    Pedersen, S.J.; Hetland, M.L.; Sørensen, Inge Juul

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated......; etanercept, n = 8; and adalimumab, n = 3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6-12 weeks for up to 3 years. Patients with co-morbidities (n = 4), missing baseline samples (n = 3), and adverse events (n = 5) were...... excluded. Patients with SpA had compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 mu g/l (14-572) vs. 43 (20-184)), and MMP-3 (43 mu g/l (9.1-401) vs. 16 (2.5-47), p a parts per thousand currency signa...

  14. Remodeling of plasma lipoproteins in patients with rheumatoid arthritis: Interleukin-6 receptor-alpha inhibition with tocilizumab.

    Science.gov (United States)

    Lee, Janet S; Chapman, M John; Piraino, Paolo; Lamerz, Jens; Schindler, Thomas; Cutler, Paul; Dernick, Gregor

    2016-02-01

    Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, mediated in part by elevated circulating interleukin-6 levels and proinflammatory changes in plasma lipoproteins. We hypothesized that RA patients acquire inflammation-induced modifications to the protein cargo of circulating lipoproteins that may be reversed by tocilizumab, an interleukin-6 receptor-alpha inhibitor. Size-exclusion chromatography and reverse-phase protein arrays using 29 antibodies against 26 proteins were applied at baseline and after tocilizumab treatment to analyze the distributions of apolipoproteins, enzymes, lipid transfer proteins, and other associated proteins in plasma lipoprotein fractions from 20 women with RA. A 30% reduction in high-density lipoprotein (HDL)-associated serum amyloid A4 and complement C4 occurred with tocilizumab. Levels of C-reactive protein, associated or comigrating with HDL and low-density lipoprotein (LDL) peaks, were reduced on treatment by approximately 80% and 24%, respectively. Reductions in lipoprotein-associated phospholipase A2, lipoprotein (a), and cholesteryl ester transfer protein in the LDL fraction suggest reductions in LDL-associated proatherogenic factors. Elevations in very low-density lipoprotein (VLDL) enriched with apolipoprotein E were equally observed. Tocilizumab treatment led to reductions in proinflammatory components and proatherogenic proteins associated with HDL. Whether changes in the proteome of VLDL, LDL, and HDL induced by anti-inflammatory tocilizumab treatment in RA patients modify cardiovascular disease risk requires further investigation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Interleukin-6

    DEFF Research Database (Denmark)

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

    2011-01-01

    Human connective tissue, e.g., tendon, responds dynamically to physical activity, with collagen synthesis being increased after both acute and prolonged exercise or training. Markers of collagen synthesis and degradation as well as concentration of several potential growth factors have been shown...... to increase markedly in the peritendinous tissue around the human Achilles tendon following exercise. Of these potential growth factors interleukin-6 (IL-6) showed the largest fold increase, suggesting that IL-6 may be involved in transforming mechanical loading into collagen synthesis in human tendon tissue...... significantly stimulates collagen synthesis in the peritendinous tissue in humans. Exercise alone did not result in an increased collagen synthesis. This indicates that IL-6 is involved in the collagen synthesis and supports the hypothesis that IL-6 is an important growth factor of the connective tissue...

  16. Níveis de interleucina-6 e fator de necrose tumoral-alfa no liquor de recém-nascidos a termo com encefalopatia hipóxico-isquêmica Levels of interleukin-6 and tumor necrosis factor-alpha in the cerebrospinal fluid of full-term newborns with hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Silveira

    2003-08-01

    Full Text Available OBJETIVO: avaliar os níveis liquóricos de IL-6 e TNF-alfa em recém-nascidos a termo com encefalopatia hipóxico-isquêmica (EHI, comparando-os com os de recém-nascidos controles. METODOLOGIA: estudo caso-controle realizado no período de julho de 1999 a outubro de 2001, incluindo dois grupos de recém-nascidos a termo: controle, com 20 recém-nascidos sem sepse e/ou meningite e com escore de Apgar > 9 no primeiro e quinto minutos de vida; e casos, com 15 recém-nascidos asfixiados, caracterizados pelo escore de Apgar 3,0 mmol/l e necessidade de ventilação com pressão positiva pelo menos durante 2 minutos após o nascimento. Foram coletadas amostras de liquor nas primeiras 48 horas de vida, para determinação dos níveis de IL-6 e TNF-alfa pelo método de enzimoimunoensaio. RESULTADOS: os grupos não diferiram quanto ao peso de nascimento, idade gestacional, classificação quanto ao peso e idade gestacional, tipo de parto e tempo médio de obtenção do liquor; seus exames foram obtidos em média com 17 horas de vida. Nos recém-nascidos asfixiados, as medianas dos níveis liquóricos foram: 157,5 pg/ml para IL-6 e 14,7 pg/ml para TNF-alfa, significativamente mais elevadas que nos controles (IL-6: 4,1 pg/ml e TNF-alfa: 0,16 pg/ml. CONCLUSÕES: recém-nascidos a termo com EHI apresentaram níveis liquóricos de IL-6 e TNF-alfa mais elevados que controles, possivelmente devido à produção local cerebral dessas citocinas, especialmente o TNF-alfa. Estes achados estimulam estudos futuros, utilizando bloqueadores cerebrais das ações dessas citocinas como estratégia de neuroproteção.OBJECTIVE: to determine cerebrospinal fluid levels of interleukin-6 and tumor necrosis factor-alpha in full-term infants with hypoxic-ischemic encephalopathy, comparing with control infants. METHODS: controlled, prospective study, performed between July 1999 and October 2001 with two groups of full-term newborns: 20 controls with no sepsis and/or meningitis

  17. Ketamine inhibits tumor necrosis factor-alpha and interleukin-6 gene expressions in lipopolysaccharide-stimulated macrophages through suppression of toll-like receptor 4-mediated c-Jun N-terminal kinase phosphorylation and activator protein-1 activation.

    Science.gov (United States)

    Wu, Gone-Jhe; Chen, Ta-Liang; Ueng, Yune-Fang; Chen, Ruei-Ming

    2008-04-01

    Our previous study showed that ketamine, an intravenous anesthetic agent, has anti-inflammatory effects. In this study, we further evaluated the effects of ketamine on the regulation of tumor necrosis factor-alpha (TNF-alpha) and interlukin-6 (IL-6) gene expressions and its possible signal-transducing mechanisms in lipopolysaccharide (LPS)-activated macrophages. Exposure of macrophages to 1, 10, and 100 microM ketamine, 100 ng/ml LPS, or a combination of ketamine and LPS for 1, 6, and 24 h was not cytotoxic to macrophages. A concentration of 1000 microM of ketamine alone or in combined treatment with LPS caused significant cell death. Administration of LPS increased cellular TNF-alpha and IL-6 protein levels in concentration- and time-dependent manners. Meanwhile, treatment with ketamine concentration- and time-dependently alleviated the enhanced effects. LPS induced TNF-alpha and IL-6 mRNA syntheses. Administration of ketamine at a therapeutic concentration (100 microM) significantly inhibited LPS-induced TNF-alpha and IL-6 mRNA expressions. Application of toll-like receptor 4 (TLR4) small interfering (si)RNA into macrophages decreased cellular TLR4 levels. Co-treatment of macrophages with ketamine and TLR4 siRNA decreased the LPS-induced TNF-alpha and IL-6 productions more than alone administration of TLR4 siRNA. LPS stimulated phosphorylation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos from the cytoplasm to nuclei. However, administration of ketamine significantly decreased LPS-induced activation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos. LPS increased the binding of nuclear extracts to activator protein-1 consensus DNA oligonucleotides. Administration of ketamine significantly ameliorated LPS-induced DNA binding activity of activator protein-1. Therefore, a clinically relevant concentration of ketamine can inhibit TNF-alpha and IL-6 gene expressions in LPS-activated macrophages. The suppressive mechanisms occur through

  18. INTERLEUKIN-6, INTERLEUKIN-8 AND TUMOR NECROSIS FACTOR-α EXPRESSION IN ULCERATIVE COLITIS

    Institute of Scientific and Technical Information of China (English)

    李琪佳; 宫恩聪; 刘叔平; 鄂文

    2001-01-01

    Objectve To study the new insight into the pathogenesis of ulcerative colitis. Methods Interleukin-6 (IL-6), Interleukin-8 (IL-8) and tumor necrosis factor-α(TNF-α) mRNA expression were assessed in the intestinal mucosa of active (n=32) and inactive (n=18) phase using in situ hybridization. Immunohistochemistry for different leukocyte subsets was performed in biopsy specimens of the intestinal mucosa from 50 patients with ulcerative colitis and 5 healthy controls.

  19. Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells: synergy with interleukin-1beta and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Andresen, Lars; Alvarez, Susana

    2006-01-01

    Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development,...

  20. Interleukin-6 and ratio of plasma interleukin-6/interleukin-10 as risk factors of symptomatic lumbar osteoarthritis

    Science.gov (United States)

    Suyasa, I Ketut; Kawiyana, I Ketut Siki; Bakta, I Made; Widiana, I Gde Raka

    2017-01-01

    AIM To determine the role of cartilage oligomeric matrix protein (COMP), interleukin (IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis (OA) in postmenopausal women with estrogen deficiency. METHODS Case-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS From 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk (OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA (cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk (OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6 (cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA (OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10 (cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk (OR = 3.4; 95%CI: 1.204-11.787; P = 0.011) for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level (cut-off point 0.364). CONCLUSION High ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency. PMID:28251065

  1. Interleukin-5, interleukin-6, interleukin-8 and tumour necrosis factor-alpha levels obtained within 24-h of admission do not predict high-risk infection in children with febrile neutropenia

    Directory of Open Access Journals (Sweden)

    R Aggarwal

    2013-01-01

    Full Text Available Purpose: Biomarkers that can predict the severity of febrile neutropenia (FN are potential tools for clinical practice. Objective: The objective of this study is to evaluate the reliability of plasma interleukin (IL levels as indicators of high-risk FN. Materials and Methods: Children with haematological malignancies and FN were enrolled prospectively. A blood sample was obtained within 24-h of admission for estimation of IL-5, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-α level by the enzyme-linked immunosorbent assay. Patients were stratified into three groups. Group I (low-risk: No focus of infection; Group II: Clinical/radiological focus of infection; Group III: Microbiologically proven infection or FN related mortality. Groups II and III were analysed as high-risk. The cytokines were assessed at three different cut-off levels. Results: A total of 52 episodes of FN in 48 patients were evaluated. The mean age was 6 years (range: 2-13. Primary diagnosis included acute lymphoblastic leukaemia (82%, non-Hodgkin′s lymphoma (13% and acute myeloid leukaemia (5%. Absolute neutrophil count was < 200 cells/μl in half and 200-500 in 23%. Majority were categorised as Group I (69%, followed by Group II (16% and III (15%. The range of IL-5 was too narrow and similar in the two risk-groups to be of any relevance. The best sensitivity of TNF-α and IL-6 for high-risk group was 78% and 70%, respectively. The highest specificity observed was 35%. The negative predictive value of IL-6, IL-8 and TNF-α exceeded 80%. Conclusion: IL-5, IL-6, IL-8 and TNF-α failed as predictors of clinically localised or microbiologically documented infection in children with chemotherapy induced FN. However, IL-6, IL-8 and TNF-α could be useful in excluding the possibility of high-risk infection.

  2. The Interleukin-6 and vascular endothelial growth factor in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Negar Azarpira

    2012-01-01

    Full Text Available We studied the correlation between changes in the serum levels of vascular endothelial growth factor (VEGF and interleukin-6 (IL-6 with complications such as acute graft versus host disease (aGVHD, veno-occlusive disease (VOD or occurrence of infection after hematopoietic stem cell transplantation (HSCT. Serum VEGF and IL-6 levels were sequentially measured by enzyme-linked immunosorbant assay (ELISA in 35 patients who had undergone HSCT. Serum levels of IL-6 in patients with aGVHD were increased in comparison with patients without aGVHD, but the difference was not statistically significant. Serum levels of VEGF were only increased in patients with aGVHD during the early days after transplantation. No signi-ficantly altered levels of IL-6 and VEGF were observed in patients with VOD or sepsis. These results demonstrate that rising levels of VEGF and IL-6 may be good and specific biomarkers for transplant aGVHD.

  3. Interferon-alpha in viral and bacterial gastroenteritis: a comparison with C-reactive protein and interleukin-6.

    Science.gov (United States)

    Mangiarotti, P; Moulin, F; Palmer, P; Ravilly, S; Raymond, J; Gendrel, D

    1999-06-01

    The aim of the study was to identify serum markers able to differentiate bacterial and viral origin in acute diarrhoea. Interferon-alpha (INF-alpha), C-reactive protein (CRP) and interleukin-6 were determined on admission in the sera of 119 children aged between 1 mo and 14 y who were hospitalized for rotavirus (n = 60) or bacterial diarrhoea (Salmonella spp. 39 cases, Shigella spp. 15 cases, Campylobacter jejuni 5 cases). CRP concentration was >10 mg/l in 48.3% of children with viral gastroenteritis and 86.4% of children with bacterial gastroenteritis. IL6 concentration was >100 pg/ml in 11.7% and 26.3% of cases, respectively. INF-alpha was detected in 79.1% of children with rotavirus (sens 79%) and in 3.5% (spec 93%) with bacterial gastroenteritis. However the INF-alpha assay takes 48 h and pathogens are often identified from stools before interferon results are available. We found that serum markers are not discriminating enough to differentiate between viral and bacterial gastroenteritis in emergency cases.

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

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Shiga

    2016-01-01

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

  5. Magnesium alloy modified by micro-arc oxidation can influence tumor necrosis factor-alpha and interleukin-6 production in macrophages%微弧氧化镁合金对巨噬细胞肿瘤坏死因子和白细胞介素6的影响

    Institute of Scientific and Technical Information of China (English)

    庄岩; 吴锋; 孟改利; 李晓会

    2013-01-01

      背景:微弧氧化处理可提高镁合金的抗腐蚀性能,延缓其降解速率。目的:观察微弧氧化处理镁合金对小鼠巨噬细胞肿瘤坏死因子α和白细胞介素6的影响。方法:在小鼠RAW264.7细胞中分别加入镁合金浸提液(对照组)、微弧氧化处理镁合金浸提液(实验组)及RPMI-1640(空白对照组),1 h后加入脂多糖,作用24 h后,收集细胞上清液,检测肿瘤坏死因子α和白细胞介素6水平,MTT法测定脂多糖刺激前后的RAW264.7细胞活性。结果与结论:①脂多糖刺激前的RAW264.7细胞活性:对照组>实验组>空白对照组(P均0.05)。③脂多糖刺激后RAW264.7细胞白细胞介素6与肿瘤坏死因子α的表达量:对照组白细胞介素6表达量明显高于实验组和空白对照组(P 0.05)。表明微弧氧化处理镁合金对小鼠巨噬细胞活性无明显影响,同时降低了炎性反应。%BACKGROUND: Micro-arc oxidation treatment can improve the corrosion resistance of the magnesium alloy and delay the degradation rate. OBJECTIVE: To investigate the effects of magnesium alloy with micro-arc oxidation treatment on tumor necrosis factor-alpha and interleukin-6 expression in mouse macrophage RAW264.7 cells. METHODS: Extracts of magnesium alloy, magnesium alloy with micro-arc oxidation treatment or RPMI-1640 medium were added to RAW24.7 cells at 1 hour prior to lipopolysaccharide treatment for 24 hours. Then culture supernatants were col ected for measuring the concentrations of tumor necrosis factor-alpha and interleukin-6, and cel proliferation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. RESULTS AND CONCLUSION: Lipopolysaccharide could significantly increase RAW264.7 cel viability. However, there was no significant difference in lipopolysaccharide-induced RAW264.7 cel viability among the three groups (P > 0.05). But the cel viability in the blank control group was significantly increased

  6. Interleukin-6 gene promoter polymorphisms and cardiovascular risk factors. A family study.

    Science.gov (United States)

    Guzmán-Guzmán, Iris Paola; Muñoz-Valle, José Francisco; Flores-Alfaro, Eugenia; Salgado-Goytia, Lorenzo; Salgado-Bernabé, Aralia Berenice; Parra-Rojas, Isela

    2010-01-01

    Interleukin-6 (IL-6) is a cytokine involved in inflammatory process, as well as in glucose and lipid metabolism. Several studies of the biological relevance of IL-6 gene polymorphisms have indicated a relationship with cardiovascular disease. The aim of this study was to assess whether the -174 G/C and -572 G/C of IL-6 gene polymorphisms are associated with cardiovascular risk factors in Mexican families. Ninety members of 30 Mexican families, in which an index case (proband) had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical and hematological parameters. High sensitivity C- reactive protein levels were measurement for nephelometric analysis. Screening for both polymorphisms studied was performed by PCR-RFLP. In the parents, both polymorphisms were in Hardy-Weinberg's equilibrium. The genotypes -174 GC/CC were associated with T2D (OR=1.23, IC(95%) 1.01-1.5) and highest levels of hsCRP (p=0.02), whereas genotype -572 GG was associated with T2D (OR=1.24, IC(95%) 1.04-1.47) with an inflammatory state determined by the increase in the leukocyte count (OR=1.24, IC(95%) 1.02-1.51). The genotypes -174 GC/CC and -572 GG may confer susceptibility for the development of subclinical inflammation and type 2 diabetes in Mexican families.

  7. Immobilization increases interleukin-6, but not tumour necrosis factor-a, release from the leg during exercise in humans

    DEFF Research Database (Denmark)

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

    2013-01-01

    Data on interleukin-6 (IL-6) and tumour necrosis factor-a (TNF-a) release during acute exercise are not conclusive, and information is lacking about the impact of physical inactivity. Some studies have shown an increase, but others report no changes in IL-6 and TNF-a release during exercise. We...

  8. Interleukin-6

    DEFF Research Database (Denmark)

    Reihmane, Dace; Dela, Flemming

    2014-01-01

    as anti-inflammatory properties of IL-6. Since the first report of acute exercise-induced increase in plasma IL-6 in the early 1990s, scientists have tried to elucidate the factors that influence the magnitude of change of plasma IL-6, as well as the possible biological roles of this cytokine. Evidence...... suggests that exercise intensity and duration as well as the form of contraction (e.g., eccentric or concentric) and muscle damage all influence IL-6 response to acute exercise. However, data on training status and performance on plasma IL-6 concentration changes during exercise are more inconclusive......, as discussed in this review. In the last decade, most of the studies have focused on IL-6 as an 'energy sensor' possibly secreted by skeletal muscle that activates glycogenolysis in the liver and lipolysis in fat tissue in order to provide muscle with the growing energy demands during exercise....

  9. Wnt3a regulates tumor necrosis factor-α-stimulated interleukin-6 release in osteoblasts.

    Science.gov (United States)

    Natsume, Hideo; Tokuda, Haruhiko; Adachi, Seiji; Matsushima-Nishiwaki, Rie; Kato, Kenji; Minamitani, Chiho; Otsuka, Takanobu; Kozawa, Osamu

    2011-01-01

    It is recognized that Wnt pathways regulate bone metabolism. We have previously shown that tumor necrosis factor-α (TNF-α) stimulates synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, via p44/p42 mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3-kinase)/Akt in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of Wnt3a on TNF-α-stimulated IL-6 synthesis in these cells. Wnt3a, which alone did not affect the IL-6 levels, significantly suppressed the TNF-α-stimulated IL-6 release. Lithium Chloride (LiCl), which is an inhibitor of GSK3β, markedly reduced the TNF-α-stimulated IL-6 release, similar to the results with Wnt3a. The suppression by Wnt3a or LiCl was also observed in the intracellular protein levels of IL-6 elicited by TNF-α. Wnt3a failed to affect the TNF-α-induced phosphorylation of p44/p42 MAP kinase, Akt, IκB or NFκB. Either Wnt3a or LiCl failed to reduce, rather increased the IL-6 mRNA expression stimulated by TNF-α. Lactacystin, a proteasome inhibitor, and bafilomycin A1, a lysosomal protease inhibitor, significantly restored the suppressive effect of Wnt3a on TNF-α-stimulated IL-6 release. Taken together, our results strongly suggest that Wnt3a regulates IL-6 release stimulated by TNF-α at post-transcriptional level in osteoblasts.

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

    Directory of Open Access Journals (Sweden)

    Iris Paola Guzmán-Guzmán

    2010-01-01

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

  11. The Change of Interleukin-6 and Tumor Necrosis Factor in Patients with Obstructive Sleep Apnea Syndrome

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The levels of lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression in culture of peripheral blood mononuclear cells (PBMC) and the plasma levels of IL-6 and TNF-α in the patients with obstructive sleep apnea syndrome (OSAS) were measured and the relationship between OSAS and IL-6 or TNF-α expression studied. Both IL-6 and TNF-α were detected by using ELISA in 22 patients with OSAS and 16 normal controls. The levels of LPS-induced IL-6 (787.82±151.97 pg/ml) and TNF-α (4165.45±1501.43 pg/ml) expression in the supernatant of the culture of PBMC and plasma level of IL-6 (50.67±4.70 pg/ml) and TNF-α (299.09±43.57 pg/ml) in the patients with OSAS were significantly higher than those in the normal controls (in the supernatant of the culture of PBMC: 562.69±197.54 pg/ml and 1596.25±403.08 pg/ml respectively; in the plasma: 12.69±2.75 pg/ml and 101.88±21.27 pg/ml respectively). There were significantly positive correlation between the levels of IL-6 and TNF-α and the percentage of time of apnea and hyponea, as well as the percentage of time spending at SaO2 below 90 % in the total sleep time. It was concluded that LPS-induced IL-6 and TNF-α levels as well as plasma IL-6 and TNF-α levels in the patients with OSAS were up-regulated, which may be associated with the pathogenesis of OSAS.

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

    Directory of Open Access Journals (Sweden)

    Dimitriades-Schmutz Beatrice

    2009-02-01

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

  13. The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells.

    Science.gov (United States)

    Rawstron, A C; Fenton, J A; Ashcroft, J; English, A; Jones, R A; Richards, S J; Pratt, G; Owen, R; Davies, F E; Child, J A; Jack, A S; Morgan, G

    2000-12-01

    Interleukin-6 (IL-6) is reported to be central to the pathogenesis of myeloma, inducing proliferation and inhibiting apoptosis in neoplastic plasma cells. Therefore, abrogating IL-6 signaling is of therapeutic interest, particularly with the development of humanized anti-IL-6 receptor (IL-6R) antibodies. The use of such antibodies clinically requires an understanding of IL-6R expression on neoplastic cells, particularly in the cycling fraction. IL-6R expression levels were determined on plasma cells from patients with myeloma (n = 93) and with monoclonal gammopathy of undetermined significance (MGUS) or plasmacytoma (n = 66) and compared with the levels found on normal plasma cells (n = 11). In addition, 4-color flow cytometry was used to assess the differential expression by stage of differentiation and cell cycle status of the neoplastic plasma cells. IL-6R alpha chain (CD126) was not detectable in normal plasma cells, but was expressed in approximately 90% of patients with myeloma. In all groups, the expression levels showed a normal distribution. In patients with MGUS or plasmacytoma, neoplastic plasma cells expressed significantly higher levels of CD126 compared with phenotypically normal plasma cells from the same marrow. VLA-5(-) "immature" plasma cells showed the highest levels of CD126 expression, but "mature" VLA-5(+) myeloma plasma cells also overexpressed CD126 when compared with normal subjects. This study demonstrates that CD126 expression is restricted to neoplastic plasma cells, with little or no detectable expression by normal cells. Stromal cells in the bone marrow microenvironment do not induce the overexpression because neoplastic cells express higher levels of CD126 than normal plasma cells from the same bone marrow in individuals with MGUS. (Blood. 2000;96:3880-3886)

  14. Naringin Inhibits Tumor Growth And Reduces Interleukin-6 And Tumor Necrosis Factor α Levels In Rats With Walker 256 Carcinosarcoma

    OpenAIRE

    Camargo C.A.; Gomes-Marcondes M.C.C.; Wutzki N.C.; Aoyama H.

    2012-01-01

    The flavonoid naringin is a polyphenolic compound that naturally occurs in citrus. Patients with cancer generally present features of malnutrition and cachexia. Levels of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) are raised in patients with cancer. This study was designed to analyze the in vivo effect of naringin in the therapeutic treatment of rats bearing Walker 256 carcinosarcoma (W256). Rats were treated intraperitoneally with different doses o...

  15. A non-canonical function of eukaryotic elongation factor 1A1: regulation of interleukin-6 expression.

    Science.gov (United States)

    Schulz, Ingo; Engel, Claudia; Niestroj, André J; Kehlen, Astrid; Rahfeld, Jens-Ulrich; Kleinschmidt, Martin; Lehmann, Karola; Roßner, Steffen; Demuth, Hans-Ulrich

    2014-05-01

    Interleukin-6 is one of the most prominent triggers of inflammatory processes. We have shown recently that heteroarylketones (HAKs) interfere with stimulated interleukin-6 expression in astrocytes by suppression of STAT3 phosphorylation at serine 727. Surprisingly, this effect is not based on the inhibition of STAT3-relevant kinases. Therefore, we here used the structurally modified HAK compound biotin-HAK-3 in a reverse chemical approach to identify the relevant molecular target in UV-mediated cross-linking experiments. Employing streptavidin-specific 2D-immunoblotting followed by mass spectrometry we identified nine proteins putatively interacting with biotin-HAK-3. After co-immunoprecipitation, co-immunofluorescence, surface plasmon resonance analyses and RNAi-mediated knock-down, the eukaryotic elongation factor 1A1 (eEF1A1) was verified as the relevant target of HAK bioactivity. eEF1A1 forms complexes with STAT3 and PKCδ, which are crucial for STAT3(S727) phosphorylation and for NF-κB/STAT3-enhanced interleukin-6 expression. Furthermore, the intracellular HAK accumulation is strongly dependent on eEF1A1 expression. Taken together, the results reveal a novel molecular mechanism for a non-canonical role of eEF1A1 in signal transduction via direct modulation of kinase-dependent phosphorylation events.

  16. 慢性乙醇中毒患者血清IL-6,TNF-α水平与脑萎缩的相关性%Correlation of brain atrophy with the levels of serum interleukin-6 and tumor necrosis factor alpha in chronic alcoholism patients

    Institute of Scientific and Technical Information of China (English)

    徐平; 吴岳洲; 雷显泽; 张骏; 胡泳涛

    2004-01-01

    BACKGROUND: Alcoholism can lead to wide and serious damages in nervoussystem and could reduce the responses of natural killer cells that can induce thechanges in cell-mediated immunity. However, studies on the relationship be-tween the immune injury in alcoholism and cerebral injury are rare.OBJECTIVE: To discuss the relationship between the changes in the serumlevels of interleukin-6(IL-6) and tumor necrosis factor alpha(TNF-α) andbrain atrophy caused by alcoholism.DESIGN: A case-control study.SETTINGS and PARTICIPANTS: The study was completed in the FirstAffiliated Hospital of Zunyi Medical University. Thirty-two chronic alcoholismpatients were selected from outpatient and inpatient department from Febru-ary 1999 to July 2001, and all of them were males aged from 24 to 64 yearswith an onset age from 24 to 50 years and courses of disease from 2 months to6 years. Thirty healthy males were selected in the control group with an agefrom 30 to 60 years old.INTERVENTIONS: Serum levels of IL-6 and TNF-α were detected by dou-bie-antibody ELISA, which was combined with cranial CT scanning for analysis.MAIN OUTCOME MEASURES: The severity of brain atrophy was deter-mined by the index of ventricle, Huckman value, index of somatic part of lat-eral ventricle and the width of the three ventricles. Corresponding serum IL-6and TNF-α strengths were calculated by standard curve of reagent box.group were(286. 31 ± 104.79) ng/L and(413.34 ±66.87) ng/L respec-tively, which were significantly higher than those of the control group[ (205.43 ± 48.67) ng/L and (261.36 ± 51.48) ng/L respectively] ( P <atrophy patients were(343.75 ±99.59) ng/L and(449.38 ±55.79) ng/Lrespectively, which were significantly higher than those of non - brain atrophypatients[ (228. 88 ± 75.74) ng/L and(337.31 ± 57.96) ng/L respectively]( P < 0. 001 ) . The serum level of TNF-α in chronic alcoholism patientswithout brain atrophy was significantly higher than that of the control groupcorrelated with

  17. Role of interaction between variants in the PPARG and interleukin-6 genes on obesity related metabolic risk factors.

    Science.gov (United States)

    Barbieri, M; Rizzo, M R; Papa, M; Acampora, R; De Angelis, L; Olivieri, F; Marchegiani, F; Franceschi, C; Paolisso, G

    2005-07-01

    The combined effect of Peroxisome proliferator-activated receptor gamma (PPARG) Pro/Ala and interleukin-6 G174C gene variants, was evaluated in 429 Caucasian subjects in order to determine whether subjects carrying both variants were at different risk for obesity. In particular, the combined contribution of these two variants (both independent and interaction effects) to the total variation of obesity-related factors was estimated. All subjects were genotyped for codon 12 Pro/Ala locus variability and for the interleukin-6-174 C/G promoter polymorphism. Subjects with the Ala variant had significantly lower BMI, insulin resistance, triglyceride levels than those without. Furthermore, subjects with Ala variant had significantly lower IL-6 levels (0.88 +/- 0.9 vs 1.61 +/- 2.25 pg/ml; p = 0.041). In contrast, the IL6-C variant was significantly associated with lower plasma IL-6 and with lower total cholesterol levels but was not significantly associated with any other obesity risk factors. Indeed, subjects carrying both PPARG and IL-6 gene variants, had a clearly more favourable profile of obesity related risk factors than subjects with one variant, having Ala+/C+ carriers lower BMI (22.8 +/- 2.3 vs 24.14 +/- 1.9; f = 5.31; p obesity related' factors is additive.

  18. Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects

    National Research Council Canada - National Science Library

    Jonge, de, E; Friederich, P.W; Vlasuk, G.P; Rote, W; Vroom, M.B; Levi, M.M; Poll, van der, T

    2003-01-01

    .... Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma...

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

    Directory of Open Access Journals (Sweden)

    Toledo JO

    2015-01-01

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

  20. Elevated plasma levels of TNF-alpha and Interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders

    Directory of Open Access Journals (Sweden)

    Ellinghaus Peter

    2009-11-01

    Full Text Available Abstract Background Diabetes mellitus (DM has reached epidemic proportions and is an important risk factor for heart failure (HF. Left ventricular diastolic dysfunction (LVDD is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6 and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease. Methods We enrolled 41 consecutive patients (mean age 65+/-10 years submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E transmitral flow velocity was measured. LVDD was defined as E/Em ratio ≥ 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes. Results Patients with E/Em ratio ≥ 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline had significantly higher IL-6 (P = 0,001, TNF-alpha (P Conclusion This study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.

  1. Acurácia diagnóstica do leucograma, proteína C-reativa, interleucina-6 e fator de necrose tumoral-alfa na sepse neonatal tardia Accuracy of white blood cell count, C-reactive protein, interleukin-6 and tumor necrosis factor alpha for diagnosing late neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Jamil P. S. Caldas

    2008-12-01

    Full Text Available OBJETIVO: Avaliar o valor do leucograma, proteína C-reativa (PCR, interleucina-6 (IL-6 e do fator de necrose tumoral-alfa (TNF-α, isoladamente e em conjunto, na detecção da sepse neonatal tardia. MÉTODOS: Estudo de validação diagnóstica. A PCR, IL-6 e TNF-α foram dosados por quimioluminescência à suspeita clínica, 24 e 48 horas depois, e o leucograma unicamente à suspeita. De acordo com evolução clínica e resultados de culturas, três grupos foram definidos: sepse comprovada (SC, sepse provável (SP e não infectados (NI. Os testes estatísticos utilizados foram os de Wilcoxon, qui-quadrado e análise de variância de Friedman e os limites de corte foram obtidos pela construção da curva ROC. RESULTADOS: Estudaram-se 82 crianças, sendo 42 no grupo SC, 16 no SP e 24 NI. Nos três momentos, as medianas da PCR e da IL-6 mostraram-se significativamente mais elevadas nos grupos SC e SP, e as do TNF-α alteraram-se apenas no grupo SC. Os índices diagnósticos da PCR foram elevados nos três momentos e com acurácia superior a do leucograma e semelhante a da IL-6 e a do TNF-α em suas primeiras medidas. Entre as citocinas, não houve diferença estatística entre elas, nem em relação ao leucograma. A associação dos testes não aumentou a capacidade diagnóstica, exceto na combinação entre leucograma e PCR2 e na dosagem seriada de PCR. CONCLUSÕES: A PCR e o leucograma mostram-se úteis no diagnóstico de sepse neonatal tardia e comparáveis à IL-6 e ao TNF-α. A acurácia aumentou com a associação PCR-leucograma e a dosagem seriada da PCR.OBJECTIVE: To evaluate the diagnostic value for late neonatal sepsis of white blood cell count (WBC and assays for C-reactive protein (CRP, interleukin-6 (IL-6 and tumor necrosis factor alpha (TNF-α, in isolation and in conjunction. METHODS: This was a diagnostic test validation study. Chemiluminescence was used to assay CRP, IL-6 and TNF-α at the time of clinical suspicion and again

  2. Interleukin-6 and tumor necrosis factor in the pathogenesis of adverse reactions after treatment of lymphatic filariasis and onchocerciasis.

    Science.gov (United States)

    Turner, P F; Rockett, K A; Ottesen, E A; Francis, H; Awadzi, K; Clark, I A

    1994-05-01

    Adverse reactions following treatment of onchocerciasis and bancroftian filariasis are common and frequently severe. They are generally caused not by direct drug toxicity but by host inflammatory responses to dying microfilariae. To define the responsible mechanism, serial blood levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were studied in 15 microfilaria-positive patients (10 with bancroftian filariasis, 5 with onchocerciasis) and 4 microfilaria-negative persons after diethylcarbamazine treatment. Elevations in IL-6 correlated with the occurrence and severity of clinical symptoms after treatment; for the onchocerciasis patients IL-6 levels directly reflected pretreatment intensity of infection. Serum TNF levels also rose but did not correlate directly with infection intensity or reaction severity. Microfilaria-negative controls remained asymptomatic with no significant rise in either cytokine. These findings suggest an etiologic role for systemically elevated cytokines in the inflammatory reactions developing after treatment of filarial infections in humans.

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

    Directory of Open Access Journals (Sweden)

    Renata Mozrzymas

    2016-06-01

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

  4. Serum and urinary interleukin-6 (IL-6) levels as predicting factors of Kawasaki disease activity.

    Science.gov (United States)

    Chow, Y M; Lin, C Y; Hwang, B

    1993-01-01

    From January 1988 to Autumn 1991, 60 patients suffering from Kawasaki disease (KD) were recruited in this study. Their ages ranged from 4 months to 5 years. Diagnosis was based on the criteria revised in 1984 by the KD Research Committee in Japan. Of these, 12 cases developed coronary aneurysms. First, blood samples from 60 KD patients were taken on admission before aspirin and/or intravenous immunoglobulin (IVIG) treatment. Convalescent blood samples were taken 3 months after onset of disease. The control group included (1) 10 cases of viral infection with skin rash and fever (aged 5 months to 5 years) and (2) 10 age and sex matched normal children admitted for elective pediatric surgery such as inguinal hernia. Second, urinary samples were collected from 32 cases during the acute phase of KD. Of these, 10 cases had pyuria and/or proteinuria. The results showed that the serum IL-6 levels from KD patients during the first week of acute phase were significantly increased while undetectable in the convalescent sera and controls. There was also a statistical difference between the with and without coronary aneurysm groups during the first week (336.8 +/- 95.1 vs 125.5 +/- 56.5 pg/ml, P Urinary IL-6 levels were significantly elevated in KD patients with pyuria and/or proteinuria (156.6 +/- 77.7 pg/mg Cr) and undetectable in the group without pyuria and proteinuria and controls during the first week. There was no difference between with and without coronary aneurysm. These results suggest that serum IL-6 level is a useful factor for predicting formation of coronary aneurysm even within one week after onset of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Clinical signs, symptoms and serum level of interleukin-6 and tumor necrosis factor in women with or without endometriosis

    Institute of Scientific and Technical Information of China (English)

    Wachyu Hadisaputra

    2013-01-01

    Objective: To evaluate clinical signs and symptoms and serum levels of interleukin-6 ( IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF) as non-invasive methods to diagnose endometriosis. Methods: Eighty women scheduled to laparoscopy underwent blood sampling for measurement of IL-6, TNF-α, MMP-2, and VEGF. The diagnosis of endometriosis was established by laparoscopy using The American Fertility Society visual diagnosis. The presence or absence of endometriosis was correlated with clinical signs and symptoms and with serum levels of those substances. Results:The sensitivity and specificity to detect endometriosis of infertility (OR 134.3) were 78 % and 98%, dysmenorrhoea (OR 11.7) were 63 % and 88 %, and chronic pelvic pain (OR 13.0) were 28 % and 100 %. The presence of rectovaginal nodules had a sensitivity 25 % and specificity 100 %. (OR 11.3, 95 %). The sensitivity and specificity of biologic markers IL-6 (OR 2.5) were 68 % and 53%, and TNF-α (OR 28.1) were 68% and 60 %. Conclusions: History of infertility, dysmenorrhea, chronic pelvic pain, dyspareunia, cervical tenderness and rectovaginal nodule are clinical signs and symptoms suggesting endometriosis. IL-6 and TNF-α appears to be best serum markers for endometriosis.

  6. Lipopolysaccharide induces visceral hypersensitivity: role of interleukin-1, interleukin-6, and peripheral corticotropin-releasing factor in rats.

    Science.gov (United States)

    Nozu, Tsukasa; Miyagishi, Saori; Nozu, Rintaro; Takakusaki, Kaoru; Okumura, Toshikatsu

    2017-01-01

    Lipopolysaccharide (LPS) induces visceral hypersensitivity, and corticotropin-releasing factor (CRF) also modulates visceral sensation. Besides, LPS increases CRF immunoreactivity in rat colon, which raises the possibility of the existence of a link between LPS and the CRF system in modulating visceral sensation. The present study tried to clarify this possibility. Visceral sensation was assessed by abdominal muscle contractions induced by colonic balloon distention, i.e., visceromotor response, electrophysiologically in conscious rats. The threshold of visceromotor response was measured before and after administration of drugs. LPS at a dose of 1 mg/kg subcutaneously (sc) decreased the threshold at 3 h after the administration. Intraperitoneal (ip) administration of anakinra (20 mg/kg), an interleukin-1 (IL-1) receptor antagonist, or interleukin-6 (IL-6) antibody (16.6 µg/kg) blocked this effect. Additionally, IL-1β (10 µg/kg, sc) or IL-6 (10 µg/kg, sc) induced visceral allodynia. Astressin (200 µg/kg, ip), a non-selective CRF receptor antagonist, abolished the effect of LPS, but astressin2-B (200 µg/kg, ip), a CRF receptor type 2 (CRF2) antagonist, did not alter it. Peripheral CRF receptor type 1 (CRF1) stimulation by cortagine (60 µg/kg, ip) exaggerated the effect of LPS, but activation of CRF2 by urocortin 2 (60 µg/kg, ip) abolished it. LPS induced visceral allodynia possibly through stimulating IL-1 and IL-6 release. In addition, this effect was mediated through peripheral CRF signaling. Since the LPS-cytokine system is thought to contribute to altered visceral sensation in the patients with irritable bowel syndrome, these results may further suggest that CRF plays a crucial role in the pathophysiology of this disease.

  7. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

    LENUS (Irish Health Repository)

    Bull, S J

    2009-12-01

    Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King\\'s College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The \\'low IL-6\\' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The \\'high transcription\\' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the \\'protective\\' effect of the 5-HTTLPR polymorphism was evident only in the presence of the \\'low IL-6\\' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the \\'high IL-6\\' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role

  8. Dynamic changes of interleukin-1, interleukin-6 and tumor necrosis factor in i ntermingled skin graft in burned rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To compare the dynamic changes of int erleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) in intermingled skin graft with those in other types of skin grafts in rats.   Methods: A 10%-15% third-degree burn was created in 180 Spreg ue-Dawley (SD) rats. After removing the scar, skin grafts were performed on the open wounds immediately with autoskin (aus, n=54), allosk in (als, n=54) and intermingled skin (n=36). That is to say, in the intermingled skin graft, a big piece of alloskin (mals) was grafted first, and 3 days later, small pieces of autoskin (maus) wer e embedded in the alloskin. The rest 36 rats were taken as the controls. And the biological activities of IL-1, IL-6 and TNF in graft sheets in each group wer e detected after skin graft.   Results: The levels of IL-1, IL-6 and TNF in the aus group de creased steadily after their initial elevations, whereas in the als group they i ncreased significantly and kept on the peak level in the later phases. In the in termingled group, there appeared a lowest IL-1 level in the mals and a highest one in the maus simultaneously at 7 (4) days (The number out of parenthesis is t he days after transplanting with alloskin sheets, and the number in parenthesis is the days after embedding autoskin sheets in the intermingled skin graft. Simi larly hereinafter.) after skin graft (P<0.01), and the high level in the maus abruptly decreased at 14 (11) days after skin graft. At exactly the same phase on day 7 (4), a prominent peaked IL-6 in the mals occurr ed. In the later phases, the levels of TNF remained relatively low both in the m als and in the maus. From day 7 (4) on, each cytokine fluctuation in the mals sy nchronized with that in the maus. The longer the post transplantation period las ted, the more the positive cytokine correlated between the mals and the maus.   Conclusions: The low levels of IL-1 and TNF may be important f actors to lighten the intensity of local

  9. Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells.

    Science.gov (United States)

    Podar, Klaus; Tai, Yu-Tzu; Cole, Craig E; Hideshima, Teru; Sattler, Martin; Hamblin, Angela; Mitsiades, Nicholas; Schlossman, Robert L; Davies, Faith E; Morgan, Gareth J; Munshi, Nikhil C; Chauhan, Dharminder; Anderson, Kenneth C

    2003-02-21

    Caveolae, specialized flask-shaped lipid rafts on the cell surface, are composed of cholesterol, sphingolipids, and structural proteins termed caveolins; functionally, these plasma membrane microdomains have been implicated in signal transduction and transmembrane transport. In the present study, we examined the role of caveolin-1 in multiple myeloma cells. We show for the first time that caveolin-1, which is usually absent in blood cells, is expressed in multiple myeloma cells. Analysis of myeloma cell-derived plasma membrane fractions shows that caveolin-1 is co-localized with interleukin-6 receptor signal transducing chain gp130 and with insulin-like growth factor-I receptor. Cholesterol depletion by beta-cyclodextrin results in the loss of caveola structure in myeloma cells, as shown by transmission electron microscopy, and loss of caveolin-1 function. Interleukin-6 and insulin-like growth factor-I, growth and survival factors in multiple myeloma, induce caveolin-1 phosphorylation, which is abrogated by pre-treatment with beta-cyclodextrin. Importantly, inhibition of caveolin-1 phosphorylation blocks both interleukin-6-induced protein complex formation with caveolin-1 and downstream activation of the phosphatidylinositol 3-kinase/Akt-1 pathway. beta-Cyclodextrin also blocks insulin-like growth factor-I-induced tyrosine phosphorylation of insulin-responsive substrate-1 and downstream activation of the phosphatidylinositol 3-kinase/Akt-1 pathway. Therefore, cholesterol depletion by beta-cyclodextrin abrogates both interleukin-6- and insulin-like growth factor-I-triggered multiple myeloma cell survival via negative regulation of caveolin-1. Taken together, this study identifies caveolin-1 and other structural membrane components as potential new therapeutic targets in multiple myeloma.

  10. Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion, Extranodal Extension, and Lower Disease-Free Survival in Thai Breast Cancer Patients.

    Science.gov (United States)

    Sa-Nguanraksa, Doonyapat; Suntiparpluacha, Monthira; Kulprom, Anchalee; Kummalue, Tanawan; Chuangsuwanich, Tuenjai; Avirutnan, Panissadee; O-Charoenrat, Pornchai

    2016-01-01

    Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.

  11. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

    2012-01-01

    Interleukin-6 (IL-6) is a pleiotropic immunomodulatory cytokine produced by various types of cells, including melanoma cells. IL-6 plays a major role in the pathogenesis and development of malignancies. It promotes tumour growth by inhibition of apoptosis and induces tumour angiogenesis. IL-6...... is deregulated in many types of cancers, and increased serum concentration of IL-6 has been correlated with a worse prognosis in patients with different cancers, including melanoma. Several serum cytokines including IL-6 play an important role in the development and progression of melanoma; however, the specific...... biological functions of IL-6 in progression of melanoma are unknown. In this review, we present studies on cell cultures and mouse models and summarize published clinical studies on IL-6 and melanoma....

  12. Serum levels of interleukin-6, tumor necrosis factor-alpha and interferon-gama in infants with and without dengue Níveis séricos de interleucina-6, fator de necrose tumoral-alfa e interferon-gama em crianças menores de um ano com e sem dengue

    Directory of Open Access Journals (Sweden)

    Berta Nelly Restrepo

    2008-02-01

    Full Text Available This study compared the serum levels of IL-6, TNF-alpha and IFN-gamma, in children under 1 year of age with and without dengue. Sera were collected from a total of 41 children living in the Department of Antioquia, Colombia (27 patients with dengue and 14 controls. The results showed higher cytokine levels in children with dengue than without dengue, with statistically significant differences for IL-6 and IFN-gamma. No statistically significant differences were found between clinical forms, although IL-6 and IFN-gamma levels were higher in dengue fever cases than in dengue hemorrhagic fever cases. On the other hand, TNF-alpha levels were higher in dengue hemorrhagic fever than in dengue fever. The levels of IL-6 and TNF-alpha were higher in secondary infection than in primary infection, although IFN-gamma levels were higher in primary infection. These results suggest that IL-6, TNF-alpha and IFN-gamma are involved in dengue infection independently of the clinical form.Este estudo comparou os níveis séricos de IL-6, TNF-alfa e IFN-gama, em crianças menores de um ano com e sem dengue. Os soros foram coletados de um total de 41 crianças residentes no Departamento de Antioquia, Colômbia (27 pacientes com dengue e 14 controles. Os resultados mostraram níveis de citoquinas mais elevadas em crianças com dengue do que naquelas sem dengue, com diferenças estatisticamente significativas para IL-6 and IFN-gama. Não houve diferenças estatisticamente significativas entre formas clínicas, embora os níveis de IL-6 e IFN-gama estivessem mais elevados nos casos de febre do dengue que nos casos de febre hemorrágica do dengue. Por outro lado, os níveis de TNF-alfa estavam mais elevados na febre hemorrágica do dengue que na febre do dengue. Os níveis de IL-6 and TNF-alfa estavam mais elevados em infecções secundárias que em infecções primarias, embora os níveis de IFN-gama estivessem mais elevados em infecções primárias. Estes resultados

  13. Human immunodeficiency virus-1 negative factor protein promotes human herpesvirus-8 viral interleukin-6-induced angiogenesis: role of glycogen synthase kinase-3β/ β-catenin signaling pathway

    Institute of Scientific and Technical Information of China (English)

    姚水洪

    2014-01-01

    Objective To explore the role of glycogen synthase kinase(GSK)-3β/β-catenin signaling pathway on human immunodeficiency virus-1(HIV-1)negative factor(Nef)protein promoting of human herpesvirus-8(HHV-8)viral interleukin-6(v IL-6)induced angiogenesis.Methods GSK-3βmutant plasmid GSK-3β-S9A,dominant-negative(DN)form GSK-3β-DN and the control vector pc DNA3.1+were transfected into endothelial cells which

  14. CHANGES OF INTERLEUKIN-6 AND RELATED FACTORS AS WELL AS GASTRIC INTRAMUCOSAL Ph DURING COLORECTAL AND ORTHOPAEDIC SURGICAL PROCEDURES

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the changes of perioperative serum levels of interleukin-6 ( IL-6), C-reactive protein (CRP), and cortisol, as well as gastric intramucosal pH (pHi) and plasma lactate, aiming to compare systemic changes and tissue perfusion during colorectal and orthopaedic surgical procedures. Methods Twenty patients were randomly assigned to two groups, 10 cases of operation on vertebral canal, 10 cases of colorectal radical operation. Venous blood was drawn at 1 day before operation, 2, 4, and 6 hours following skin incision, and 1 day after operation, in order to measure serum IL-6, CRP, and cortisol, pHi and plasma lactate were also measured at the same time points. Results Serum concentrations of IL-6 and cortisol increased gradually following operation, reaching the peak value at 6 hours from the beginning of operation. CRP was not detectable until the first day after operation. Peak concentration of IL-6 had positive relationship with CRP. These variables changed more significantly in colorectal group than that in orthopaedic group (P < 0. 05). pHi decreased gradually, reaching the lowest level at 4 hours from the beginning of operation, and to more extent in colorectal group than that in orthopaedic group ( P < 0. 05 ).Conclusion IL-6 may reflect tissue damage more sensitively than CRP. Colorectal surgery might induce systemic disorder to more extent, in terms of immuno-endocrinal aspect as well as tissue perfusion, reflected with pHi.

  15. Macrophage colony-stimulating factor augments beta-amyloid-induced interleukin-1, interleukin-6, and nitric oxide production by microglial cells.

    Science.gov (United States)

    Murphy, G M; Yang, L; Cordell, B

    1998-08-14

    In Alzheimer's disease (AD), a chronic cerebral inflammatory state is thought to lead to neuronal injury. Microglia, intrinsic cerebral immune effector cells, are likely to be key in the pathophysiology of this inflammatory state. We showed that macrophage colony-stimulating factor, a microglial activator found at increased levels in the central nervous system in AD, dramatically augments beta-amyloid peptide (betaAP)-induced microglial production of interleukin-1, interleukin-6, and nitric oxide. In contrast, granulocyte macrophage colony-stimulating factor, another hematopoietic cytokine found in the AD brain, did not augment betaAP-induced microglial secretory activity. These results indicate that increased macrophage colony-stimulating factor levels in AD could magnify betaAP-induced microglial inflammatory cytokine and nitric oxide production, which in turn could intensify the cerebral inflammatory state by activating astrocytes and additional microglia, as well as directly injuring neurons.

  16. [A case of bladder cancer producing granulocyte colony-stimulating factor and interleukin-6 causing respiratory failure treated with neoadjuvant systemic chemotherapy along with sivelestat].

    Science.gov (United States)

    Matsuzaki, Kyosuke; Okumi, Masayoshi; Kishimoto, Nozomu; Yazawa, Koji; Miyagawa, Yasushi; Uchida, Kinya; Nonomura, Norio

    2013-07-01

    A 67-year-old man visited an urological clinic with a chief complaint of urination pain. Cystourethroscopy and magnetic resonance imaging (MRI) examination revealed a bladder tumor (cT3bN0M0). Marked leukocytosis and respiratory distress with pleural effusion appeared. Pulse steroid therapy improved the general condition partially. The patient was sent to our hospital for further examination. Serum granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were high and the pathological findings of bladder tumor obtained by transurethral resection (TUR) revealed an urothelial carcinoma that produced G-CSF and IL-6. Neoadjuvant systemic chemotherapy was performed along with use of steroid and sivelestat, which ameliorated the respiratory distress. After three courses of systemic chemotherapy, serum G-CSF and IL-6 normalized and cystoprostatectomy was performed. The patient has been in good health at 20 months after the surgery with no evidence of recurrence.

  17. Staphylococcus aureus protein A binding to osteoblast tumour necrosis factor receptor 1 results in activation of nuclear factor kappa B and release of interleukin-6 in bone infection.

    Science.gov (United States)

    Claro, Tânia; Widaa, Amro; McDonnell, Cormac; Foster, Timothy J; O'Brien, Fergal J; Kerrigan, Steven W

    2013-01-01

    Staphylococcus aureus is the major pathogen among the staphylococci and the most common cause of bone infections. These infections are mainly characterized by bone destruction and inflammation, and are often debilitating and very difficult to treat. Previously we demonstrated that S. aureus protein A (SpA) can bind to osteoblasts, which results in inhibition of osteoblast proliferation and mineralization, apoptosis, and activation of osteoclasts. In this study we used small interfering RNA (siRNA) to demonstrate that osteoblast tumour necrosis factor receptor-1 (TNFR-1) is responsible for the recognition of and binding to SpA. TNFR-1 binding to SpA results in the activation of nuclear factor kappa B (NFκB). In turn, NFκB translocates to the nucleus of the osteoblast, which leads to release of interleukin 6 (IL-6). Silencing TNFR-1 in osteoblasts or disruption of the spa gene in S. aureus prevented both NFκB activation and IL-6 release. As well as playing a key role in proinflammatory reactions, IL-6 is also an important osteotropic factor. Release of IL-6 from osteoblasts results in the activation of the bone-resorbing cells, the osteoclasts. Consistent with our results described above, both silencing TNFR-1 in osteoblasts and disruption of spa in S. aureus prevented osteoclast activation. These studies are the first to demonstrate the importance of the TNFR-1-SpA interaction in bone infection, and may help explain the mechanism through which osteoclasts become overactivated, leading to bone destruction. Anti-inflammatory drug therapy could be used either alone or in conjunction with antibiotics to treat osteomyelitis or for prophylaxis in high-risk patients.

  18. Tumor necrosis factor- α and interleukin-6: potential interorgan inflammatory mediators contributing to destructive periodontal disease in obesity or metabolic syndrome.

    Science.gov (United States)

    Khosravi, Roozbeh; Ka, Khady; Huang, Ting; Khalili, Saeed; Nguyen, Bich Hong; Nicolau, Belinda; Tran, Simon D

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Roozbeh Khosravi

    2013-01-01

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

  20. Persistent Arthralgia Induced by Chikungunya Virus Infection is Associated with Interleukin-6 and Granulocyte Macrophage Colony-Stimulating Factor

    Science.gov (United States)

    Chow, Angela; Her, Zhisheng; Ong, Edward K. S.; Chen, Jin-miao; Dimatatac, Frederico; Kwek, Dyan J. C.; Barkham, Timothy; Yang, Henry; Rénia, Laurent; Leo, Yee-Sin

    2011-01-01

    Background. Chikungunya virus (CHIKV) infection induces arthralgia. The involvement of inflammatory cytokines and chemokines has been suggested, but very little is known about their secretion profile in CHIKV-infected patients. Methods. A case-control longitudinal study was performed that involved 30 adult patients with laboratory-confirmed Chikungunya fever. Their profiles of clinical disease, viral load, and immune mediators were investigated. Results. When patients were segregated into high viral load and low viral load groups during the acute phase, those with high viremia had lymphopenia, lower levels of monocytes, neutrophilia, and signs of inflammation. The high viral load group was also characterized by a higher production of pro-inflammatory cytokines, such as interferon-α and interleukin (IL)–6, during the acute phase. As the disease progressed to the chronic phase, IL-17 became detectable. However, persistent arthralgia was associated with higher levels of IL-6 and granulocyte macrophage colony-stimulating factor, whereas patients who recovered fully had high levels of Eotaxin and hepatocyte growth factor. Conclusions. The level of CHIKV viremia during the acute phase determined specific patterns of pro-inflammatory cytokines, which were associated with disease severity. At the chronic phase, levels of IL-6, and granulocyte macrophage colony-stimulating factor found to be associated with persistent arthralgia provide a possible explanation for the etiology of arthralgia that plagues numerous CHIKV-infected patients. PMID:21288813

  1. Interleukin-6 production by human monocytes stimulated with Cryptococcus neoformans components.

    Science.gov (United States)

    Delfino, D; Cianci, L; Lupis, E; Celeste, A; Petrelli, M L; Curró, F; Cusumano, V; Teti, G

    1997-06-01

    In order to ascertain if Cryptococcus neoformans components can induce interleukin-6 (IL-6) production, we stimulated human whole blood with purified capsular products. Their potencies in stimulating IL-6 release were mannoproteins > galactoxylomannan = glucuronoxylomannan > alpha(1-3)glucan. IL-6 production was tumor necrosis factor alpha independent and required the presence of monocytes and plasma. Since IL-6 can stimulate replication of the human immunodeficiency virus in monocytic cells, these findings may be clinically relevant.

  2. Interleukin-6 Is a Risk Factor for Atrial Fibrillation in Chronic Kidney Disease: Findings from the CRIC Study.

    Directory of Open Access Journals (Sweden)

    Richard L Amdur

    Full Text Available Atrial fibrillation (AF is the most common sustained arrhythmia in patients with chronic kidney disease (CKD. In this study, we examined the association between inflammation and AF in 3,762 adults with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC study. AF was determined at baseline by self-report and electrocardiogram (ECG. Plasma concentrations of interleukin(IL-1, IL-1 Receptor antagonist, IL-6, tumor necrosis factor (TNF-α, transforming growth factor-β, high sensitivity C-Reactive protein, and fibrinogen, measured at baseline. At baseline, 642 subjects had history of AF, but only 44 had AF in ECG recording. During a mean follow-up of 3.7 years, 108 subjects developed new-onset AF. There was no significant association between inflammatory biomarkers and past history of AF. After adjustment for demographic characteristics, comorbid conditions, laboratory values, echocardiographic variables, and medication use, plasma IL-6 level was significantly associated with presence of AF at baseline (Odds ratio [OR], 1.61; 95% confidence interval [CI], 1.21 to 2.14; P = 0.001 and new-onset AF (OR, 1.25; 95% CI, 1.02 to 1.53; P = 0.03. To summarize, plasma IL-6 level is an independent and consistent predictor of AF in patients with CKD.

  3. Microglia-derived interleukin-6 and leukaemia inhibitory factor promote astrocytic differentiation of neural stem/progenitor cells.

    Science.gov (United States)

    Nakanishi, Masaya; Niidome, Tetsuhiro; Matsuda, Satoru; Akaike, Akinori; Kihara, Takeshi; Sugimoto, Hachiro

    2007-02-01

    Neural stem/progenitor cells (NSPCs) proliferate and differentiate depending on their intrinsic properties and local environment. It has been recognized that astrocytes promote neurogenic differentiation of NSPCs, suggesting the importance of cell-cell interactions between glial cells and NSPCs. Recent studies have demonstrated that microglia, one type of glial cells, play an important role in neurogenesis. However, little is known about how activated microglia control the proliferation and differentiation of NSPCs. In this study, we investigated the possibility that microglia-derived soluble factors regulate the behaviour of NSPCs. To this end, NSPCs and microglial cultures were obtained from rat embryonic day 16 subventricular zone (SVZ) and rat postnatal 1 day cortex, respectively, and the conditioned medium from microglia was prepared. Microglial-conditioned medium had no significant effect on the proliferation of NSPCs. In contrast, it increased the percentage of cells positive for a marker of astrocytes, glial fibrillary acidic protein (GFAP) during differentiation. The induction of astrocytic differentiation by microglial-conditioned medium was reduced by the inhibition of the Janus kinase/signal transducer and activation of transcription (JAK/STAT) and mitogen-activated protein kinase (MAPK) pathways. Furthermore, microglia-derived interleukin (IL)-6 and leukaemia inhibitory factor (LIF) were identified as essential molecules for this astrocytic differentiation using neutralizing antibodies and recombinant cytokines. Our results suggest that microglia as well as astrocytes contribute to the integrity of the local environment of NSPCs, and at least IL-6 and LIF released by activated microglia promote astrocytic differentiation of NSPCs via the activation of the JAK/STAT and MAPK pathways.

  4. Detection and significance of serum interleukin-6, tumor necrosis factor-α and interleukin-1β in first-episode schizophrenia patients

    Institute of Scientific and Technical Information of China (English)

    Tao Yan; Chao Cheng; Hui-Xia Wang; Yuan-Yuan Li; Shuai-Bin Zhang

    2015-01-01

    Objective:To detect changes of serum interleukin-6, tumor necrosis factor-α and interleukin-1β in first-episode and different subtypes, and to analyze the correlation between pathological and immune mechanism.Methods:90 first-episode schizophrenia patients admitted to our hospital were enrolled as observation group, and were subdivided into four groups including negative and positive , family type and distributing types. During the same period, 35 physical healthy volunteers were enrolled as control group. Serum interleukin-6, tumor necrosis factor-αand interleukin-1β in both observation group and control group were detected with enzyme-linked immunosorbent (ELISA), correlation between these factors and mental symptoms were analyzed with pearson correlation analysis.Results:The levels of serum IL-6, TNF-αα, IL-1β of the observation group before and after the treatment were significantly higher than those of control group, the level of IL-1β in observation group after treatment was significantly lower than that before the treatment (P<0.05). Before treatment, the level of IL-6 in family type was significantly higher than that in distributing type, the level of TNF-αα in negative type was significantly higher than that in positive type. After treatment the level of TNF-αα was significantly reduced in family type and negative type, the IL-1β was significantly reduced in four subtypes. Pearson correlation analysis showed that TNF-αα lever was positively correlated with symptoms of negative subtype. IL-1β level and PANSS scores, symptoms of both positive and negative types were positively correlated.Conclusion:The levels of IL-6, TNF-αα, IL-1β levels are significantly increases in patients with first-episode schizophrenia, immune activation may be activated and IL-6 level is closely related to the family type of the disease which is genetic influenced, TNF-αα is associated with symptoms of negative type. IL-1β level may be a certain extent

  5. Regulation of expression and role of leukemia inhibitory factor and interleukin-6 in the uterus of early pregnant pigs.

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    Blitek, A; Morawska, E; Ziecik, A J

    2012-09-15

    Cytokines, which are generally involved in the process of inflammation, may also play a critical role in conceptus implantation. We examined: (1) the expression profiles of leukemia inhibitory factor (LIF) and interleukin (IL)-6 mRNA and their protein content in the endometrium of cyclic and pregnant gilts on Days 10 to 18 after estrus; (2) the effect of conceptus-exposed medium on LIF and IL-6 synthesis in the endometrium; (3) the profiles of IL6R and LIFR mRNA expression in pig conceptuses collected on Days 10 to 18 of pregnancy; and (4) the effect of LIF and IL-6 on the attachment and proliferation of porcine trophoblast cells. The expression of LIF mRNA in the endometrium increased between Days 10 and 12 in both cyclic and pregnant gilts, and tended to be higher in Day 12 pregnant animals compared with nonpregnant ones. The LIF protein content in the uterine lumen peaked on Day 12 of pregnancy, and was higher than on Day 12 of the estrous cycle. Endometrial IL-6 mRNA expression was upregulated on Day 12 in pregnant gilts compared with nonpregnant animals. Moreover, a higher content of IL-6 protein was observed in pregnant than in cyclic gilts. The addition of conceptus-exposed medium resulted in up-regulation of LIF and IL6 mRNA expression, and increased IL-6 content in endometrial slices. In conceptuses, increased mRNA expression was detected on Days 10 to 14 for IL6R and on Day 14 for LIFR, when compared with other days studied. LIF and IL-6 stimulated the attachment and proliferation of trophoblast cells in vitro. In summary, LIF and IL-6 are important components of embryo-uterine interactions during early pregnancy in the pig, and may contribute to successful conceptus implantation.

  6. Sputum interleukin-6, tumor necrosis factor-α and Salivary cortisol as new biomarkers of depression in lung cancer patients.

    Science.gov (United States)

    Du, Yi-jie; Zhang, Hong-ying; Li, Bei; Wu, Xiao; Lv, Yu-bao; Jin, Hua-liang; Cao, Yu-xue; Sun, Jing; Luo, Qing-li; Gong, Wei-yi; Liu, Bao-jun; Wu, Jin-feng; Shi, Shen-xun; Dong, Jing-cheng

    2013-12-02

    Depression is common among lung cancer patients. Increasing evidence has suggested that hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines may play a key role in the pathophysiology of depression as well as cancer. This pilot study investigated the efficacy of sputum interleukin (IL)-6, tumor necrosis factor (TNF)-α and salivary cortisol as new markers to support the diagnosis of depression in lung cancer patients. The diurnal rhythms of sputum IL-6, sputum TNF-α and salivary cortisol were measured in lung cancer patients with and without depression as well as depressed controls and healthy controls. The area under the diurnal variation curves (AUC) over the 24h time course and relative diurnal variation (VAR) were calculated. Receiver operating characteristic (ROC) analysis was performed. Patients with co-morbid depression and lung cancer showed highest level of sputum IL-6 AUC, sputum TNF-α AUC and lowest level of cortisol VAR (Pcortisol VAR demonstrated an optimal cutoff point at 77.8% (AUC=0.94; 95% CI, 0.85-0.98), which is associated with a sensitivity of 82.1% and a specificity of 96.0%. Sputum IL-6 AUC demonstrated a sensitivity of 74.4% and a specificity of 92.0% (AUC=0.81; 95% CI, 0.69-0.90). These findings suggested that higher 24h overall levels of sputum IL-6, TNF-α and flattened diurnal salivary cortisol slopes were associated with depression in lung cancer patients. Sputum IL-6 AUC and salivary cortisol VAR performed best as biomarkers in the diagnosis of depression in lung cancer patients.

  7. Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: implications for inflammatory mediated diseases.

    Directory of Open Access Journals (Sweden)

    Gina M Coudriet

    Full Text Available The generation of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β fuel the acute phase response (APR. To maintain body homeostasis, the increase of inflammatory proteins is resolved by acute phase proteins via presently unknown mechanisms. Hepatocyte growth factor (HGF is transcribed in response to IL-6. Since IL-6 production promotes the generation of HGF and induces the APR, we posited that accumulating HGF might be a likely candidate for quelling excess inflammation under non-pathological conditions. We sought to assess the role of HGF and how it influences the regulation of inflammation utilizing a well-defined model of inflammatory activation, lipopolysaccharide (LPS-stimulation of bone marrow derived macrophages (BMM. BMM were isolated from C57BL6 mice and were stimulated with LPS in the presence or absence of HGF. When HGF was present, there was a decrease in production of the pro-inflammatory cytokine IL-6, along with an increase in the anti-inflammatory cytokine IL-10. Altered cytokine production correlated with an increase in phosphorylated GSK3β, increased retention of the phosphorylated NFκB p65 subunit in the cytoplasm, and an enhanced interaction between CBP and phospho-CREB. These changes were a direct result of signaling through the HGF receptor, MET, as effects were reversed in the presence of a selective inhibitor of MET (SU11274 or when using BMM from macrophage-specific conditional MET knockout mice. Combined, these data provide compelling evidence that under normal circumstances, HGF acts to suppress the inflammatory response.

  8. Histologic Chorioamnionitis, Amniotic Fluid Interleukin 6, Krebs von den Lungen 6, and Transforming Growth Factor β for the Development of Neonatal Bronchopulmonary Dysplasia

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    Hisako Matsumura

    2017-03-01

    Full Text Available Background: Chorioamnionitis (CAM is an important risk factor for the development of bronchopulmonary dysplasia (BPD in preterm infants. Objectives: To evaluate the effects of CAM on the development of BPD using interleukin 6 (IL-6, Krebs von den Lungen 6 (KL-6, and transforming growth factor β 1 (TGF-β 1 in the amniotic fluid as markers for inflammation, lung injury, and fibrosis/remodeling, respectively. Methods: Amniotic fluid concentrations of IL-6, KL-6, and TGF-β 1 were measured with enzyme-linked immunosorbent assay or electrochemiluminescence immunoassay. Results: Of the 36 preterm infants, 18 were exposed to histologically confirmed CAM. Of these, 12 were later diagnosed as having BPD. The IL-6, KL-6, and TGF-β 1 levels in the amniotic fluid significantly increased with increasing histologic severity of CAM. Moreover, these markers were higher in the BPD group with histologic CAM than those without. Conclusions: Our study suggests that CAM is likely to induce inflammatory, injury, and remodeling processes in the fetal lung.

  9. Induction of matrix metalloproteinase-1 by tumor necrosis factor-α is mediated by interleukin-6 in cultured fibroblasts of keratoconus.

    Science.gov (United States)

    Du, Genlai; Liu, Chengxing; Li, Xiaona; Chen, Weiyi; He, Rui; Wang, Xiaojun; Feng, Pengfei; Lan, Weiwei

    2016-12-01

    Inflammatory molecules and matrix metalloproteinase (MMPs) have been found over-expressed in the tear film of patients with keratoconus. However, the mechanistic link between inflammatory molecules and MMPs in the pathogenesis of keratoconus remains still elusive. Therefore, we investigated the effect of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on MMP-1 expression and used IL-6 antibody (IL-6 Ab) to examine the role of IL-6 on TNF-α mediated regulation of MMP-1 in fibroblasts of normal cornea and keratoconus. Real-time polymerase chain reaction, Enzyme-linked immunosorbent assay, and Western blot data demonstrated that MMP-1 and IL-6 were expressed in fibroblasts of normal cornea and keratoconus. Levels of MMP-1 and IL-6 were significantly higher in keratoconus than normal cornea. TNF-α treatment led to a significant increase in IL-6 levels. IL-6 treatment induced MMP-1 synthesis in normal cornea and keratoconus. TNF-α increased MMP-1 expression in a dose- and time-dependent manner and this response was completely inhibited by the IL-6 Ab. In conclusion, these results indicate that fibroblasts of keratoconus shows increased levels of IL-6 and MMP-1 gene and protein expression and IL-6 mediates the TNF-α-induced MMP-1 expression.

  10. Aqueous Interleukin-6 Levels Are Superior to Vascular Endothelial Growth Factor in Predicting Therapeutic Response to Bevacizumab in Age-Related Macular Degeneration

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    Kakarla V. Chalam

    2014-01-01

    Full Text Available Objective. To prospectively evaluate the effect of intravitreal bevacizumab on aqueous levels of interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF in patients with exudative age-related macular degeneration (AMD and correlate clinical outcomes with cytokine levels. Methods. 30 eyes of 30 patients with exudative AMD underwent intravitreal injection of bevacizumab three times at monthly intervals. The aqueous samples prior to the 1st injection (baseline and 3rd injection were analyzed for VEGF and IL-6 levels. Subjects were subgrouped based upon change in the central subfield (CSF macular thickness on SD-OCT at 8 weeks. Group 1 included patients (n=14 with a decrease in CSF thickness greater than 10% from the baseline (improved group. Group 2 included patients (n=16 who had a decrease in CSF thickness 10% or less (treatment-resistant. Results. In subgroup analysis, in both groups 1 and 2 patients, compared to aqueous VEGF, aqueous IL-6 levels showed a better correlation with CSF thickness on SD-OCT (r=0.72 and 0.71, resp.. Conclusions. Aqueous IL-6 may be an important marker of treatment response or resistance in wet macular degeneration. Future therapeutic strategies may include targeted treatment against both VEGF and IL-6, in patients who do not respond to anti-VEGF treatment alone.

  11. Expression and cytotoxicity of a human interleukin-6 tumor necrosis factor derivative fusion protein (5'IL6-TNF△) in vitro

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective :To develop an agent that is more active against receptor-bearing target cells without increasing the toxic effect on non-target cells. Methods :By the use of molecular biology techniques,we designed and constructed a fusion protein 5'IL6-TNF△ by connecting the human interleukin-6 (hIL-6) gene and a human tumor necrosis factor α derivative (TNF△) gene througha synthetic linker sequence followed by subsequent expression in E. Coli. Results: In cytotoxicity assay with myeloma cell line U266, the normal type of 5' IL6-TNF△ showed an antitumor activity 3 times higher than that of TNF△;and the antitumor activity of 5'IL6-TNF△ blocked by IL-6Rwas only 1/30 of that of normal type of 5' IL6-TNF△. Meanwhile,the 5'IL6-TNF△ blocked by an ti-TNF antibody did not show any cytotoxicity to U266 cells. In activity assay with L929 cells ,the toxic effect of the fusion protein was found 1/22 of that of TNF△. Conclusion: The 5'IL6-TNF△fusion protein might be a useful cytotoxic agent in cancer treatment.

  12. Effects of confinement on physiological and psychological responses and expression of interleukin 6 and brain derived neurotrophic factor mRNA in primiparous and multiparous weaning sows

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    Mingyue Zhang

    2017-09-01

    Full Text Available Objective The present study aimed to investigate whether the long-lasting, recurrent restricting of sows leads to the physiological and psychological reaction of discomfort. Methods Sows (Large White that had experienced restricting for about 0.5 or 3 years and age-matched sows kept in a group housing system (loose sows were compared. Pupillary light reflex parameters were measured at the weaning stage. Immediately after slaughter, blood samples were taken to measure serum cortisol levels, and the brain was dissected, gene expression in the hippocampus, frontal cortex and hypothalamus was analyzed. Results The serum cortisol levels were higher in the confined sows than in the loose sows. The full maturity, but not the young adolescent, confined sows had longer latency time in the onset of pupil constriction than their loose counterparts. Real-time polymerase chain reaction analyses revealed an increased expression of interleukin 6 mRNA in the hippocampus and decreased expression of brain derived neurotrophic factor mRNA in hippocampus and hypothalamus and to a lesser extent in the frontal cortex of the full maturity confined sows, compared with the full maturity loose sows. Conclusion Taken together, these data indicated that recurrent restricting stress in full maturity sows leads to the physiological and psychological reaction of discomfort.

  13. Effects of confinement on physiological and psychological responses and expression of interleukin 6 and brain derived neurotrophic factor mRNA in primiparous and multiparous weaning sows.

    Science.gov (United States)

    Zhang, Mingyue; Li, Xiang; Li, Jianhong; Sun, Hanqing; Zhang, Xiaohui; Bao, Jun

    2017-09-01

    The present study aimed to investigate whether the long-lasting, recurrent restricting of sows leads to the physiological and psychological reaction of discomfort. Sows (Large White) that had experienced restricting for about 0.5 or 3 years and age-matched sows kept in a group housing system (loose sows) were compared. Pupillary light reflex parameters were measured at the weaning stage. Immediately after slaughter, blood samples were taken to measure serum cortisol levels, and the brain was dissected, gene expression in the hippocampus, frontal cortex and hypothalamus was analyzed. The serum cortisol levels were higher in the confined sows than in the loose sows. The full maturity, but not the young adolescent, confined sows had longer latency time in the onset of pupil constriction than their loose counterparts. Real-time polymerase chain reaction analyses revealed an increased expression of interleukin 6 mRNA in the hippocampus and decreased expression of brain derived neurotrophic factor mRNA in hippocampus and hypothalamus and to a lesser extent in the frontal cortex of the full maturity confined sows, compared with the full maturity loose sows. Taken together, these data indicated that recurrent restricting stress in full maturity sows leads to the physiological and psychological reaction of discomfort.

  14. FISH-OIL INCREASES THE RELEASE OF TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-6, AND HAS NO EFFECT ON THE INCIDENCE OF MULTIPLE ORGAN FAILURE IN RATS WITH PERITONITIS

    NARCIS (Netherlands)

    ROSMAN, C; BUURMAN, WA; DESMET, BJGL; DEJONGE, R; SIETSMA, M; VANSCHILFGAARDE, R; BLEICHRODT, RP

    1993-01-01

    Objective: To find out if fish oil given intraperitoneally would cause a reduction in the release of tumour necrosis factor and interleukin-6 in abdominal exudate and brood (experiment A), and if it reduces the incidence of organ failure in rats with peritonitis (experiment B). Design: Laboratory ex

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  16. Cytokine gene polymorphism (interleukin-1β +3954, Interleukin-6 [-597/-174] and tumor necrosis factor-α -308) in chronic periodontitis with and without type 2 diabetes mellitus.

    Science.gov (United States)

    Sharma, Nitin; Joseph, Rosamma; Arun, R; Chandni, R; Srinivas, K Lekshmy; Banerjee, Moinak

    2014-01-01

    Pro-inflammatory cytokine gene polymorphisms are potential candidates for susceptibility for both type 2 diabetes mellitus (DM) and chronic periodontitis (CHP). This study explored the association of interleukin-1 beta (IL-1 β) +3954, interleukin-6 (IL-6) -597/-174 and tumor necrosis factor-alpha (TNF-α) -308 single nucleotide polymorphisms in CHP with and without type 2 DM in Malayalam speaking subjects of Dravidian ethnicity. This case control study consisted of 51 chronic periodontitis with type 2 diabetes mellitus (CHPDM) and 51 CHP patients as cases and 51 healthy subjects as controls. Polymorphisms were identified by polymerase chain reaction amplification followed by restriction enzyme digestion and gel electrophoresis. IL-1 β (+3954) TT genotype and T allele were significantly associated with CHPDM group when compared with CHP (P = 0.001), whereas CC genotype and allele C was higher in CHP subjects (P = 0.001). For IL-6 (-597) frequency of genotype GA/AA (P = 0.04) and allele A (P = 0.01) was lower in CHPDM group, and for TNF-α -308 the frequency of genotype GA (P = 0.01) and allele A (P = 0.01) was higher in CHP subjects when compared with controls. In Malayalam speaking Dravidian population, IL-6 (-597) genotype GA/AA and allele A appears to be protective for CHP with type 2 DM. Allele C of IL-1 β +3954 and allele A of TNF-α -308 appears to be risk factors for CHP individuals.

  17. Palmitic acid induces production of proinflammatory cytokines interleukin-6, interleukin-1β, and tumor necrosis factor-α via a NF-κB-dependent mechanism in HaCaT keratinocytes.

    Science.gov (United States)

    Zhou, Bing-rong; Zhang, Jia-an; Zhang, Qian; Permatasari, Felicia; Xu, Yang; Wu, Di; Yin, Zhi-qiang; Luo, Dan

    2013-01-01

    To investigate whether palmitic acid can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with palmitic acid at pathophysiologically relevant concentrations. Secretion levels of interleukin-6 (IL-6), tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), NF- κ B nuclear translocation, NF- κ B activation, Stat3 phosphorylation, and peroxisome proliferator-activated receptor alpha (PPAR α) mRNA and protein levels, as well as the cell proliferation ability were measured at the end of the treatment and after 24 hours of recovery. Pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF- κ B) and goat anti-human IL-6 polyclonal neutralizing antibody were used to inhibit NF- κ B activation and IL-6 production, respectively. Our results showed that palmitic acid induced an upregulation of IL-6, TNF- α , IL-1 β secretions, accompanied by NF- κ B nuclear translocation and activation. Moreover, the effect of palmitic acid was accompanied by PPAR α activation and Stat3 phosphorylation. Palmitic acid-induced IL-6, TNF- α , IL-1 β productions were attenuated by NF- κ B inhibitor PDTC. Palmitic acid was administered in amounts able to elicit significant hyperproliferation and can be attenuated by IL-6 blockage. These data demonstrate for the first time that palmitic acid can stimulate IL-6, TNF- α , IL-1 β productions in HaCaT keratinocytes and cell proliferation, thereby potentially contributing to acne inflammation and pilosebaceous duct hyperkeratinization.

  18. (--Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK

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    Osamu Kozawa

    2009-01-01

    Full Text Available We previously showed that the mitogen-activated protein (MAP kinase superfamily, p44/p42 MAP kinase, p38 MAP kinase, and stress-activated protein kinase (SAPK/c-Jun N-terminal (JNK, positively plays a part in the platelet-derived growth factor-BB- (PDGF-BB- stimulated synthesis of interleukin-6 (IL-6, a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells while Akt and p70 S6 kinase negatively regulates the synthesis. In the present study, we investigated whether (--epigallocatechin gallate (EGCG, one of the major green tea flavonoids, affects the synthesis of IL-6 in these cells and the mechanism. EGCG significantly reduced the IL-6 synthesis and IL-6 mRNA expression stimulated by PDGF-BB, EGCG reduced the PDGF-BB-stimulated IL-6 synthesis also in primary-cultured osteoblasts. EGCG had no effect on the levels of osteocalcin and osteoprotegerin in MC3T3-E1 cells. The PDGF-BB-induced autophosphorylation of PDGF receptor β was not suppressed by EGCG. The PDGF-BB-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was not affected by EGCG. On the other hand, EGCG markedly suppressed the PDGF-BB-induced phosphorylation of SAPK/JNK. Finally, the PDGF-BB-induced phosphorylation of Akt and p70 S6 kinase was not affected by EGCG. These results strongly suggest that EGCG inhibits the PDGF-BB-stimulated synthesis of IL-6 via suppression of SAPK/JNK pathway in osteoblasts.

  19. Secretion of interleukin-6 and vascular endothelial growth factor by spindle cell sarcoma complicating Castleman's disease (so-called 'vascular neoplasia').

    Science.gov (United States)

    Kakiuchi, Chihiro; Ishida, Tsuyoshi; Sato, Hitoshi; Katano, Harutaka; Ishiko, Tositaka; Mukai, Hiroyuki; Kogi, Mieko; Kasuga, Naoki; Takeuchi, Kengo; Yamane, Kenichi; Fukayama, Masashi; Mori, Shigeo

    2002-06-01

    So-called 'vascular neoplasia' (VN) is a rare tumour of unknown origin that complicates hyaline vascular type Castleman's disease (CD). This paper reports a case of VN complicating CD of hyaline vascular type, in which neoplastic cells were shown to secrete interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). In this case, VN first occurred in the retroperitoneum of a 60-year-old male. The lesion showed typical morphology, with three distinct areas: (1) a lymph node-like area with regressively transformed lymph follicles showing hyaline vascular changes and with a hypervascular interfollicular region filled with slit-like vascular channels; (2) an area composed of spindle cell sarcoma; and (3) an area showing angiolipomatous hamartoma. A proportion of the cells in the spindle cell area showed severe pleomorphism. Subcutaneous recurrence after 8 months was composed purely of pleomorphic spindle cells. A karyotypic analysis of the recurrent tumour showed 47, XXY with some instability. Supernatant from primary culture contained high levels of IL-6 and VEGF, suggesting high secretion of these cytokines from neoplastic cells. Immunohistochemically, p53 overexpression was identified only in the pleomorphic spindle cells of the primary lesion and metastatic tumour. No features suggestive of vascular origin were shown on immunohistochemical or electron microscopic analysis of the neoplastic cells. Human herpesvirus type 8 was not detected by immunohistochemistry or PCR analysis. High levels of IL-6 and/or VEGF have been reported to play a role in CD. This is the first case report that clarifies the site of such cytokine production, showing the possibility of CD as a paraneoplastic phenomenon.

  20. Changes of interleukin-1β, tumor necrosis factor α and interleukin-6 in brain and plasma after brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    朱涛; 姚智; 袁汉娜; 陆伯刚; 杨树源

    2004-01-01

    Objective: To study the changes of interleukin-1 β (IL-1β), tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) levels in brain and plasma after brain injury and to assess the relationship between the cytokine levels and injury severity in rats. Methods: A total of 51 male Wistar rats, weighing 280-340 g, were anesthetized with chloral hydrate (400 mg/kg body weight) through intraperitoneal injection and fixed on a stereotaxic instrument. Severe brain injury was created in 16 rats (severe injury group) and moderate brain injury in 18 rats (moderate injury group) by a fluid percussion model, and cytokine levels of IL-1β, TNFα and IL-6 were measured with biological assay. And sham operation was made on the other 17 rats (control group). Results: In the control group, the levels of IL-1β, TNFα and IL-6 were hardly detected in the cortex of the rats, but in the ipsilateral cortex of the rats in both injury groups, they increased obviously at 8 hours after injury. The increasing degree of these cytokines had no significant difference between the two injury groups. The levels of IL-6 in the plasma of all the rats increased slightly, whereas the levels of IL-1β and TNFα were undetectable. Conclusions: The increase of IL-1β, TNFα and IL-6 levels is closely related to brain injury. The increased cytokine levels in the central nervous system are not parallel to those in the peripheral blood. It suggests that inflammatory cytokines play important roles in the secondary neural damage after brain injury.

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

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    Lea-Jessica Albrecht

    2016-01-01

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

  2. Keap1 silencing boosts lipopolysaccharide-induced transcription of interleukin 6 via activation of nuclear factor κB in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peng [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Xue, Peng; Dong, Jian [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Peng, Hui [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Clewell, Rebecca [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Wang, Aiping [Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Wang, Yue [Institute for Medical Device Standardization Administration, National Institutes for Food and Drug Control, Beijing (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences (China); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2013-11-01

    Interleukin-6 (IL6) is a multifunctional cytokine that regulates immune and inflammatory responses. Multiple transcription factors, including nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf2), regulate IL6 transcription. Kelch-like ECH-associated protein 1 (Keap1) is a substrate adaptor protein for the Cullin 3-dependent E3 ubiquitin ligase complex, which regulates the degradation of many proteins, including Nrf2 and IκB kinase β (IKKβ). Here, we found that stable knockdown of Keap1 (Keap1-KD) in RAW 264.7 (RAW) mouse macrophages and human monocyte THP-1 cells significantly increased expression of Il6, and Nrf2-target genes, under basal and lipopolysaccharide (LPS, 0.001–0.1 μg/ml)-challenged conditions. However, Nrf2 activation alone, by tert-butylhydroquinone treatment of RAW cells, did not increase expression of Il6. Compared to cells transduced with scrambled non-target negative control shRNA, Keap1-KD RAW cells showed enhanced protein levels of IKKβ and increased expression and phosphorylation of NF-κB p65 under non-stressed and LPS-treated conditions. Because the expression of Il6 in Keap1-KD RAW cells was significantly attenuated by silencing of Ikkβ, but not Nrf2, it appears that stabilized IKKβ is responsible for the enhanced transactivation of Il6 in Keap1-KD cells. This study demonstrated that silencing of Keap1 in macrophages boosts LPS-induced transcription of Il6 via NF-κB activation. Given the importance of IL6 in the inflammatory response, the Keap1–IKKβ–NF-κB pathway may be a novel target for treatment and prevention of inflammation and associated disorders. - Highlights: • Knockdown of Keap1 increases expression of Il6 in macrophages. • Silencing of Keap1 results in protein accumulation of IKKβ and NF-κB p65. • Induction of Il6 resulting from Keap1 silencing is attributed to NF-κB activation.

  3. Interleukin-6 receptor polymorphism is prevalent in HIV-negative Castleman Disease and is associated with increased soluble interleukin-6 receptor levels.

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    Katie Stone

    Full Text Available Multicentric Castleman Disease is largely driven by increased signaling in the pathway for the plasma cell growth factor interleukin-6. We hypothesized that interleukin-6/interleukin-6 receptor/gp130 polymorphisms contribute to increased interleukin-6 and/or other components of the interleukin-6 signaling pathway in HIV-negative Castleman Disease patients. The study group was composed of 58 patients and 50 healthy donors of a similar racial/ethnic profile. Of seven polymorphisms chosen for analysis, we observed an increased frequency between patients and controls of the minor allele of interleukin-6 receptor polymorphism rs4537545, which is in linkage disequilibrium with interleukin-6 receptor polymorphism rs2228145. Further, individuals possessing at least one copy of the minor allele of either polymorphism expressed higher levels of soluble interleukin-6 receptor. These elevated interleukin-6 receptor levels may contribute to increased interleukin-6 activity through the trans-signaling pathway. These data suggest that interleukin-6 receptor polymorphism may be a contributing factor in Castleman Disease, and further research is warranted.

  4. Elevation of tumor necrosis factor-α, interleukin-1β and interleukin-6levels in aortic intima of Chinese Guizhou minipigs with streptozotocin-induced diabetes

    Institute of Scientific and Technical Information of China (English)

    LU Lin; DING Feng-hua; SHEN Jie; CHEN Qiu-jin; LOU Sheng; FANG Dan-hong; SHEN Wei-feng; ZHANG Qi; PU Li-jin; XU Xue-wei; ZHANG Rui-yan; ZHANG Jian-sheng; HU Jian; YANG Zheng-kun; L(U) An-kang

    2007-01-01

    Background Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β) and interleukin-6 (IL-6).Methods Twenty-two male Chinese Guizhou minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ-induced diabetic group (n=12) and control group (n=10). STZ (125 mg/kg) was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet β cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-α level in tissue conditioned medium by Western blot. TNF-α, IL-1β and IL-6 mRNA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction (RT-PCR).Results Significant elevation in serum glucose levels was observed one month and six months after STZ induction (P<0.001) and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet β cells, while in pancreas of diabetic minipigs islet β cells almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Western blot demonstrated

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

    Science.gov (United States)

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

    2013-01-01

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

  6. Novel aspects of cytokine action in porcine uterus--endometrial and myometrial production of estrone (E1) in the presence of interleukin 1beta (IL1beta), interleukin 6 (IL6) and tumor necrosis factor (TNFalpha)--in vitro study.

    Science.gov (United States)

    Franczak, Anita; Wojciechowicz, Bartosz; Kotwica, Genowefa

    2013-01-01

    Interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) increased (P < 0.05) estrone (E1) release from endometrial explants of pregnant pigs on days 10 to 11 after 12 h of tissue incubation in vitro with cytokines and on days 12 to 13 after 6 h of incubation. After 12 h of incubation on days 12 to 13 and 15 to 16 of pregnancy only IL6 increased E1 release. In non-gravid pigs IL1beta, IL6 and TNFalpha increased endometrial E1 release only on days 12 to 13 of the estrous cycle. The cytokines did not affect myometrial E1 release on days 10 to 11 and 15 to 16 ofpregnancy. On days 12 to 13 of pregnancy myometrial release of E1 was markedly increased in response to IL 1beta and IL6. In cyclic pigs only IL6 after 6 h of in vitro incubation increased myometrial E1 release on days 12 to 13 and 15 to 16. Progesterone (P4) increased both endometrial and myometrial release of E1 during the studied days of pregnancy and the estrous cycle, except for endometrial release on days 10 to 11 and 15 to 16 of the estrous cycle after 6 h of in vitro incubation. The results demonstrated that these cytokines may regulate the release of E1 both from the endometrium and myometrium harvested from gravid and non-gravid pigs. The results showed a pivotal role of IL 1beta, IL6 and TNFalpha in the regulation of E1 release in the porcine uterus in vitro.

  7. A Histologically Distinctive Interstitial Pneumonia Induced by Overexpression of the Interleukin 6, Transforming Growth Factor β1, or Platelet-Derived Growth Factor B Gene

    Science.gov (United States)

    Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu

    1995-10-01

    Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

  8. Logic Features Selection in Identification of the Most Important Interactions of Interleukin-6 and Two Important Single Nucleotide Polymorphisms of Its Gene (IL-6-174, IL-6-572 with Some Other Factors in Association with hypertension

    Directory of Open Access Journals (Sweden)

    Hamid Alavi Majd

    2012-10-01

    Full Text Available Introduction: The study aimed to identify important interactions between Interleukin-6 and two single nucleotide polymorphisms of its gene expression (IL-6-174, IL-6-572 with some other factors including gender, age group, BMI, as while as blood concentration of sugar, lipids, and C-reactive protein, in association with hypertension. Methods: In this cross-sectional study, the data of first phase of the "Evaluation of Novel Risk Factors of NCD" project conducted in 2001by the Research Institute for Endocrine Sciences was used. To identify the interactions we used logic Features Selection approach. Analyses were done by logistic regression models using adjusted odds ratio (OR to demonstrate the associations of interest. Results: Based on final selected model on data of 126 men and 208 women with age of 18 or more, significant regression coefficients were reported for individual variables including fasting blood sugar≥126mg/dl (P=0.001, body mass index>25 (P=0.03, and age>40 years of old (P200 mg/dl+ age>40+ interloukin-6 >29+ fasting blood sugar<126mg/dl (P=0.003.Conclusion: Findings suggested that in addition to age, body mass index and fasting blood sugar, having high level of interleukin-6 besides high plasma concentration of total cholesterol in older adults with non diabetic fasting blood sugar can significantly increase hypertension prevalence, applying logic Features Selection approach.

  9. Prediagnosis biomarkers of insulin-like growth factor-1, insulin, and interleukin-6 dysregulation and multiple myeloma risk in the Multiple Myeloma Cohort Consortium

    NARCIS (Netherlands)

    Birmann, Brenda M.; Neuhouser, Marian L.; Rosner, Bernard; Albanes, Demetrius; Buring, Julie E.; Giles, Graham G.; Lan, Qing; Lee, I-Min; Purdue, Mark P.; Rothman, Nathaniel; Severi, Gianluca; Yuan, Jian-Min; Anderson, Kenneth C.; Pollak, Michael; Rifai, Nader; Hartge, Patricia; Landgren, Ola; Lessin, Lawrence; Virtamo, Jarmo; Wallace, Robert B.; Manson, Joann E.; Colditz, Graham A.

    2012-01-01

    Insulin-like growth factor-1 (IGF-1), insulin, and IL-6 are dysregulated in multiple myeloma pathogenesis and may also contribute to multiple myeloma etiology. To examine their etiologic role, we prospectively analyzed concentrations of serologic markers in 493 multiple myeloma cases and 978 control

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

    Science.gov (United States)

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

    2014-11-01

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

  11. Influence of glucoregulation quality on c-reactive protein, interleukin-6 and tumor necrosis factor-α level in patients with diabetes type 1

    Directory of Open Access Journals (Sweden)

    Mitrović Milena

    2011-01-01

    Full Text Available Background/Aim. Results of studies which have proved an increased inflammatory activity in diabetes type 1, have been published over recent years. One of possible mechanisms that are used to explain chronic inflammation in diabetes is the state of hyperglycemia leading to the enhanced synthesis of glycosylation end products (AGEs which activate macrophages, increase the oxidative stress and affect the synthesis of interleukins (IL-1, IL-6, tumor necrosis factor-α (TNF-α and C-reactive protein (CRP. The aim of the study was to determine the inflammatory markers (CRP, IL-6, TNF-α in patients with diabetes type 1 and to establish their correlation with glucoregulation parameters and other cardiovascular risk factors as well as to compare them with the healthy controls. Methods. The study included 76 patients with diabetes type 1 and 30 healthy controls. We determined values of inflammatory markers (CRP, IL-6, TNF-α and glucoregulation parameters (fasting glucose HbA1c. Results. The values of CRP (p = 0.014, IL-6 (p = 0.020 and TNF-α (p = 0.037 were statistically significantly higher in the diabetic patients than in the healthy controls. There was a positive correlation between CRP with postprandial glycemia (p = 0.004; the multivariate regression analysis revealed a statistically significant correlation between CRP and age (p = 0.001, smoking (p = 0.055, fasting glucose (p = 0.021 and triglycerides (p = 0.048 as well as between IL-6 and LDLcholesterol (p = 0,009. No statistically significant correlations were found between glycosilated hemoglobin (HbA1c and the inflammatory markers (CRP, IL-6 and TNF-α. Conclusion. The patients with type 1 diabetes were found to have a low level of inflammatory activity manifested by the increased values of CRP, IL-6 and TNF-α.

  12. The pathogenesis of ovarian hyperstimulation syndrome: in vivo studies investigating the role of interleukin-1beta, interleukin-6, and vascular endothelial growth factor.

    Science.gov (United States)

    Pellicer, A; Albert, C; Mercader, A; Bonilla-Musoles, F; Remohí, J; Simón, C

    1999-03-01

    To evaluate systemic and ovarian changes in levels of interleukin (IL)-1beta, IL-6, and vascular endothelial growth factor (VEGF) in response to hCG administration to determine which may be the potential initiator of vascular effects and to identify the main source of the substance; to evaluate serum and follicular fluid levels of these cytokines as markers of ovarian hyperstimulation syndrome (OHSS), and to compare levels of these cytokines under basal conditions in women with normal ovulation and those with polycystic ovary syndrome (PCOS). Prospective controlled study. In vitro fertilization program at the Instituto Valenciano de Infertilidad, Valencia, Spain. Women undergoing IVF, in whom the first two study objectives were analyzed, and women with normal ovulation and patients with PCOS undergoing retrieval of immature oocytes in natural cycles or cycles stimulated for IUI but cancelled during induction of ovulation, in whom the third study objective was analyzed. Serum was collected before and after hCG administration, and follicular fluid was collected at ovum pick-up. Serum and follicular fluid levels of IL-1beta, IL-6, and VEGF. There was a significant increase in serum VEGF levels after hCG administration in patients who were at risk for OHSS compared with those who were not at risk for OHSS. Significantly lower VEGF levels were found in the follicular fluid of patients who were at risk; this decrease was the only useful marker to discriminate between the two groups. Moreover, both groups had similar cytokine production under basal conditions. An increase in serum E2 occurred coincident with a decrease in IL-1beta, IL-6, and VEGF in patients with PCOS. Vascular endothelial growth factor seems to be the mediator of hCG on the vascular tree. There was an early systemic increase in VEGF that may have significance in the development of OHSS. A decrease in the follicular fluid VEGF concentration is a valid marker to identify women in whom OHSS will develop

  13. Angiopoietin-like protein 2 may mediate the inflammation in murine mastitis through the activation of interleukin-6 and tumour necrosis factor-α.

    Science.gov (United States)

    Wang, Ji-Ying; Xiao, Hong-Bo; Sun, Zhi-Liang; Zhang, Da-Sheng

    2015-08-01

    Mastitis is the inflammation of the mammary gland. Recent research has shown that Angiopoietin-like protein 2 (ANGPTL2) is a key inflammatory mediator. In the present study, we tested whether there is a correlation between increased ANGPTL2 expression and inflammation in response to Staphylococcus aureus in murine mastitis and the mechanisms involved. Thirty mice were divided into two groups: blank control group, challenged group. The entire infused mammary glands were removed to observe the changes of histopathology, myeloperoxidase (MPO) activity, production of tumour necrosis factor-α (TNF-α) and interleukin (IL)-6, and genes expression of ANGPTL2, TNF-α and IL-6. In challenged group, the structure of mammary glands was damaged and the large areas of cell fragments were observed. The MPO activity, IL-6 and TNF-α concentrations, ANGPTL2, IL-6, and TNF-α mRNA levels were significantly elevated in challenged group compared with blank control group. The present findings indicate ANGPTL2 may mediate the inflammation in murine mastitis through the activation of IL-6 and TNF-α.

  14. Prediagnosis biomarkers of insulin-like growth factor-1, insulin, and interleukin-6 dysregulation and multiple myeloma risk in the Multiple Myeloma Cohort Consortium

    Science.gov (United States)

    Neuhouser, Marian L.; Rosner, Bernard; Albanes, Demetrius; Buring, Julie E.; Giles, Graham G.; Lan, Qing; Lee, I-Min; Purdue, Mark P.; Rothman, Nathaniel; Severi, Gianluca; Yuan, Jian-Min; Anderson, Kenneth C.; Pollak, Michael; Rifai, Nader; Hartge, Patricia; Landgren, Ola; Lessin, Lawrence; Virtamo, Jarmo; Wallace, Robert B.; Manson, JoAnn E.; Colditz, Graham A.

    2012-01-01

    Insulin-like growth factor-1 (IGF-1), insulin, and IL-6 are dysregulated in multiple myeloma pathogenesis and may also contribute to multiple myeloma etiology. To examine their etiologic role, we prospectively analyzed concentrations of serologic markers in 493 multiple myeloma cases and 978 controls from 8 cohorts in the Multiple Myeloma Cohort Consortium. We computed odds ratios (ORs) and 95% confidence intervals (CIs) for multiple myeloma per 1-SD increase in biomarker concentration using conditional logistic regression. We examined heterogeneity by time since blood collection (≤ 3, 4- ≤ 6, and > 6 years) in stratified models. Fasting IGF binding protein-1 concentration was associated with multiple myeloma risk within 3 years (OR, 95% CI per 1-SD increase: 2.3, 1.4-3.8, P = .001) and soluble IL-6 receptor level was associated within 6 years after blood draw (OR ≤ 3 years, 95% CI, 1.4, 1.1-1.9, P = .01; OR4- ≤ 6 years, 95% CI, 1.4, 1.1-1.7, P = .002). No biomarker was associated with longer-term multiple myeloma risk (ie, > 6 years). Interactions with time were statistically significant (IGF binding protein-1, P-heterogeneity = .0016; sIL6R, P-heterogeneity = .016). The time-restricted associations probably reflect the bioactivity of tumor and microenvironment cells in transformation from monoclonal gammopathy of undetermined significance or smoldering multiple myeloma to clinically manifest multiple myeloma. PMID:23074271

  15. Intragingival injection of Porphyromonas gingivalis-derived lipopolysaccharide induces a transient increase in gingival tumour necrosis factor-a, but not interleukin-6, in anaesthetised rats

    Institute of Scientific and Technical Information of China (English)

    Hiroko Taguchi; Yuri Aono; Takayuki Kawato; Masatake Asano; Noriyoshi Shimizu; Tadashi Saigusa

    2015-01-01

    This study used in vivo microdialysis to examine the effects of intragingival application of lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (Pg-LPS) on gingival tumour necrosis factor (TNF)-a and interleukin (IL)-6 levels in rats. A microdialysis probe with an injection needle attached to the surface of the dialysis membrane was implanted into the gingiva of the upper incisor. For comparison, the effects of LPS derived fromEscherichia coli (Ec-LPS) on IL-6 and TNF-a levels were also analysed. Pg-LPS (1 mg/1 mL) or Ec-LPS (1 or 6 mg/1 mL) was applied by microsyringe, with gingival dialysates collected every hour. Enzyme-linked immunosorbent assay (ELISA) revealed that gingival dialysates contained approximately 389 pg?mL21 of IL-6 basally; basal TNF-a levels were lower than the detection limit of the ELISA. Pg-LPS failed to alter IL-6 levels but markedly increased TNF-a levels, which remained elevated for 2 h after treatment. Neither IL-6 nor TNF-a were affected by Ec-LPS. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the gingiva expresses Toll-like receptor (TLR) 2 and TLR4 mRNA. Immunohistochemical examination showed that TLR2 and TLR4 are expressed by gingival epithelial cells. The present study provides in vivo evidence that locally applied Pg-LPS, but not Ec-LPS, into the gingiva transiently increases gingival TNF-a without affecting IL-6. The present results suggest that TLR2 but not TLR4 expressed on gingival epithelial cells may mediate the Pg-LPS-induced increase in gingival TNF-a in rats.

  16. Interleukin-6 Detection with a Plasmonic Chip

    Science.gov (United States)

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

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

  17. Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng.

    Science.gov (United States)

    Yousef, Mokhtar I; Hussien, Hend M

    2015-04-01

    Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of solid tumors, while its usage is limited due to its nephrotoxicity. The present study was undertaken to examine the effectiveness of ginseng to ameliorate the renal nephrotoxicity, damage in kidney genomic DNA, tumor necrosis factor-α, interleukin 6, tumor suppressor P53, histological changes and oxidative stress induced by cisplatin in rats. Cisplatin caused renal damage, including DNA fragmentation, upregulates gene expression of tumor suppressor protein p53 and tumor necrosis factor-α and IL-6. Cisplatin increased the levels of kidney TBARS, xanthine oxidase, nitric oxide, serum urea and creatinine. Cisplatin decreased the activities of antioxidant enzymes (GST, GPX, CAT and SOD), ATPase and the levels of GSH. A microscopic examination showed that cisplatin caused kidney damage including vacuolization, severe necrosis and degenerative changes. Ginseng co-treatment with cisplatin reduced its renal damage, oxidative stress, DNA fragmentation and induced DNA repair processes. Also, ginseng diminished p53 activation and improved renal cell apoptosis and nephrotoxicity. It can be concluded that, the protective effects of ginseng against cisplatin induced-renal damage was associated with the attenuation of oxidative stress and the preservation of antioxidant enzymes.

  18. EVALUATION OF INTERLEUKIN-6, LYMPHOTOXIN-α AND TNF-α GENE POLYMORPHISMS IN CHRONIC PERIODONTITIS.

    Directory of Open Access Journals (Sweden)

    Velitchka Dosseva-Panova

    2015-09-01

    Full Text Available Background: Periodontitis is a chronic inflammatory disruption of the periodontal supportive tissues. There are the numerous evidences for his bacterial etiology. Though the occurrence of periodontal bacteria is considered to be the main cause of periodontitis, certain characteristics of the individual immune response may also have influence on the disease development and progression, and on the treatment outcomes. There are some reports that attempt to identify genetic factors associated with periodontitis including polymorphisms of interleukin-1 beta (IL-1β, interleukin-6 (IL-6 and tumor necrosis factor-alpha (TNF-α genes. We were interested from the distribution of several genotypes of the cytokines: interleukin-6 - (G-174C and (G-597A, lymphotoxin- α (A+252G, and tumour necrosis factor-alpha (G-308A in patients with chronic periodontitis. Aim: To investigate the association of chronic periodontitis with certain gene polymorphisms of interleukin-6 (IL-6, Lymphotoxin- α, and tumor necrosis factor-alpha (TNF-α. Material and methods: The study included 30 patients with moderate or severe chronic periodontitis, and 10 persons with healthy periodontium. Total genomic DNA was extracted from the buccal epithelial cells. TNF-A (G-308A, IL-6 (G-174C, IL-6 (G-597A and LT-A (A+252G genes polymorphisms were analyzed by Polymerase chain reaction (PCR. Results: Outcomes showed a large variety in genotype’s distribution in the investigated groups. No important difference was observed in the distribution of IL-6, TNF-α and LT-α genotypes between chronic periodontitis patients and controls in this study be reason of the small studied group. However, a significant difference in the LT-α was observed – a prevalence of the genotype GG in patients with severe periodontitis. In relation with IL-6 (G-597A and IL-6 (G-174C genotyping – in both of them in patients with severe periodontitis was occurred most frequently the genotype GG. In patients with

  19. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

    DEFF Research Database (Denmark)

    Sørensen, Inge Juul; Ostergaard, Mikkel; Nielsen, Hans Jørgen

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated......; and adalimumab, n=3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6-12 weeks for up to 3 years. Patients with co-morbidities (n=4), missing baseline samples (n=3), and adverse events (n=5) were excluded. Patients with SpA had...... compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 µg/l (14-572) vs. 43 (20-184)), and MMP-3 (43 µg/l (9.1-401) vs. 16 (2.5-47), p=0.001), whereas total aggrecan was lower (662 µg/l (223-2,219) vs. 816 (399...

  20. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Hetland, Merete Lund; Sørensen, Inge Juul

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated......; and adalimumab, n=3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6-12 weeks for up to 3 years. Patients with co-morbidities (n=4), missing baseline samples (n=3), and adverse events (n=5) were excluded. Patients with SpA had...... compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 μg/l (14-572) vs. 43 (20-184)), and MMP-3 (43 μg/l (9.1-401) vs. 16 (2.5-47), p≤0.001), whereas total aggrecan was lower (662 μg/l (223-2,219) vs. 816 (399...

  1. Dynamic alterations of the levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β in rat primary motor cortex during transhemispheric functional reorganization after contralateral seventh cervical spinal nerve root transfer following brachial plexus avulsion injuries.

    Science.gov (United States)

    Yang, Ming-Jie; Li, Shuang; Yang, Chen-Song; Wang, Xu-Jia; Chang, Shi-Min; Sun, Gui-Xin

    2017-03-22

    The transfer of a contralateral healthy seventh cervical spinal nerve root (cC7) to the recipient nerve in the injured side is considered a reliable and effective procedure for restoration of the physiological functions of an injured hand after brachial plexus root avulsion injury (BPAI). Growing evidence shows that the transhemispheric cortical reorganization is induced after cC7 nerve transfer surgery. However, little is known about the underlying molecular mechanism. Proinflammatory cytokines reportedly play an important role in the neural plasticity. We hypothesize that proinflammatory cytokines are involved in the transhemispheric functional reorganization after cC7 transfer. In the present study, we investigated the level of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the rat primary motor cortex after cC7 transfer following BPAI by enzyme-linked immunosorbent assay. The results showed that, in the sham group, no statistical significance was observed between the level of TNF-α, IL-6, and IL-1β at each time point after the operation compared with that at day 0, respectively. However, in the unrepaired and repaired groups, the level of TNF-α, IL-6, and IL-1β changed dynamically. The study is the first to provide evidence for the involvement of proinflammatory cytokines in transhemispheric functional reorganization after cC7 transfer following BPAI, which are useful for understanding the underlying mechanism.

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

    Directory of Open Access Journals (Sweden)

    Qianming Chen

    2007-01-01

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

  3. Interleukin 6-preconditioned neural stem cells reduce ischaemic injury in stroke mice.

    Science.gov (United States)

    Sakata, Hiroyuki; Narasimhan, Purnima; Niizuma, Kuniyasu; Maier, Carolina M; Wakai, Takuma; Chan, Pak H

    2012-11-01

    Transplantation of neural stem cells provides a promising therapy for stroke. Its efficacy, however, might be limited because of massive grafted-cell death after transplantation, and its insufficient capability for tissue repair. Interleukin 6 is a pro-inflammatory cytokine involved in the pathogenesis of various neurological disorders. Paradoxically, interleukin 6 promotes a pro-survival signalling pathway through activation of signal transducer and activator of transcription 3. In this study, we investigated whether cellular reprogramming of neural stem cells with interleukin 6 facilitates the effectiveness of cell transplantation therapy in ischaemic stroke. Neural stem cells harvested from the subventricular zone of foetal mice were preconditioned with interleukin 6 in vitro and transplanted into mouse brains 6 h or 7 days after transient middle cerebral artery occlusion. Interleukin 6 preconditioning protected the grafted neural stem cells from ischaemic reperfusion injury through signal transducer and activator of transcription 3-mediated upregulation of manganese superoxide dismutase, a primary mitochondrial antioxidant enzyme. In addition, interleukin 6 preconditioning induced secretion of vascular endothelial growth factor from the neural stem cells through activation of signal transducer and activator of transcription 3, resulting in promotion of angiogenesis in the ischaemic brain. Furthermore, transplantation of interleukin 6-preconditioned neural stem cells significantly attenuated infarct size and improved neurological performance compared with non-preconditioned neural stem cells. This interleukin 6-induced amelioration of ischaemic insults was abolished by transfecting the neural stem cells with signal transducer and activator of transcription 3 small interfering RNA before transplantation. These results indicate that preconditioning with interleukin 6, which reprograms neural stem cells to tolerate oxidative stress after ischaemic reperfusion

  4. Cyclin D-1, interleukin-6, HER-2/neu, transforming growth factor receptor-II and prediction of relapse in women with early stage, hormone receptor-positive breast cancer treated with tamoxifen.

    Science.gov (United States)

    Muss, Hyman B; Bunn, Janice Yanushka; Crocker, Abigail; Plaut, Karen; Koh, James; Heintz, Nick; Rincon, Mercedes; Weaver, Donald L; Tam, Diane; Beatty, Barbara; Kaufman, Peter; Donovan, Michael; Verbel, David; Weiss, Linda

    2007-01-01

    We hypothesized that amplification or overexpression of HER-2 (c-erbB-2), the Ki-67 antigen (Mib1), cyclin D-1 (CD1), interleukin-6 (IL-6), or the transforming growth factor beta II receptor, (TGFbetaRII), would predict relapse in women with early stage, estrogen (ER) and/or progesterone receptor (PR) positive breast cancer treated with tamoxifen. Conditional logistic regression models and a new novel analytic method - support vector machines (SVM) were used to assess the effect of multiple variables on treatment outcome. All patients had stage I-IIIa breast cancer (AJCC version 5). We paired 63 patients who were disease-free on or after tamoxifen with 63 patients who had relapsed (total 126); both disease-free and relapsed patients were matched by duration of tamoxifen therapy and time to recurrence. These 126 patients also served as the training set for SVM analysis and 18 other patients used as a validation set for SVM. In a multivariate analysis, larger tumor size, increasing extent of lymph node involvement, and poorer tumor grade were significant predictors of relapse. When HER-2 or CD1 were added to the model both were borderline significant predictors of relapse. The SVM model, after including all of the clinical and marker variables in the 126 patients as a training set, correctly predicted relapse in 78% of the 18 patient validation samples. In this trial, HER-2 and CD1 proved of borderline significance as predictive factors for recurrence on tamoxifen. An SVM model that included all clinical and biologic variables correctly predicted relapse in >75% of patients.

  5. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Mónica Vázquez-Del Mercado

    2015-01-01

    Full Text Available The main cause of death in rheumatoid arthritis (RA is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP antibody levels with increased carotid intima-media thickness (cIMT in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC were studied. All groups were assessed for atherogenic index of plasma (AIP and cIMT. Anti-CCP, C-reactive protein (CRP, and levels of tumor necrosis factor alpha (TNFα and interleukin-6 (IL-6 were measured by enzyme-linked immunosorbent assay (ELISA. Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P<0.001. Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P<0.01, and lower levels of high density lipoprotein cholesterol (HDL-c (P=0.02. The cIMT correlated with levels of anti-CCP (r=0.513, P=0.001, CRP (r=0.799, P<0.001, TNFα (r=0.642, P=0.001, and IL-6 (r=0.751, P<0.001. In multiple regression analysis, cIMT was associated with CRP (P<0.001 and anti-CCP levels (P=0.03. Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events.

  6. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Science.gov (United States)

    Vázquez-Del Mercado, Mónica; Nuñez-Atahualpa, Lourdes; Figueroa-Sánchez, Mauricio; Gómez-Bañuelos, Eduardo; Rocha-Muñoz, Alberto Daniel; Martín-Márquez, Beatriz Teresita; Martínez-García, Erika Aurora; Macias-Reyes, Héctor; Gamez-Nava, Jorge Ivan; Navarro-Hernandez, Rosa Elena; Nuñez-Atahualpa, María Alejandra; Andrade-Garduño, Javier

    2015-01-01

    The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P < 0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P < 0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P = 0.02). The cIMT correlated with levels of anti-CCP (r = 0.513, P = 0.001), CRP (r = 0.799, P < 0.001), TNFα (r = 0.642, P = 0.001), and IL-6 (r = 0.751, P < 0.001). In multiple regression analysis, cIMT was associated with CRP (P < 0.001) and anti-CCP levels (P = 0.03). Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events. PMID:25821796

  7. Polymorphisms in the tumor necrosis factor alpha and interleukin 1-beta promoters with possible gene regulatory functions increase the risk of preterm birth

    DEFF Research Database (Denmark)

    Hollegaard, Mads Vilhelm; Grove, Jakob; Thorsen, Poul

    2008-01-01

    OBJECTIVE: To investigate the relation between 19 selected single nucleotide polymorphisms in three cytokine genes, tumor necrosis factor alpha (TNFA), interleukin 1-beta (IL1B) and interleukin 6 (IL6) and preterm birth (<37 weeks' gestation). DESIGN: Case-control association study. SAMPLE: A tot...

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

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    Fisman Enrique Z

    2010-10-01

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

  9. Haptoglobin gene polymorphisms and interleukin-6 and -8 levels in patients with sickle cell anemia

    Science.gov (United States)

    Pierrot-Gallo, Bruna Spinella; Vicari, Perla; Matsuda, Sandra Satiko; Adegoke, Samuel Ademola; Mecabo, Grazielle; Figueiredo, Maria Stella

    2015-01-01

    Background Haptoglobin genotypes, and interleukin-6 and -8 participate in the pathophysiology of sickle cell anemia. The expression of cytokines is regulated by genetic mechanisms however the effect of haptoglobin polymorphisms on these cytokines is not fully understood. This study aimed to compare the frequency of haptoglobin genotypes and the interleukin-6 and -8 concentrations in sickle cell anemia patients and controls to investigate the association between haptoglobin genotypes and cytokine levels. Methods Sixty sickle cell anemia patients and 74 healthy individuals were analyzed. Haptoglobin genotypes were determined by multiplex polymerase chain reaction, and the interleukin-6 and -8 levels by enzyme linked immunosorbent assay. The association between haptoglobin genotypes and cytokines was investigated by statistical tests. Results Hp2-1 was the most common genotype in both the cases and controls while Hp1-1 was less frequent among sickle cell anemia patients. Interleukin-6 and -8 levels were higher in patients than controls (p-value 0.05). A similar trend was observed among the controls. Conclusion Although, levels of interleukin-6 and -8 were higher in the sickle cell anemia patients, they appeared not to be related to the haptoglobin genotypes. Further investigations are necessary to identify factors responsible for increased secretion of the interleukin-6 and -8 pro-inflammatory cytokines in patients with sickle cell anemia. PMID:26408368

  10. Haptoglobin gene polymorphisms and interleukin-6 and -8 levels in patients with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Bruna Spinella Pierrot-Gallo

    2015-10-01

    Full Text Available BACKGROUND: Haptoglobin genotypes, and interleukin-6 and -8 participate in the pathophysiology of sickle cell anemia. The expression of cytokines is regulated by genetic mechanisms however the effect of haptoglobin polymorphisms on these cytokines is not fully understood. This study aimed to compare the frequency of haptoglobin genotypes and the interleukin-6 and -8 concentrations in sickle cell anemia patients and controls to investigate the association between haptoglobin genotypes and cytokine levels.METHODS: Sixty sickle cell anemia patients and 74 healthy individuals were analyzed. Haptoglobin genotypes were determined by multiplex polymerase chain reaction, and the interleukin-6 and -8 levels by enzyme linked immunosorbent assay. The association between haptoglobin genotypes and cytokines was investigated by statistical tests.RESULTS:Hp2-1 was the most common genotype in both the cases and controls while Hp1-1 was less frequent among sickle cell anemia patients. Interleukin-6 and -8 levels were higher in patients than controls (p-value 0.05. A similar trend was observed among the controls.CONCLUSION: Although, levels of interleukin-6 and -8 were higher in the sickle cell anemia patients, they appeared not to be related to the haptoglobin genotypes. Further investigations are necessary to identify factors responsible for increased secretion of the interleukin-6 and -8 pro-inflammatory cytokines in patients with sickle cell anemia.

  11. Hypoxemia increases serum interleukin-6 in humans

    DEFF Research Database (Denmark)

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

    1997-01-01

    Serum concentrations of interleukin (IL) 1 beta, IL-1 receptor antagonist (IL-1ra), IL-6, tumor necrosis factor (TNF) alpha, and C-reactive protein (CRP) were determined in ten healthy men at sea level and during four days of altitude hypoxia (4350m above sea level). The mean (SD) arterial blood...... oxygen saturations were 78.6 (7.3)%, 82.4 (4.9)%, and 83.4 (5.3)% in the first, second, and third days at altitude, respectively. A symptom score of acute mountain sickness (AMS) revealed that the subjects had mostly light symptoms of AMS. Mean serum IL-6 increased from 1.36 (1.04) pg x ml(-1) at sea...

  12. The effect of tumor necrosis factor α (TNFα), interleukin 1β (IL1β) and interleukin 6 (IL6) on endometrial PGF2α synthesis, metabolism and release in early-pregnant pigs.

    Science.gov (United States)

    Franczak, A; Zmijewska, A; Kurowicka, B; Wojciechowicz, B; Petroff, B K; Kotwica, G

    2012-01-01

    Cytokines produced by the porcine uterus and embryos may be involved in the regulation of endometrial prostaglandin synthesis, metabolism, and release. We studied the effect of tumor necrosis factor α (TNFα), interleukin 1β (IL1β) and interleukin 6 (IL6) on: 1) endometrial release of prostaglandin F2α (PGF2α), 2) expression of the terminal enzyme of PGF2α synthesis--PGF synthase mRNA (PGFS mRNA), 3) secretion of PGF(2)α metabolite--13,14-dihydro-15-keto PGF2α (PGFM) by the endometrium and 4) presence and activity of endometrial NAD-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). The effects of cytokines were determined on days 10-11 and days 12-13, e.g., before and during maternal recognition of pregnancy, and on days 15-16, e.g., during the peri-implantation period and compared with its effect in cyclic gilts on corresponding days of the estrous cycle. TNFα did not affect endometrial release of PGF2α in pregnant and cyclic pigs. IL1β enhanced endometrial PGF2α release on days 12-13 and 15-16 in pregnant and cyclic pigs, respectively. IL6 increased PGF2α release mainly on days 15-16 of pregnancy. Expression of PGFS mRNA was decreased by IL1β on days 12-13 of pregnancy (P<0.05) and increased in response to IL1β, TNFα and IL6 on 12-13 (P<0.05) and 15-16 (P<0.01) of the estrous cycle. IL1β increased release of PGFM in gravid pigs on days 12-13, 15-16 and in non-gravid pigs 10-11 and 15-16 of the cycle. On days 15-16 of pregnancy TNFα and IL6 increased endometrial secretion of PGFM. We determined that in porcine endometrium NAD-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is present. In gravid pigs, the highest expression of endometrial 15-PGDH occurred during days 12-13 of pregnancy, while in non-gravid pigs during days 10-11 of the estrous cycle. These data provide new evidence that TNFα, IL1β, IL6 are involved in the regulation of endometrial synthesis, release and metabolism of PGF2α to protect CL during early pregnancy

  13. Interleukin-6: a cytokine to forget.

    Science.gov (United States)

    Balschun, D; Wetzel, W; Del Rey, A; Pitossi, F; Schneider, H; Zuschratter, W; Besedovsky, H O

    2004-11-01

    It is known that proinflammatory cytokines such as interleukin-6 (IL-6) are expressed in the central nervous system (CNS) during disease conditions and affect several brain functions including memory and learning. In contrast to these effects observed during pathological conditions, here we describe a physiological function of IL-6 in the "healthy" brain in synaptic plasticity and memory consolidation. During long-term potentiation (LTP) in vitro and in freely moving rats, IL-6 gene expression in the hippocampus was substantially increased. This increase was long lasting, specific to potentiation, and was prevented by inhibition of N-methyl-D-aspartate receptors with (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Blockade of endogenous IL-6 by application of a neutralizing anti-IL-6 antibody 90 min after tetanus caused a remarkable prolongation of LTP. Consistently, blockade of endogenous IL-6, 90 min after hippocampus-dependent spatial alternation learning resulted in a significant improvement of long-term memory. In view of the suggested role of LTP in memory formation, these data implicate IL-6 in the mechanisms controlling the kinetics and amount of information storage.

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

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    Brianne M Bettcher

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

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

    DEFF Research Database (Denmark)

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

    1999-01-01

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

  16. Marked Independent Relationship between Circulating Interleukin-6 Concentrations and Endothelial Activation in Rheumatoid Arthritis

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    Patrick H. Dessein

    2013-01-01

    Full Text Available We examined the potential impact of conventional compared with nonconventional cardiovascular risk factors including interleukin-6 levels on endothelial activation in RA. Circulating soluble E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 concentrations were measured in 217 African patients (112 black and 105 white with RA. In comprehensive confounder adjusted mixed regression models, 5 conventional and 4 nonconventional cardiovascular risk factors were associated (P=0.05 to <0.0001 with endothelial activation. Interleukin-6 was the only risk factor related to each endothelial activation molecule and independently contributed by 18% and significantly more than other risk factors to the variation in overall endothelial activation as estimated by an SD (z score of endothelial activation molecule concentrations. The independent interleukin-6-overall endothelial activation relationships were reproduced in various subgroups. Interleukin-6 concentrations relate consistently, markedly, and to a larger extent than other cardiovascular risk factors to endothelial activation in RA. Assessment of interleukin-6 concentrations may enhance cardiovascular risk stratification in RA.

  17. Interleukin-6 serum levels in patients with Parkinson's disease.

    Science.gov (United States)

    Hofmann, Kerly Wollmeister; Schuh, Artur Francisco Schumacher; Saute, Jonas; Townsend, Raquel; Fricke, Daniele; Leke, Renata; Souza, Diogo O; Portela, Luis Valmor; Chaves, Márcia Lorena Fagundes; Rieder, Carlos R M

    2009-08-01

    Several lines of evidence suggest that neuroimmune mechanisms may be involved in the neurodegenerative process of Parkinson's disease (PD). Interleukin-6 (IL-6) is increased in the nigrostriatal region and in the cerebrospinal fluid of patients with PD. IL-6 serum level was evaluated in PD patients. The effects of levodopa treatment and disease severity on IL-6 were also studied. The IL-6 levels were similar between PD patients (treated and not treated) and controls. However, there was a negative correlation of IL-6 levels and the activities of daily living scale (P < 0.05), indicating that patients with more severe disease have higher levels of this cytokine. No correlation involving levodopa treatment and IL-6 serum level was found. The results suggest that only marginal effects of IL-6 occur on the peripheral immune system, and that the role of IL-6 and others neuroimmune factors needs to be well elucidated on PD.

  18. Helicobacter pylori cytotoxin-associated gene A activates tumor necrosis factor-α and interleukin-6 in gastric epithelial cells through P300/CBP-associated factor-mediated nuclear factor-κB p65 acetylation.

    Science.gov (United States)

    Lin, Qiong; Xu, Hui; Chen, Xintao; Tang, Guorong; Gu, Lan; Wang, Yehong

    2015-10-01

    Helicobacter pylori‑initiated chronic gastritis is characterized by the cytotoxin‑associated gene (Cag) pathogenicity island‑dependent upregulation of pro‑inflammatory cytokines in gastric epithelial cells, which is largely mediated by the activation of nuclear factor (NF)‑κB as a transcription factor. However, the precise regulation of NF‑κB activation, particularly post‑translational modifications in the CagA‑induced inflammatory response, has remained elusive. The present study showed that Helicobacter pylori CagA, an important virulence factor, induced the expression of P300/CBP‑associated factor (PCAF) in gastric epithelial cells. Further study revealed that PCAF was able to physically associate with the NF‑κB p65 sub‑unit and enhance its acetylation. More importantly, PCAF‑induced p65 acetylation was shown to contribute to p65 phosphorylation and further upregulation of tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 in gastric adenocarcinoma cells. In conclusion, the results of the present study indicated that Helicobacter pylori CagA enhanced TNF‑α and IL‑6 in gastric adenocarcinoma cells through PCAF‑mediated NF‑κB p65 sub‑unit acetylation.

  19. Regulation of interleukin-6 secretion in murine pituicytes

    DEFF Research Database (Denmark)

    Thorn, Anders; Tuxen, Mikkel; Moesby, Lise;

    2005-01-01

    Pituicytes, the astrocytic glial cells of the neural lobe, are known to secrete interleukin-6 and nitric oxide upon stimulation with various inflammatory mediators, i.e. interleukin-1beta. Nitric oxide is described to modulate the secretion of interleukin-6 in various cell types. The aim...... dependently but did not induce any detectable nitric oxide release. Co-stimulation with interferon-gamma and interleukin-1beta induced a significant nitric oxide release. In addition interferon-gamma inhibits interleukin-1beta induced interleukin-6 secretion dose dependently. The observed effect of interferon...

  20. Association of interleukin-6 gene polymorphism with angina pectoris.

    Science.gov (United States)

    Amorim, Fernanda Gobbi; Campagnaro, Bianca Prandi; Tonini, Clarissa Loureiro; Norbim, Ana Paula Capua; Louro, Iuri Drummond; Vasquez, Elisardo Corral; Arruda, Jose Airton; Meyrelles, Silvana Santos

    2011-10-01

    In this study, we investigated the role of the -174G>C polymorphism of interleukin-6 (IL-6) as a predisposing factor to angina pectoris. Patients were separated into 2 groups: angina (N = 72) and nonangina (N = 71). There were no statistical differences between groups for all cardiovascular risk factors evaluated. The GG genotype frequency was 18% lower in the angina than in the non-angina group, whereas GC + CC was 18% higher in the angina group (P = .036). The frequency of G allele was 11% lower in the angina than in the nonangina group and C allele was 11% higher in the angina group (P = .043). Patients carrying the C allele showed a 2-fold increased risk for angina pectoris (P = .036). Our study demonstrates a high incidence of the -174G>C polymorphism of the IL-6 gene in patients with angina pectoris compared with those carrying the G allele, reinforcing the contribution of genetic factors to the symptoms of angina pectoris.

  1. Interleukin-6 (IL-6) production by astrocytes: autocrine regulation by IL-6 and the soluble IL-6 receptor.

    Science.gov (United States)

    Van Wagoner, N J; Oh, J W; Repovic, P; Benveniste, E N

    1999-07-01

    In the CNS, astrocytes are a major inducible source of interleukin-6 (IL-6). Although IL-6 has beneficial effects in the CNS because of its neurotrophic properties, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. Many factors have been shown to induce IL-6 expression by astrocytes, particularly the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta). However, the role of IL-6 in its own regulation in astrocytes has not been determined. In this study, we examined the influence of IL-6 alone or in combination with TNF-alpha or IL-1beta on IL-6 expression. IL-6 alone had no effect on IL-6 expression; however, the addition of the soluble IL-6 receptor (sIL-6R) induced IL-6 transcripts. Addition of TNF-alpha or IL-1beta plus IL-6/sIL-6R led to synergistic increases in IL-6 expression. This synergy also occurred in the absence of exogenously added IL-6, attributable to TNF-alpha- or IL-1beta-induced endogenous IL-6 protein production. IL-6 upregulation seen in the presence of TNF-alpha or IL-1beta plus IL-6/sIL-6R was transcriptional, based on nuclear run-on analysis. Experiments were extended to other IL-6 family members to determine their role in IL-6 regulation in astrocytes. Oncostatin M (OSM) induced IL-6 alone and synergized with TNF-alpha for enhanced expression. These results demonstrate that IL-6/sIL-6R and OSM play an important role in the regulation of IL-6 expression within the CNS, particularly in conjunction with the proinflammatory cytokines TNF-alpha and IL-1beta.

  2. Interleukin 6 in intact and injured mouse peripheral nerves.

    Science.gov (United States)

    Reichert, F; Levitzky, R; Rotshenker, S

    1996-03-01

    The multifunctional cytokine interleukin 6 (IL-6) has direct growth, survival and differentiation effects on peripheral and central neurons. Furthermore, it can modulate the production by non-neuronal cells of other cytokines and growth factors, and thereby affect nerve cells indirectly. We have studied IL-6 expression and production in intact and injured peripheral nerves of C57/BL/6NHSD mice, which display the normal rapid progression of Wallerian degeneration. The IL-6 mRNA was detected in nerves degenerating in vitro or in vivo, but not in intact nerves. In vitro- and in vivo-degenerating nerve segments and neuroma nerve segments synthesized and secreted IL-6. The onset of IL-6 production was rapid and prolonged. It was detected as early as 2 h after injury and persisted for the entire period of 21 days tested after the injury. Of the non-neuronal cells that reside in intact and injured nerves, macrophages and fibroblasts were the major contributors to IL-6 production. We also studied IL-6 production in intact and injured nerves of mutant C57BL/6-WLD/OLA/NHSD mice, which display very slow progression of Wallerian degeneration. Injured nerves of C57BL/6-WLD/OLA/NHSD mice produced significantly lower amounts of IL-6 than did rapidly degenerating nerves of C57/BL/6NHSD mice.

  3. Interleukin-6 receptor gene polymorphism modulates interleukin-6 levels and the metabolic syndrome: GBCS-CVD.

    Science.gov (United States)

    Jiang, Chao Qiang; Lam, Tai Hing; Liu, Bin; Lin, Jie Ming; Yue, Xiao Jun; Jin, Ya Li; Cheung, Bernard M Y; Thomas, G Neil

    2010-10-01

    Interleukin-6 (IL-6) is a key pleiotropic cytokine that modulates the inflammatory response. Single-nucleotide polymorphisms (SNPs) within associated genes may contribute to the metabolic syndrome (MES). We examined the role of the IL-6 (rs1524107-C/T) and IL-6 receptor (IL-6R, rs8192284-A/C, Asp358Ala) SNPs in modulating IL-6 levels and the syndrome. A total of 1,979 older Chinese subjects aged 50-92 years from Guangzhou Biobank Cohort Study (GBCS) were recruited. SNPs were detected using Taqman SNP genotyping kits. IL-6 was measured using enzyme-linked immunosorbent assay. The genotype frequencies were 4.9, 33.9, and 61.3% for the IL-6 CC, CT, and TT, and 12.0, 44.9, and 43.1% for the IL-6R CC, AC, and AA, respectively. Both SNPs were in Hardy-Weinberg equilibrium. The IL-6 SNP was not associated with IL-6 levels or the MES, but was dose-dependently associated with fibrinogen levels, P = 0.049. IL-6 levels significantly decreased with increasing proportions of the IL-6R A-allele 9.8 ± 4.9, 9.3 ± 4.8, and 8.4 ± 4.3, respectively, P = 0.001. Conversely, the A-allele was associated with elevated triglyceride, P = 0.009, C-reactive protein, P = 0.047, and potentially with fasting glucose levels, P = 0.077. There was an increasing prevalence of the MES in those carrying the IL-6R CC, AC, and AA genotypes at 18.1, 21.5, 25.2%, respectively, P = 0.010. The SNP was a significant independent predictor of the MES after adjusting for general obesity, age, gender and lifestyle, and socioeconomic parameters, P = 0.023. These data, which are in accord with studies from white populations suggest the IL-6R SNP may play a role in the pathogenesis of the MES possibly through modulating IL-6 levels.

  4. Role of cytokine gene (interferon-γ, transforming growth factor-β1, tumor necrosis factor-α, interleukin-6, and interleukin-10 polymorphisms in the risk of oral precancerous lesions in Taiwanese

    Directory of Open Access Journals (Sweden)

    Han-Jen Hsu

    2014-11-01

    Full Text Available Oral squamous cell carcinoma can be preceded by some benign oral lesions with malignant potential, including leukoplakia, erythroplakia, oral lichen planus, and oral submucous fibrosis. There are different degrees of inflammatory cells infiltration in histopathology. Inflammatory cytokines may play a pathogenic role in the development of oral precancerous lesions (OPCLs. Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. We hypothesized that the risk of OPCLs might be associated with cytokine gene polymorphisms of interferon (IFN-γ, transforming growth factor (TGF-β1, tumor necrosis factor (TNF-α, interleukin (IL-6, and IL-10. In the present study, 42 OPCL patients and 128 controls were analyzed for eight polymorphisms in five different cytokine genes [IFN-γ (+874 T/A, TGF-β1 (codons 10 T/C and 25 G/C, TNF-α (−308 G/A, IL-6 (−174 G/C, and IL-10 (−1082 A/G, –819 T/C, and −592 A/C]. Cytokine genotyping was determined by the polymerase chain reaction sequence-specific primer technique using commercial primers. Allele and genotype data were analyzed for significance of differences between cases and controls using the Chi-square (χ2 test. Two-sided p < 0.05 were considered to be statistically significant. A series of multivariate logistic regression models, adjusted for age, sex, betel quid chewing, alcohol consumption, and smoking, was constructed in order to access the contribution of homozygous or heterozygous variant genotypes of polymorphisms. The TNF-α (−308 polymorphism was significantly associated with OPCLs. There were significant differences in the distribution of AA, GA, and GG genotypes between OPCL patients and controls (p = 0.0004. Patients with the AA or GA genotype had a 3.63-fold increased risk of OPCLs. The TGF-β1 (codon 10 and 25 polymorphism was also significantly associated with OPCLs (p < 0.001. The IL-6 polymorphism was significantly associated with OPCLs

  5. Interleukin-6 production in human subcutaneous abdominal adipose tissue

    DEFF Research Database (Denmark)

    Lyngsø, Dorthe; Simonsen, Lene; Bülow, Jens

    2002-01-01

    The interleukin-6 (IL-6) output from subcutaneous, abdominal adipose tissue was studied in nine healthy subjects before, during and for 3 h after 1 h two-legged bicycle exercise at 60 % maximal oxygen consumption. Seven subjects were studied in control experiments without exercise. The adipose ti...

  6. Interleukin-6 receptor pathways in coronary heart disease

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Science.gov (United States)

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

  9. Interleukin-6 as a Prognostic Biomarker in Ruptured Intracranial Aneurysms.

    Directory of Open Access Journals (Sweden)

    Hung-Wen Kao

    Full Text Available Interleukin-6 (IL-6, a proinflammatory cytokine, was found to surge in the cerebral spinal fluid after aneurysmal subarachnoid hemorrhage (SAH. We hypothesized that the plasma level of IL-6 could be an independent biomarker in predicting clinical outcome of patients with ruptured intracranial aneurysm.We prospectively included 53 consecutive patients treated with platinum coil embolization of the ruptured intracranial aneurysm. Plasma IL-6 levels were measured in the blood samples at the orifices of the aneurysms and from peripheral veins. The outcome measure was the modified Rankin Scale one month after SAH. Multiple logistic regression analyses were used to evaluate the associations between the plasma IL-6 levels and the neurological outcome.Significant risk factors for the poor outcome were old age, low Glasgow Coma Scale (GCS on day 0, high Fisher grades, and high aneurysmal and venous IL-6 levels in univariate analyses. Aneurysmal IL-6 levels showed modest to moderate correlations with GCS on day 0, vasospasm grade and Fisher grade. A strong correlation was found between the aneurysmal and the corresponding venous IL-6 levels (ρ = 0.721; P<0.001. In the multiple logistic regression models, the poor 30-day mRS was significantly associated with high aneurysmal IL-6 level (OR, 17.97; 95% CI, 1.51-214.33; P = 0.022 and marginally associated with high venous IL-6 level (OR, 12.71; 95% CI, 0.90-180.35; P = 0.022 after adjusting for dichotomized age, GCS on day 0, and vasospasm and Fisher grades.The plasma level of IL-6 is an independent prognostic biomarker that could be used to aid in the identification of patients at high-risk of poor neurological outcome after rupture of the intracranial aneurysm.

  10. Muscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund; Steensberg, Adam; Keller, Pernille

    2003-01-01

    Interleukin-6 (IL-6) is produced locally in working skeletal muscle and can account for the exercise-induced increase in plasma IL-6. The transcription rate for IL-6 in muscle nuclei isolated from muscle biopsies during exercise is very high and is enhanced further when muscle glycogen content is...... produced during exercise probably inhibits TNF-alpha-induced insulin resistance in peripheral tissues. Hence, IL-6 produced by skeletal muscle during contraction may play an important role in the beneficial health effects of exercise...

  11. Serum levels of interleukin-6 are not dependent on the kidney function

    Directory of Open Access Journals (Sweden)

    L. Nässberger

    1992-01-01

    Full Text Available Interleukin-6, also named B-cell stimulatory factor, is a glycoprotein with a molecular weight of 26 kDa. Increased serum levels of interleukin-6 (IL-6 are found in several disease conditions. We investigated the importance of a deteriorated kidney function upon IL-6 serum concentrations. No relation was found between serum levels of IL-6 and s-creatinine, r = 0.004. On the other hand, the serum concentration of complement protein factor D and soluble IL-2 receptor showed a good correlation to s-creatinine, r = 0.92 and 0.79, respectively. In conclusion, serum levels of IL-6 are not dependent upon a reduced kidney function.

  12. Regulatory roles of tumor necrosis factor alpha-induced proteins (TNFAIPs) 3 and 9 in arthritis.

    Science.gov (United States)

    Matsumoto, Isao; Inoue, Asuka; Takai, Chinatsu; Umeda, Naoto; Tanaka, Yuki; Kurashima, Yuko; Sumida, Takayuki

    2014-07-01

    Tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) have proved to be important in rheumatoid arthritis (RA) because the outcome of RA has greatly improved with the recent availability of biologics targeting them. It is well accepted that these cytokines are involved in the activation of the nuclear factor-κB (NF-κB) signaling pathway, but our understanding of the dependency of these pro-inflammatory cytokines and the link between them in RA is currently limited. Recently, we and others proved the importance of TNFα-induced protein (TNFAIP), due to the spontaneous development of arthritis in deficient animals that are dependent on IL-6. To date, nine TNFAIPs have been identified, and TNFAIP3 and TNFAIP9 were found to be clearly associated with mouse and human arthritis. In this review, we compare and discuss recent TNFAIP topics, especially focusing on TNFAIP3 and TNFAIP9 in autoimmune arthritis in mice and humans.

  13. Serum tumor necrosis factor α and interleukin-6levels in patients with primary aldosteronism%原发性醛固酮增多症患者的血清肿瘤坏死因子α和白细胞介素6水平

    Institute of Scientific and Technical Information of China (English)

    李娟; 李红建; 王红梅; 罗文利; 李涛; 周克明; 李南方

    2011-01-01

    Objective To investigate the levels of tumor necrosis factor alpha (TNF-a) and interleukin-6 (IL-6) in patients with primary aldosteronism (PA) and analyze its association with the renin-angiotensin-aldosterone system. Methods One hundred sixty patients (including 93 PA patients and 67 EH patients) were recruited from hypertension department of People's Hospital of Xinjiang Uygur Autonomous Region. The concentration of TNF-a and IL-6 were measured with radioimmunoassay, and the concentration of high-sensitivity C-reactive protein (hsCRP) were measured with immunoturbidimetry. Results Compared with EH patients, PA patients had lower serum total cholesterol concentration (P0. 05). IL-6 presented a remarkable correlation with serum aldosterone levels (r=-0. 183, P<0. 01) and aldosterone/plasma renin activity ratio (ARR) (r=-0. 331, P<0. 01) in all patients. Conclusion The present study shows that serum IL-6 levels are lower in patients with PA than in patients with EH. There is a significant negative association between IL-6 and serum aldosterone, ARR in all patients.%目的 观察原发性醛固酮增多症(原醛)患者中血清肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的水平,并分析其与肾素血管紧张素醛固酮系统的相关性.方法 收集新疆维吾尔自治区人民医院高血压科的原发性高血压(EH)患者67例作为对照组,原醛患者93例为病例组,采用放射免疫法检测两组患者TNF-α和白细胞介素6(IL-6)的水平,采用免疫比浊法检测血清高敏C反应蛋白(hsCRP)的浓度,比较两组间TNF-α、IL-6和hs-CRP的水平差异.结果 原醛组患者总胆固醇水平较EH组患者低(P<0.01),而收缩压较EH组患者高(P<0.01);协方差校正总胆固醇和收缩压后,原醛组患者的IL-6水平[(0.18±0.05)比(0.24±0.05)μg/L,P<0.01]和hsCRP浓度ln100 hsCRP(3.79±1.3)比(4.39±0.94) mg/L,P<0.01]均较EH组患者低,而两组间TNF-a的水平无统计学差异;Pearson相关分

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

    Science.gov (United States)

    Penkowa, Milena; Camats, Jordi; Hadberg, Hanne; Quintana, Albert; Rojas, Santiago; Giralt, Mercedes; Molinero, Amalia; Campbell, Iain L; Hidalgo, Juan

    2003-08-15

    6-aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray matter astrocytes mainly in the brainstem. We have examined the role of interleukin-6 (IL-6) in this degenerative process by using transgenic mice with astrocyte-targeted IL-6 expression (GFAP-IL6 mice). This study demonstrates that transgenic IL-6 expression significantly increases the 6-AN-induced inflammatory response of reactive astrocytes, microglia/macrophages, and lymphocytes in the brainstem. Also, IL-6 induced significant increases in proinflammatory cytokines IL-1, IL-12, and tumor necrosis factor-alpha as well as growth factors basic fibroblast growth factor (bFGF), transforming growth factor-beta, neurotrophin-3, angiopoietin, vascular endothelial growth factor, and the receptor for bFGF. In accordance, angiogenesis was increased in GFAP-IL6 mice relative to controls after 6-AN. Moreover, oxidative stress and apoptotic cell death were significantly reduced by transgenic IL-6 expression. IL-6 is also a major inducer in the CNS of metallothionein I and II (MT-I+II), which were significantly increased in the GFAP-IL6 mice. MT-I+II are antioxidants and neuroregenerative factors in the CNS, so increased MT-I+II levels in GFAP-IL6 mice could contribute to the reduction of oxidative stress and cell death in these mice.

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

    Science.gov (United States)

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

    1996-01-01

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

  16. Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus infection.

    Science.gov (United States)

    Yee, L J; Im, K; Borg, B; Yang, H; Liang, T J

    2009-06-01

    Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-alpha-2a is successful in eradicating virus from only 30 to 80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained viral response (SVR) to the therapy for chronic HCV infection. We observed the IL-6 T-T-G-G-G-G-C-A-G-A haplotype to be associated with a lower risk of achieving SVR among Caucasian Americans (CAs) ((relative risk) RR=0.80; 95% CI: 0.66-0.98; P=0.0261). Using a sliding window approach, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was associated with a reduced chance of SVR (RR=0.79; 95% CI: 0.66-0.94; P=0.0081), as was the rs1800796-(G)-rs1800795-(G)-rs2069830-(C) haplotype (RR=0.78; 95% CI: 0.66-0.94; P=0.0065) among CAs. Overall, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was independently associated with a reduced chance of SVR (RR=0.78; 95% CI: 0.62-1.0; P=0.0489) after adjustment for potential confounding factors. Our findings further illustrate the complexity of IL-6 genetic regulation and the potential importance of haplotypes on IL-6 expression. Our findings provide additional support for the potential importance of genetic variation in the IL-6 gene and the response to HCV therapy.

  17. Associations between plasma insulin-like growth factor-I and the markers of inflammation interleukin 6, C-reactive protein and YKL-40 in an elderly background population

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Raymond, Ilan; Hildebrandt, Per

    2010-01-01

    The objective of the present study was to test the hypothesis that circulating levels of insulin-like growth factor-I (IGF-I) are inversely associated with inflammatory processes in an elderly background population....

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  19. Cytokine gene polymorphism (interleukin-1β +3954, Interleukin-6 [−597/−174] and tumor necrosis factor-α −308 in chronic periodontitis with and without type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Nitin Sharma

    2014-01-01

    Conclusions: In Malayalam speaking Dravidian population, IL-6 (−597 genotype GA/AA and allele A appears to be protective for CHP with type 2 DM. Allele C of IL-1 β +3954 and allele A of TNF-α −308 appears to be risk factors for CHP individuals.

  20. DYNAMIC EXPRESSION OF PLASMA TUMOR NECROSIS FACTOR-α、INTERLEUKIN-6 AND NUCLEAR FACTOR-κB IN ACUTE ABDOMEN PATIENTS COMBINED WITH SYSTEMIC INFLAMMATORY RESPONSE SYNDROME%急腹症伴SIRS患者血浆细胞因子TNF-α、IL-6及NF-κB的动态变化

    Institute of Scientific and Technical Information of China (English)

    朱世纯; 杜建华; 李倩

    2010-01-01

    目的 检测急腹症伴发全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)患者血浆细胞因子肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)及核因子κB(nuclear factor-κB ,NF-κB)水平的动态变化,并探讨与SIRS的关系.方法 81例急腹症伴SIRS患者于入院当日(0d)及入院后1、3、7d分别采集空腹外周静脉血,用酶联免疫吸附法测定TNF-α、IL-6及NF-κB的血浆浓度,另选30例健康成年人做为对照组.分别对NF-κB活性与TNF-α及IL-6水平进行相关统计学分析.结果 81例急腹症患者血浆各时间点TNF-α、IL-6及NF-κB水平均较对照组显著增高,差异有统计学意义(P<0.05).NF-κB活性增高与TNF-α及IL-6血浆浓度增高呈明显正相关(P<0.05).结论 急腹症伴SIRS时,TNF-α、IL-6及NF-κB表达增多.TNF-α及IL-6血浆浓度与NF-κB活性呈正相关.

  1. The effect of interleukin-1β, interleukin-6, and tumor necrosis factor-α on estradiol-17β release in the myometrium: the in vitro study on the pig model.

    Science.gov (United States)

    Franczak, A; Wojciechowicz, B; Kolakowska, J; Kotwica, G

    2014-01-15

    Estradiol-17β (E2) is a potent regulator of early pregnancy and the estrous cycle in pigs. Production of E2 occurs in the porcine myometrium, but the factors involved in its regulation are unknown. In this in vitro study, it was investigated whether interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α affect the release of E2 from the porcine myometrium on Days 10 to 11, 12 to 13, and 15 to 16 of pregnancy and the estrous cycle. The expression of the cytochrome P450 family 19 (CYP19) gene and the presence of the aromatase cytochrome P450 protein in the myometrium confirmed the ability of the tissue to produce E2. In gravid pigs, the expression of IL1RI mRNA and IL6R mRNA was markedly increased on Days 15 to 16 of gestation, whereas TNFRI mRNA was increased on Days 10 to 11 of gestation. In cyclic pigs, the expression of myometrial IL1RI mRNA did not differ among the studied days, although the expression of IL6R and TNFRI mRNAs was increased on Days 15 to 16. In gravid pigs, IL-1β, IL-6, and TNF-α increased myometrial E2 secretion on Days 15 to 16 but did not affect E2 release on Days 10 to 11 and 12 to 13 of pregnancy. In cyclic pigs, IL-1β, IL-6, and TNF-α did not increase myometrial E2 release. In conclusion, IL-1β, IL-6, and TNF-α affected myometrial E2 release in a manner that is dependent on the physiologic status of the female. The porcine myometrium expresses IL1RI, IL6R, and TNFRI genes and is the target tissue for IL-1β, IL-6, and TNF-α. In gravid pigs, IL-1β, IL-6, and TNF-α may increase myometrial release of E2 in vitro specifically on Days 15 to 16 of pregnancy. These findings may be of interest to researchers using pigs as an animal model for fetal programming.

  2. Penetrability of interleukin-1β and its effect on the concentration of tumor necrosis factor-α and interleukin-6 in the aqueous humor of rabbits treated with interleukin-1β

    Institute of Scientific and Technical Information of China (English)

    PENG Xiao-yan; CHEN Feng-hua; WANG Ning-li; MA Jian-min; Ping-yu Lee; LIU Ke-gao; Steven M Podos

    2009-01-01

    Background Interleukin (IL)-1β may effectively decrease introcular pressure (IOP) when administered by subconjunctival injection in normal rabbit. However, IL-1β is a large molecular agent and an inflammation factor. The aim of this study was to evaluate the penetrability of IL-1β, and the concentrations of both tumor necrosis factor (TNF)-α and IL-6 in the aqueous humor of normal rabbits treated with IL-1β.Methods A total of 170 rabbits were used in the study and were assigned to several different treatment groups as follows: 125 of the rabbits were assigned to two groups. In one group, 33 rabbits were injected subconjunctivally with IL-1β and 39 were injected with saline alone. In the other group, 27 rabbits were given eye drops containing IL-1β (400 ng/ml) and 26 were given saline alone. Aqueous humor (AH) was drawn and the concentration of IL-1β within the fluid measured. The IOP was measured in another six rabbits after administration of eye drops containing IL-1β (400 ng/ml). A further 20 rabbits were assigned to 3 groups as follows: eight untreated normal controls; six injected subconjunctivally with IL-1β; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of TNF-α in the fluid was measured. Another 19 rabbits were assigned to 3 groups as follows: seven untreated normal controls; and six injected subconjunctivally with IL-1β; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of IL-6 in the fluid measured. Measurement of cytokine concentration was by radio-immunoassay in all cases.Results The IL-1β concentration in the AH was higher in those animals in which it had been administered subconjunctivally (P 0.05). The administration of IL-1β in the form of eye drops had little effect upon lOP reduction. Lower TNF-α concentrations were seen in the AH after the subconjunctival administration of IL-1β, but the concentration of IL-6 was the same as in the normal controls

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

    OpenAIRE

    2014-01-01

    Interleukin-6 (IL-6) is a key pro-inflammatory cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals. The Chinese Hui is one of the largest ethnic minorities, little is known about the distribution of IL-6 genetic variations and their effects on serum levels in Hui population. The aim of the present study is to determine the prevalence of -174G/C (rs1800795), -597G/A (rs1800797), and -634C/G (rs1800796) pol...

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

    DEFF Research Database (Denmark)

    Pedersen, Bente Klarlund

    2012-01-01

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

  5. Nicotinamide downregulates gene expression of interleukin-6, interleukin-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α gene expression in HaCaT keratinocytes after ultraviolet B irradiation.

    Science.gov (United States)

    Monfrecola, G; Gaudiello, F; Cirillo, T; Fabbrocini, G; Balato, A; Lembo, S

    2013-03-01

    Ultraviolet (UV) radiation has profound effects on human skin, causing sunburn, inflammation, cellular-tissue injury, cell death, and skin cancer. Most of these effects are mediated by a number of cytokines produced by keratinocytes. In this study we investigated whether nicotinamide (NCT), the amide form of vitamin B3, might have a protective function in reducing the expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1 and tumour necrosis factor (TNF)-α in UV-irradiated keratinocytes. HaCaT cells were treated with UVB in the presence or absence of NCT, and cytokine mRNA levels were examined by quantitative real-time PCR. NCT significantly downregulated IL-6, IL-10, MCP-1 and TNF-α mRNA expression, whereas it did not exert any significant effect on IL-1β or IL-8 expression. Because of its ability to decrease these cytokine mediators after UV exposure, NCT is a possible therapy to improve or prevent conditions induced or aggravated by UV light.

  6. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors

    DEFF Research Database (Denmark)

    Damgaard, C; Kantarci, A; Holmstrup, P

    2017-01-01

    in both groups, but reduced the generation of ROS in the group of healthy controls, and showed a similar tendency in the group of subjects with LAgP. RvE1 had no impact on the production of intracellular ROS, TNF-α, IL-6, CXCL8 and CCL2 by neutrophils from either group, but tended to reduce the generation...... healthy controls release the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor α (TNF-α), the chemokine (C-X-C motif) ligand 8 (CXCL8; also known as IL-8) and chemokine (C-C motif) ligand 2 (CCL2; also known as monocyte chemotactic protein-1) and intracellular reactive oxygen species...... of neutrophils were investigated. RESULTS: Upon stimulation with P. gingivalis, neutrophils from subjects with LAgP and healthy controls released similar quantities of IL-6, TNF-α, CXCL8, CCL2 and intracellular ROS. The presence of RBCs amplified the release of IL-6, TNF-α and CCL2 statistically significant...

  7. Disassociated relation between plasma tumor necrosis factor-α, interleukin-6 and increased body weight in Amerindian women: A long-term prospective study of natural body weight variation and impaired glucose tolerance

    Directory of Open Access Journals (Sweden)

    Lindgärde Folke

    2010-06-01

    Full Text Available Abstract Background Inflammatory cytokines are linked to obesity-related insulin resistance and may predict type 2 diabetes independently of obesity. We previously reported that a majority of a cohort of 73 non-diabetic women with normal plasma (p-glucose with Amerindian heritage in Lima, Peru, during a 5-year period increased both body weight and p-glucose levels, yet p-insulin was unaltered. A high proportion of palmitoleic acid (16:1n-7 in serum (s and systolic blood pressure (SBP were independent predictors of high p-glucose. Whether cytokines also contributed is, however, not known. Methods During 5 years we prospectively investigated the relation between changed concentrations of p-tumor necrosis factor (TNF-α, p-interleukin (IL-6 and circulating insulin and glucose in relation to the natural variation of body weight. Study variables included anthropometric measurements, p-insulin, TNF-α, IL-6, SBP and the proportion of 16:1n-7 in s-fatty acid composition. Results Weight and waist differences correlated negatively to the difference in p-TNF-α but positively to differences in p-IL-6 and p-insulin, whereas the increase of p-glucose from baseline to follow-up did not correlate with changes in levels of the two cytokines. In multiple regression analysis changes of TNF-α and insulin contributed independently to the variance in weight. P-insulin at baseline and weight change were determinants of fasting p-insulin at follow-up. Multiple regression analysis revealed that weight change (t-value = - 2.42; P = 0.018 and waist change (t-value = 2.41; P = 0.019 together with S-16:1n-7 (p Conclusion Our prospective study of Amerindian women revealed disassociations between changes in p-TNF-α and p-IL-6 in relation to variation in body weight. A high proportion of s-16:1n-7, SBP at baseline together with weight and waist changes were independent predictors of p-glucose at follow-up. The exact role of the opposite effects and clinical impact of p

  8. Anti-Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to Anti-Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty-Five Patients.

    Science.gov (United States)

    Calvo-Río, Vanesa; Santos-Gómez, Montserrat; Calvo, Inmaculada; González-Fernández, M Isabel; López-Montesinos, Berta; Mesquida, Marina; Adán, Alfredo; Hernández, María Victoria; Maíz, Olga; Atanes, Antonio; Bravo, Beatriz; Modesto, Consuelo; Díaz-Cordovés, Gisela; Palmou-Fontana, Natalia; Loricera, Javier; González-Vela, M C; Demetrio-Pablo, Rosalía; Hernández, J L; González-Gay, Miguel A; Blanco, Ricardo

    2017-03-01

    To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents. We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient. TCZ appears to be a useful therapy for severe refractory JIA

  9. Mechanisms by Which Interleukin-6 Attenuates Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Ke-Hung Tsui

    2013-01-01

    Full Text Available Interleukin-6, a multifunctional cytokine, contributes to tumor cell proliferation and differentiation. However, the biological mechanisms that are affected by the expression of interleukin-6 in bladder cancer cells remain unclear. We evaluated the effects of interleukin-6 expression in human bladder carcinoma cells in vitro and in vivo. The results of interleukin-6-knockdown experiments in T24 cells and interleukin-6-overexpression experiments in HT1376 cells revealed that interleukin-6 reduced cell proliferation, migration, and invasion in vitro. Xenograft animal studies indicated that the overexpression of interleukin-6 downregulated tumorigenesis of bladder cells and that interleukin-6 knockdown reversed this effect. The results of RT-PCR, immunoblotting, and reporter assays indicated that the overexpression of interleukin-6 upregulated the expression of the mammary serine protease inhibitor (MASPIN, N-myc downstream gene 1 (NDRG1, and KAI1 proteins in HT1376 cells and that interleukin-6 knockdown reduced the expression of these proteins in T24 cells. In addition, results of immunoblotting assays revealed that interleukin-6 modulated epithelial-mesenchymal transitions by upregulating the expression of the E-cadherin, while downregulation N-cadherin and vimentin proteins. Our results suggest that the effects of interleukin-6 on the regulation of epithelial-mesenchymal transitions and the expressions of the MASPIN, NDRG1, and KAI1 genes attribute to the modulation of tumorigenesis in human bladder carcinoma cells.

  10. Circulating interleukin-6 and tumor necrosis factor receptor-1 predict ...

    African Journals Online (AJOL)

    EL-HAKIM

    history taking, clinical examination, and routine investigations (CBC, ESR,. CRP, Widal test and ... patients than in control children, and in resistant cases than in responsive cases (before and 5 ... appetite, constipation or diarrhea and abdominal pain. 2. Physical .... TNF-R1, during acute typhoid illness which decreased with ...

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S......-phase proportion of myeloma cells, which might increase the sensitivity to chemotherapy, we gave rhIL-6 followed by chemotherapy to 15 myeloma patients with refractory disease. A total of 25 treatment cycles were administered since ten patients had two cycles. The rhIL-6 dose was 2.5 (n = 3), 5.0 (n = 6) and 10...

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the pathophysiology of various human diseases such as type 2 diabetes and obesity. IL-6 signals via a heterodimeric receptor complex consisting of a soluble IL-6 alpha-subunit (IL-6 receptor [IL6R]) and a signal transducing subunit (gp130......-diabetic quantitative traits among Danish whites. By applying a recessive genetic model in a case-control study of 1,349 type 2 diabetic patients and 4,596 glucose-tolerant control subjects, we found a significant difference in genotype distribution (P = 0.008) and in allele frequency (Ala-allele 38.3% [95% CI 36.5...

  13. Increased serum levels of dehydroepiandrosterone (DHEA) and interleukin-6 (IL-6) in women with mild to moderate Alzheimer's disease.

    Science.gov (United States)

    Rasmuson, Sigbritt; Näsman, Birgitta; Olsson, Tommy

    2011-11-01

    It has been suggested that hypercortisolism contributes to the pathophysiology of Alzheimer's disease (AD), based on the fact that excess glucocorticoid exposure has potent adverse effects on the central nervous system. In contrast, dehydroepiandrosterone (DHEA) has been linked to a broad range of beneficial physiological effects including neuronal excitability and neuroprotection and even memory enhancing properties. Of note, proinflammatory cytokines are present in neuritic plaques (a hallmark of AD) and may regulate cortisol/DHEA release. In this exploratory study, we hypothesized that there is a flattened diurnal curve of cortisol and DHEA in mild to moderate AD, linked to increased cytokine levels. Diurnal profiles of cortisol, adrenocorticotropic hormone (ACTH), and DHEA were studied in 15 patients with mild to moderate AD (7 men and 8 women, 75.6 ± 5.5 years) and 15 healthy elderly controls (7 men and 8 women, 73.3 ± 5.8 years, respectively). Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and soluble TNF receptors were analyzed. Women with AD had significantly increased morning levels of ACTH, DHEA, and IL-6 compared to healthy elderly women. Cortisol levels were significantly increased in men with AD at 0300 h versus healthy elderly men, in spite of slightly decreased ACTH levels. Our data suggest important sex differences in hypothalamic-pituitary-adrenal (HPA) axis regulation and steroid hormone clearance in patients with AD. Increased secretion of IL-6 may have a contributory role in this difference.

  14. Increasing body condition score is positively associated interleukin-6 and monocyte chemoattractant protein-1 in Labrador retrievers.

    Science.gov (United States)

    Frank, Lauren; Mann, Sabine; Levine, Corri B; Cummings, Bethany P; Wakshlag, Joseph J

    2015-10-15

    The accumulation of excess body fat is a growing problem in dogs as well as people. Contrary to prior understanding of adipose tissue, fat is now considered to be an active endocrine organ that promotes a chronic low-grade inflammatory state often characterized by an increase in pro-inflammatory cytokines and chemokines. These have been implicated in several obesity-related disorders such as insulin resistance, cardiovascular disease, and neoplasia. The purpose of this study was to characterize fasting plasma cytokine concentrations in ninety-two healthy client-owned Labrador retriever dogs of various ages and body condition scores. The dogs were grouped according to body condition score (BCS) into three categories, lean, overweight and obese. The following cytokines and chemokines were evaluated; tumor necrosis factor-alpha, interleukin-2, interleukin-6, interleukin-8, and monocyte chemotactic protein-1 (TNF-α, IL-2, IL-6, IL-8, MCP-1). Our results indicated that fasting plasma IL-6 and MCP-1 concentrations are associated with increasing BCS. This data suggest that certain markers of inflammation increase with increasing body condition score, and that dogs, similar to humans, may be fostering a chronic inflammatory state due to obesity.

  15. Fatigue and interleukin-6 - a multi-faceted relationship.

    Science.gov (United States)

    Grygiel-Górniak, Bogna; Puszczewicz, Mariusz

    2015-01-01

    Many connective tissue diseases are characterized by fatigue, which is described in the literature as prostration, weakness, lassitude or asthenia. In many other diseases (autoimmune, neurologic or metabolic) fatigue impinges on daily activities and thus influences the quality of life. Different molecular backgrounds are involved in the development of fatigue. Not only does the immunosuppressive treatment of autoimmune diseases reduce fatigue, but also selective nutritional components may have an effect on secretion of cytokines which are responsible for development of the sensation of tiredness (e.g. secretion of interleukin-6). The beneficial influence of selected food components (such as polyunsaturated omega-3 fatty acids, nutritional antioxidants or adequate fat intake with the diet) on proinflammatory cytokine secretion has been demonstrated in many studies. In this review, the biochemical, neurological and nutritional aspects of fatigue in autoimmune diseases are underlined.

  16. Expression of Interleukin-6 in Mouse Uterus during Pregnancy

    Institute of Scientific and Technical Information of China (English)

    刘承权; 吴应积; 胡炎; DanielD,Carson

    1995-01-01

    Interleukin -6 (IL-6) is a cytokine with a wide variety of effects on cells involved in inflammation and pregnancy. Many cell types have been shown to produce IL-6 in vitro, however, very little is known about its source and role in vivo. By using in situ hybridization, we examined IL-6 cRNA expression in the mouse uterus-placental unit during pregnancy.The results showed that cRNA for IL-6 was not expressed on day 3 and 4 of pregnancy in uterine decidual cells, but was expressed in samples obtained on day 1 and day 5-11 of pregnancy. IL-6 expression was observed from undctectable on day 3-4 to a peak level on day 5-6 and then decreased on day 7-8. The expression of IL-6 cRNA in uterus during pregnancy implies that IL-6 plays an important physiological role in embryo implantation.

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

    Directory of Open Access Journals (Sweden)

    Werna Nontji

    2015-04-01

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

  18. 肿瘤坏死因子α和白细胞介素6基因启动子区多态性与精神分裂症的相关性研究%Association of the polymorphisms in the promoter region of tumor necrosis factor α and interleukin 6 genes with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    钟慧军; 彭亮; 朱永生; 党洁; 霍正浩

    2011-01-01

    目的 探讨肿瘤坏死因子α(tumor necrosis factorα,TNF-α)基因启动子区-308G/A、-857C/T和-1031T/C位点,白细胞介素6(interleukin-6)基因启动子-174G/C和-572C/G多态性与精神分裂症发生的相关性.方法 采用聚合酶链反应-限制性片段长度多态性分析方法检测346例精神分裂症患者、323名健康对照各个多态性位点的基因型,采用SPSS 13.0进行统计学分析.结果 TNF-α基因-857C/T位点的基因型及等位基因频率分布在精神分裂症组与正常对照组均存在统计学意义(P<0.05),其中,-857T的等位基因的频率在精神分裂症组均显著高于对照组(x2=9.414,P=0.002,OR=1.511,95%CI:1.160~1.969).-857C/T位点不同基因型患者之间的阳性和阴性症状量表总分及阴性症状差异存在显著性,且TT基因型的分值显著高于CC基因型(P<0.05).结论 TNF-α基因-857C/T位点可能与精神分裂症的发病存在关联,其中,-857T等位基因可能是易感基因,并且-857C/T位点与阳性和阴性症状量表评分中阴性症状存在关联.%Objective To investigate the relationship between the -308G/A, -857C/T and -1031T/C of tumor necrosis factor α gene (TNF-α), -174G/C and -572C/G of interleukin-6 gene (IL-6)polymorphisms and schizophrenia. Methods Genomic DNA was isolated from the venous blood leukocytes of 346 unrelated patients with schizophrenia and 323 healthy unrelated individuals (control group). All of the polymorphisms were genotyped by PCR-restriction fragment length polymorphisms (PCR-RFLP).Genotype and allele frequencies were analyzed by SPSS13. 0 software. Results There were significant differences in both allele and genotype frequencies of -857C/T of TNF-α gene between the schizophrenia and control groups (P<0. 05). The allele T of -857C/T in schizophrenia group was significantly higher than that in control group (x2 = 9.414, P= 0. 002, OR= 1.511, 95% CI: 1. 160-1. 969). In addition, there were significant differences in

  19. Effect of flurbiprofen on tumor necrosis factor-a, and interleukin-6 in children undergoing cardiopulmonary bypass%氟比洛芬对心肺转流室间隔缺损患儿肿瘤坏死因子-α、白细胞介素-6的影响

    Institute of Scientific and Technical Information of China (English)

    张颖; 顾尔伟

    2011-01-01

    目的:探讨氟比洛芬(flurbiprofen axetil,FA)对心肺转流(CPB)心内手术患儿血浆肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)水平的影响.方法:选择20例在CPB下行心内直视手术的室间隔缺损(ventricular septal defect,VSD)患儿,随机均分为FA组(F组)和对照组(C组).F组在麻醉后切皮前 15 min 给予 FA1 mg/kg,C组用等容量脂肪乳剂代替.分别于麻醉后切皮前10 min(基础值,T1)、主动脉开放10 min(T2)、CPB结束后 30 min(T3)、4 h(T4)、24 h(T5)、48 h(T6)测定血浆 TNF-α、IL-6水平.记录呼吸机辅助时间、围术期血管活性药物使用量等.结果:与T1相比,2组患者T3和T5时点TNF-α血浆水平均增高(P0.05);围术期多巴胺使用量差异有统计学意义(P0.05).结论:FA可抑制CPB期间促炎性细胞因子TNF-α、IL-6的生成和释放,有助于患儿围术期血流动力学稳定,促进患儿早期康复.%Objective :To investigate the influence of flurbiprofen on cytokines tumor necrosis factor-ct (TNF-α), and interleukin-6 (IL-6) in children undergoing cardiopulmonary bypass ( CPB ). Methods: In this pilot, prospective, and randomized double-blinded study, twenty children with cardiac function class I -Ⅱ scheduled for repairing ventricular septal defect were divided into two groups:children in flurbiprofen group( F group,n = 10)were received 1 mog/kg flurbiprofen 15 min before skin incision and children in control group ( C group, n = 10 ) were received 0. 1 mL/kg intralipid instead of flurbiprofen. Blood samples were taken 10 min before skin incision(T1 ), 10 min after aorta declamped ( T2 ), 30 min ( T3 ), 4 h ( T4 ), 24 h ( T5 ), 48 h ( T6 ) after termination of CPB for determination of plasma TNF-α and IL-6 concentration. Results: The plasma TNF-α levels was higher at T3 and T5 compared to baseline (P < 0.05 -P <0.01),but F group was lower than in C group at T3(P <0.01). IL-6 was higher during T2 -T6 in C

  20. 黄连温胆汤加减对代谢综合征大鼠肿瘤坏死因子-α和白介素-6的影响%Effect of Huanglianwendan Decoction on Tumornecrosis Factor - α and Interleukin -6 in Metabolic Syndrome Rats

    Institute of Scientific and Technical Information of China (English)

    刘莉; 许锋锐; 芦晔

    2012-01-01

    目的 观察黄连温胆汤加减对代谢综合征(MS)大鼠血清肿瘤坏死因子(TNF -α)和白介素-6(IL-6)的影响.方法 采用高盐高脂高糖饲料喂养,诱导实验性MS大鼠模型.大鼠随机分为模型组、黄连温胆汤加减高剂量组、黄连温胆汤加减低剂量组、盐酸二甲双胍对照组和空白组.生物化学法检测血糖、血清胰岛素的水平,放免法检测血浆TNF -α、IL -6水平.结果 模型组血浆血清TNF -α、IL -6和胰岛素抵抗指数水平显著增加(P<0.01);黄连温胆汤加减高剂量组血清TNF-α、IL-6和胰岛素抵抗指教水平降低(P<0.05).结论 黄连温胆汤加减对MS大鼠胰岛素抵抗指数具有降低作用,其机制可能与降低TNF-α、IL-6水平有关.%Objective To observe the effect of HUANCUANWENDAN decoction on expression of interleukin -6 and tumor necrosis factor - ain order to explore the function of the tre - atment mechanism of Insulin resistance. Methods Sixty male SD rats were randomly divided into normal diet group (n = 10)and high fat high salt and high glucose diet gr -oup (n = 50) to induce metabolic syndrome model then metabolic syndrome rate were got 37 successfully, and then these 37 metabolic syndrome rats were randomly divi - ded into model group (n =9) , high dose HUANGLIANWENDAN decoction group (n = 10) , low dose HUANGLIANWENDAN decoction group (n = 10) and DM-BG group (n = 8) , normal diet group and model group were feed physiologic - al saline, fasting blood glucose ( FBC),fasting insulin ( FINS) , interleukin - 6 (IL - 6) and tumor necrosis factor - α( TNF - α) in the serum were detected by enzymatic method, radioimmunoas - say, or enzyme - linked immunosorbent assay after 4weeks. Results In model group level of TNF - α,IL - 6in blood and IR index are higher than normal diet group ( P < 0. 01); The data in high dose HUANGLIANWENDAN decoction is depressed evidently ( P < 0. 05 ). Conclusion HUANGLIANWENDAN decoction can regulate IR index

  1. Assessment of the role of interleukin-6 in diagnosis of hepatocellular carcinoma.

    Science.gov (United States)

    El-Folly, Runia Fouad; El-Kabarity, Rania Hamdy; Arafa, Naglaa A

    2010-01-01

    Interleukin-6 (IL-6) is a promising tumor marker for hepatocellular carcinoma; HCC. IL-6 may help to identify a subset of HCC patients with low alpha-fetoprotein (AFP) level, and may serve as complementary tumor marker, however, this has to be clarified. This study assesses the value of measuring serum level of interleukin-6 in patients with chronic liver disease and HCC, and evaluates its sensitivity and specificity in comparison to AFP in early diagnosis of HCC. Seventy five patients with chronic liver disease (CLD) with or without HCC and 25 healthy controls were included. Patients were divided into Group I: 25 patients with CLD but no evidence of HCC. Group II: 25 patients with HCC on top of post-viral hepatitic with elevation in AFP (> 200 ng); and Group III: 25 patients with HCC on top of post-viral hepatitic but without elevation in AFP (< 200 ng). Analysis of the mean serum IL-6 levels revealed a statistically significant difference between all groups (P < 0.01). A significant positive correlation was found between mean levels of IL- 6 & AFP in HCC (P < 0.05), the mean IL-6 levels in patients with Child classification C was higher than in those with Child A and B.After adjustment using multiple logistic regressions, only loss of weight and AFP were found to be significantly associated with HCC (P < 0.05). It is concluded that the diagnostic value of IL-6 increased when it is associated with AFP measurement. Combining the two markers can provide a new perspective in the diagnosis of HCC.

  2. Salivary Interleukine 6 and its role on developing periodentitis

    Directory of Open Access Journals (Sweden)

    Thana Mohammed Juda

    2016-03-01

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

  3. Parathyroid hormone mediates hematopoietic cell expansion through interleukin-6.

    Directory of Open Access Journals (Sweden)

    Flavia Q Pirih

    Full Text Available Parathyroid hormone (PTH stimulates hematopoietic cells through mechanisms of action that remain elusive. Interleukin-6 (IL-6 is upregulated by PTH and stimulates hematopoiesis. The purpose of this investigation was to identify actions of PTH and IL-6 in hematopoietic cell expansion. Bone marrow cultures from C57B6 mice were treated with fms-like tyrosine kinase-3 ligand (Flt-3L, PTH, Flt-3L plus PTH, or vehicle control. Flt-3L alone increased adherent and non-adherent cells. PTH did not directly impact hematopoietic or osteoclastic cells but acted in concert with Flt-3L to further increase cell numbers. Flt-3L alone stimulated proliferation, while PTH combined with Flt-3L decreased apoptosis. Flt-3L increased blasts early in culture, and later increased CD45(+ and CD11b(+ cells. In parallel experiments, IL-6 acted additively with Flt-3L to increase cell numbers and IL-6-deficient bone marrow cultures (compared to wildtype controls but failed to amplify in response to Flt-3L and PTH, suggesting that IL-6 mediated the PTH effect. In vivo, PTH increased Lin(- Sca-1(+c-Kit(+ (LSK hematopoietic progenitor cells after PTH treatment in wildtype mice, but failed to increase LSKs in IL-6-deficient mice. In conclusion, PTH acts with Flt-3L to maintain hematopoietic cells by limiting apoptosis. IL-6 is a critical mediator of bone marrow cell expansion and is responsible for PTH actions in hematopoietic cell expansion.

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

    Science.gov (United States)

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

    2016-03-01

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

  5. Curcumin protects against interleukin-6-induced rapid Ca2+ influx in rat hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Qinying Deng; Tao Huang; Hongmei Tang; Xingming Zhong; Sujian Xia; Xiangcai Wei; Jun Dong

    2011-01-01

    The current study sought to investigate the potential protective action of curcumin against interleukin-6-induced injury in rat hippocampal neurons. The results revealed that interleukin-6 induced typical cellular injury, such as the swelling of cell bodies and increased Ca2+ concentration. After administration of curcumin, interleukin-6-induced neurons recovered to a normal state, and the fluorescence intensity of Ca2+ gradually returned to normal. These findings suggest that curcumin exerts a protective effect on hippocampal neurons of rats. In addition, our results suggest that the protective effect of curcumin involves prevention of the rapid Ca2+ influx induced by interleukin-6, which maintains Ca2+ homeostasis.

  6. Cytokines and clustered cardiovascular risk factors in children

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Müller, Klaus; Eiberg, Stig

    2010-01-01

    The aim was to evaluate the possible role of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein (CRP), low fitness, and fatness in the early development of clustering of cardiovascular disease (CVD) risk factors and insulin resistance. Subjects for this cross...

  7. Self-compassion as a predictor of interleukin-6 response to acute psychosocial stress.

    Science.gov (United States)

    Breines, Juliana G; Thoma, Myriam V; Gianferante, Danielle; Hanlin, Luke; Chen, Xuejie; Rohleder, Nicolas

    2014-03-01

    We examined the hypothesis that self-compassion is associated with lower levels of stress-induced inflammation. On two consecutive days, plasma concentrations of interleukin-6 (IL-6) were assessed at baseline and at 30 and 120 min following exposure to a standardized laboratory stressor in a sample of 41 healthy young adults. Participants who were higher in self-compassion exhibited significantly lower day 1 IL-6 responses, even when controlling for self-esteem, depressive symptoms, demographic factors, and distress. Self-compassion was not related to day 2 IL-6 response but was inversely related to day 2 baseline IL-6 levels, and to increase in baseline IL-6 from day 1 to day 2. These findings suggest that self-compassion may serve as a protective factor against stress-induced inflammation and inflammation-related disease.

  8. SERUM YKL-40 CORRELATES WITH SERUM INTERLEUKIN-6 IN MULTIPLE MYELOMA

    DEFF Research Database (Denmark)

    Mylin, Anne Kjærsgaard; Andersen, Niels Frost; Johansen, Julia S.

    2007-01-01

    identified using immunohistochemical staining for CD34-positive endothelial cells. The serum concentrations of the angiogenic cytokines interleukin-6 (S-IL-6), hepatocyte growth factor (S-HGF) and basic fibroblast growth factor (S-bFGF) were measured in both peripheral blood (PB) and BM. Results. 57......-13)   31 11 (0-43) >0.0001 BM 9 3 (1-11)   10 9(1-37) 0.04 S-HGF, ng/L             PB 23 1 (0-4)   30 3 (0-43) 0.03 BM 4 8 (3-17)   8 16 (3-43) 0.5 S-bFGF, ng/L             PB 23 5 (1-25)   31 7 (1-31) 0.6 BM 7 163 (131-589)   8 55 (36-198) 0.008 -- page break --...

  9. Recombinant production of human interleukin 6 in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Henrik Nausch

    Full Text Available In this study, we compared basic expression approaches for the efficient expression of bioactive recombinant human interleukin-6 (IL6, as an example for a difficult-to-express protein. We tested these approaches in a laboratory scale in order to pioneer the commercial production of this protein in Escherichia coli (E. coli. Among the various strategies, which were tested under Research and Development (R&D conditions, aggregation-prone IL6 was solubilized most effectively by co-expressing cytoplasmic chaperones. Expression of a Glutathion-S-Transferase (GST fusion protein was not efficient to increase IL6 solubility. Alteration of the cultivation temperature significantly increased the solubility in both cases, whereas reduced concentrations of IPTG to induce expression of the T7lac-promotor only had a positive effect on chaperone-assisted expression. The biological activity was comparable to that of commercial IL6. Targeting the expressed protein to an oxidizing environment was not effective in the generation of soluble IL6. Taken together, the presence of chaperones and a lowered cultivation temperature seem effective to isolate large quantities of soluble IL6. This approach led to in vivo soluble, functional protein fractions and reduces purification and refolding requirements caused by downstream purification procedures. The final yield of soluble recombinant protein averaged approximately 2.6 mg IL6/liter of cell culture. These findings might be beneficial for the development of the large-scale production of IL6 under the conditions of current good manufacturing practice (cGMP.

  10. Interleukin-6 as an early marker for fat embolism

    Directory of Open Access Journals (Sweden)

    Yoga R

    2009-06-01

    Full Text Available Abstract Background Fat Embolism is a complication of long bone fractures, intramedullary fixation and joint arthroplasty. It may progress to fat embolism syndrome, which is rare but involves significant morbidity and can occasionally be fatal. Fat Embolism can be detected at the time of embolization by transoesophageal echocardiography or atrial blood sampling. Later, a combination of clinical signs and symptoms will point towards fat embolism but there is no specific test to confirm the diagnosis. We investigated serum Interleukin-6 (IL-6 as a possible early marker for fat embolism. Methods An animal study was conducted to simulate a hip replacement in 31 adult male Sprague Dawley rats. The procedure was performed under general anesthesia and the animals divided into 3 groups: control, uncemented and cemented. Following surgery and recovery from anaesthesia, the rats allowed to freely mobilize in their cages. Blood was taken before surgery and at 6 hours, 12 hours and 24 hours to measure serum IL-6 levels. The rats were euthanized at 24 hours and lungs removed and stained for fat. The amount of fat seen was then correlated with serum IL-6 levels. Results No rats in the control group had fat emboli. Numerous fat emboli were seen in both the uncemented and cemented implant groups. The interleukin levels were raised in all groups reaching a peak at 12 hours after surgery reaching 100 pg/ml in the control group and around 250 pg/ml in the uncemented and cemented implant groups. The IL-6 levels in the control group were significantly lower than any of the implant groups at 12 and 24 hours. At these time points, the serum IL-6 correlated with the amount of fat seen on lung histology. Conclusion Serum IL-6 is a possible early marker of fat embolism.

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

    Science.gov (United States)

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

    2014-01-01

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

  12. Salivary and serum interleukin-6 levels in proliferative verrucous leukoplakia.

    Science.gov (United States)

    Bagan, Leticia; Sáez, Guillermo T; Tormos, M Carmen; Labaig-Rueda, Carlos; Murillo-Cortes, Judith; Bagan, Jose V

    2016-05-01

    Cytokines and chemokines have been analysed in patients with oral squamous cell carcinoma and potentially malignant disorders. We selected interleukin-6 (IL-6) because it is a multifunctional interleukin reported to be altered in potentially malignant oral disorders and in malignant lesions. To date, this has not been evaluated or tested in proliferative verrucous leukoplakia (PVL), however. This study aimed to analyse the differences in serum and saliva IL-6 levels among patients with PVL, oral squamous cell carcinoma (OSCC) and healthy controls and to examine the relationship between salivary IL-6 levels and the extent of the verrucous area. Using an enzyme-linked immunosorbent assay, we determined the serum and saliva IL-6 levels in three groups: 20 patients with PVL, 20 with OSCC and 20 healthy controls. There were significant (p verrucous areas (p = 0.01). In the OSCC group, there was a significant difference in the saliva IL-6 levels between patients with and without lymph node metastasis at diagnosis (p = 0.02). We found that patients with OSCC had the highest salivary and serum IL-6 levels, while PVL had lower values than OSCC, but higher than the controls, and these altered levels were associated with the extent of the verrucous areas. Salivary and plasma IL-6 are altered in patients with PVL, with more extensive verrucous areas being associated to the highest IL-6 levels. This could be a significant tool for monitoring patients with PVL, their progression to more advances stages and their recurrences.

  13. Interleukin-6 gene polymorphism -174G/C influences plasma lipid levels in women.

    Science.gov (United States)

    Henningsson, Susanne; Håkansson, Anna; Westberg, Lars; Baghaei, Fariba; Rosmond, Roland; Holm, Göran; Ekman, Agneta; Nissbrandt, Hans; Eriksson, Elias

    2006-11-01

    Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) have been associated with cardiovascular risk factors. The objective of this study was to investigate potential associations between the promoter polymorphism IL-6 -174G/C and the following indices of metabolism: BMI, waist-to-hip ratio, and plasma levels of IL-6, cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, leptin, and C-reactive protein in 252 42-year-old women and 245 51-year-old men. Subgroups were also studied 5 years later. The CC genotype of the IL-6 polymorphism was associated with lower levels of cholesterol and low-density lipoprotein (p polymorphism on metabolic indices in women and men. None of the associations between IL-6 genotype and lipid pattern seemed to result from an effect of the polymorphism on IL-6 plasma levels.

  14. 二甲双胍对糖耐量异常非酒精性脂肪性肝病患者 IL-6、TNF-α的影响%Effect of metformin on the level of serum interleukin-6 and tumor necrosis factor-αof impaired glucose tolerance patients with non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    曾红萍; 徐定婷

    2015-01-01

    Objective To evaluate the efficacy of metformin on the level of interleukin-6 and tumor necrosis factor-αof impaired glucose tolerance patients with non-alcoholic fatty liver disease .Method 160 impaired glucose tolerance patients with non-alcoholic fatty liver disease were firstly divided into an experimental group (n=90) and a control group(n=70). On the basis of strict diet control and physical exercise , the experimental group was given metformin 1500 mg per day for a period of 24 weeks.The control group was treated with polyene phosphatidylcholine capsules 456mg per day also for a period of 24 weeks.Results After 24 weeks of treatment, the level of body mass index (BMI), anine aminotrans-ferase (ALT), fasting blood glucose (FPG), insulin, homeostasis model assessment-insulin resistance (HOMA IR) of the experimental group decreased more significantly than those of the control group (P0.05).Conclusion The metformin treatment could improve the glucose metabolism indexes and insulin resistance of impaired glucose tolerance patients with non-alcoholic fatty liver disease , reduce liver enzyme and inflammatory cytokines , improve liver function , and lessen the degree of inflammation in liver .%目的:观察二甲双胍对糖耐量异常非酒精性脂肪性肝病( nonalcoholic fatty liver disease , NAFLD)患者IL-6、TNF-α的影响。方法将160例糖耐量异常NAFLD患者随机分为观察组( n=90)和对照组( n=70)。在严格控制饮食和运动的基础上,观察组加用二甲双胍1500 mg/d,对照组加用多烯磷脂酰胆碱胶囊456 mg/d,均治疗24周。结果治疗24周后,与对照组比较,观察疗组患者BMI、ALT、FPG、insulin、HOMA-IR、hs-CRP、TNF-α和IL-6水平均显著降低(P<0.05);两组间AST水平差异无统计学意义(P>0.05)。结论二甲双胍能改善糖耐量异常NAFLD患者糖代谢指标和胰岛素抵抗,降低肝酶和炎症细胞因子水平。

  15. Tumour necrosis factor-alpha and interleukin-8 inhibit neutrophil migration in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    F. Q. Cunha

    1992-01-01

    Full Text Available Pretreatment of human neutrophils with recombinant tumour necrosis factor-alpha (rTNF-α and/or interleukin-8 (rIL-8, but not with either transforming growth factor-beta, interleukin-6 or interferon-gamma, rendered these cells less responsive to FMLP, in microchemotaxis assays. This inhibitory effect was dose dependent and more powerful when neutrophils were pretreated with a mixture of both cytokines. Intravenous injection of human rIL-8 (hrIL-8 and/or murine rTNF-α (mrTNF-α also significantly reduced in vivo neutrophil migration into peritoneal cavities of rats stimulated with carrageenan. These data suggest that the defect in neutrophil migration during septicaemia or endotoxaemia may be the result of the continuous release of IL-8 and TNF-α into the circulation. Thus, either the selective control or blockade of releasing of these cytokines as well as of its effects on neutrophils may be clinically useful in reestablishing the cell defence mechanisms.

  16. Effect of osteoprotegerin in combination with interleukin-6 on inhibition of osteoclast differentiation

    Directory of Open Access Journals (Sweden)

    WANG Xin

    2013-10-01

    Full Text Available 【Abstract】Objective: To observe the effect of recombinant interleukin-6 (IL-6 and osteoprotegerin (OPG on inhibiting bone absorption induced by receptor activa- tor for nuclear factor-κB ligand (RANKL in murine osteo- clast precursor cells (OCPs model. Methods: RAW 264.7 cells were solely treated with 50 ng/ml RANKL for 1 day, and then they were divided into three groups: RANKL (control group, RANKL+IL-6 (IL-6 group and RANKL+IL-6+OPG (combination group. These cells were harvested and investigated by means of HE stain- ing under light microscope after consecutive 9 days. Furthermore, staining tartrate-resistant acid phosphatase (TRAP-positive multinucleated cells were detected by inverted phase contrast microscope. The absorption pits of bone slices were observed under scanning electron microscope. Results: The number of mature osteoclast cells in control group was more than that in IL-6 alone or IL-6 com- bined with OPG group (P<0.05. Interestingly, this experi- ment has also demonstrated that there was a large number of TRAP-positive multinucleated osteoclasts (more than 3 nuclei and several bone absorption formation in the con- trol group, whereas the outcome was completely different in both IL-6 group and IL-6+OPG group (P<0.05. Conclusion: IL-6 can suppress the differentiation of mature osteoclasts as directly adding it into the RAW 264.7 cells induced by 50 ng/ml RANKL, and further the effect of osteolysis is remarkably reduced. When treatment with IL- 6 combined with OPG, a more effective strategy for the treat- ment of osteoporosis is reached. Key words: Osteoclasts; Osteoporosis; Osteopro- tegerin; RANK ligand; Interleukin-6

  17. Tocilizumab improved clinical symptoms of a patient with systemic tophaceous gout who had symmetric polyarthritis and fever: An alternative treatment by blockade of interleukin-6 signaling

    Directory of Open Access Journals (Sweden)

    Sho Mokuda

    2014-01-01

    Full Text Available Chronic tophaceous gout is the end stage of gout. We employed a blockade of interleukin-6 signaling therapy by tocilizumab instead of anakinra, an interleukin-1 receptor antagonist, for a 61-year-old Japanese woman diagnosed with tophaceous gout. Laboratory data showed that serum interleukin-6 concentration was elevated. Serum interleukin-1β concentration was under the detectable level, although serum uric acid was elevated due to renal dysfunction. The secretion patterns of interleukin-1β, tumor-necrosis factor-α, interleukin-6, and interleukin-8 from peripheral mononuclear cells isolated from the patient exhibited no remarkable differences compared with those of healthy volunteers. After treatment with the interleukin-6 receptor antagonist tocilizumab, serum interleukin-6 concentration decreased followed by improved clinical symptoms, such as reduced size of the subcutaneous nodules, no fever, and no acute gouty attacks during the treatment. Our case suggests that tocilizumab markedly improves clinical and laboratory manifestations in tophaceous gout with arthritis and fever as well as interleukin-1 blockade therapy.

  18. [Diagnostic value of interleukin 6 for neonatal sepsis: a Meta analysis].

    Science.gov (United States)

    Hu, Jing; DU, Peng-Fei; Bei, Dan-Dan

    2015-11-01

    To evaluate the diagnostic value of interleukin 6 for neonatal sepsis. The databases of CNKI, VIP, Wangfang, Pubmed, Embase, Web of Science, Cochrane Library were searched (by September 2014) to identify relevantly published studies about estimating the diagnostic value of interleukin 6 for neonatal sepsis. QUADAS tools were used for quality evaluation of the studies. A Meta analysis was performed by employing Meta Disc 1.4 and Stata11.0 software. Heterogeneity of the included articles was tested to select proper efficacy model for calculating pooled weighted sensitivity, specificity and 95%CI. Summary receiver operating characteristic (SROC) curve was made and the area under the curve and Q(*) index were calculated. A total of 33 studies including 3 135 neonates were enrolled. The sensitivity and specificity of interleukin 6 for the diagnosis of neonatal sepsis were 0.79 (95%CI: 0.76-0.81) and 0.83 (95%CI: 0.81-0.85) respectively. The area under SROC curve of interleukin 6 for the diagnosis of neonatal sepsis was 0.89 and Q(*) index was 0.83. The post-test probability of diagnosing neonatal sepsis indicated by negative interleukin 6 was 5%, while that of positive interleukin 6 was 60%. Interleukin 6 measurement is useful for the diagnosis of neonatal sepsis with a high sensitivity and specificity.

  19. Genomic organization and chromosomal localization of the human and mouse genes encoding the alpha receptor component for ciliary neurotrophic factor.

    Science.gov (United States)

    Valenzuela, D M; Rojas, E; Le Beau, M M; Espinosa, R; Brannan, C I; McClain, J; Masiakowski, P; Ip, N Y; Copeland, N G; Jenkins, N A

    1995-01-01

    Ciliary neurotrophic factor (CNTF) has recently been found to share receptor components with, and to be structurally related to, a family of broadly acting cytokines, including interleukin-6, leukemia inhibitory factor, and oncostatin M. However, the CNTF receptor complex also includes a CNTF-specific component known as CNTF receptor alpha (CNTFR alpha). Here we describe the molecular cloning of the human and mouse genes encoding CNTFR. We report that the human and mouse genes have an identical intron-exon structure that correlates well with the domain structure of CNTFR alpha. That is, the signal peptide and the immunoglobulin-like domain are each encoded by single exons, the cytokine receptor-like domain is distributed among 4 exons, and the C-terminal glycosyl phosphatidylinositol recognition domain is encoded by the final coding exon. The position of the introns within the cytokine receptor-like domain corresponds to those found in other members of the cytokine receptor superfamily. Confirming a recent study using radiation hybrids, we have also mapped the human CNTFR gene to chromosome band 9p13 and the mouse gene to a syntenic region of chromosome 4.

  20. Detection of circulant tumor necrosis factor-alpha , soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    Elzinandes LA Braga

    2001-02-01

    Full Text Available Pro-inflammatory cytokines are believed to play an important role in the pathogenesis of dengue infection. This study reports cytokine levels in a total of 54 patients examined in Recife, State of Pernambuco, Brazil. Five out of eight patients who had hemorrhagic manifestations presented tumor necrosis factor-alpha (TNF-alpha levels in sera which were statistically higher than those recorded for controls. In contrast, only one out of 16 patients with mild manifestations had elevated TNF-alpha levels. The levels of interleukin-6 (IL, IL-1beta tested in 24 samples and IL-12 in 30 samples were not significantly increased. Interferon-g was present in 10 out of 30 patients with dengue. The data support the concept that the increased level of TNF-alpha is related to the severity of the disease. Soluble TNF receptor p75 was found in most patients but it is unlikely to be related to severity since it was found with an equivalent frequency and levels in 15 patients with dengue fever and another 15 with dengue hemorrhagic fever.

  1. Human monocyte elastolytic activity, the propeptides of types I and III procollagen, proteoglycans, and interleukin-6 in synovial fluid from patients with arthritis

    DEFF Research Database (Denmark)

    Jensen, H S; Jensen, L T; Saxne, T;

    1991-01-01

    elastolytic activity, using the levels of synovial fluid interleukin-6 and serum C reactive protein as additional markers of cell activation. Proteoglycan levels were measured as an indication of cartilage degradation and the types I and III procollagen propeptides as markers of synovial membrane turnover. We...... found that elastolysis by live M phi and the levels of interleukin-6 and C reactive protein correlated significantly with proteoglycan concentrations but not with the procollagen propeptides. These findings suggest that human M phi elastolytic activation is a biologically relevant factor in cartilage...

  2. Fator de inibição da migração de macrófagos e interleucina-6 na síndrome de esmagamento: analogia com gravidade? Relato de casos Macrophage migration inhibitory factor and interleukin-6 in crush syndrome: analogy with severity? Case reports

    Directory of Open Access Journals (Sweden)

    Rita C. Vianna de Azevedo

    2007-12-01

    . Interleukin-6 (IL-6 is a proinflammatory cytokine that plays an important role in the initial inflammatory response to trauma and the development of early and late multiple organ dysfunction syndrome (MODS. Crush syndrome has been described as the systemic manifestation of muscle cell damage resulting from pressing or crushing. There are few data about MIF and IL-6 in crush syndrome. The aim of this study was to report four cases of crush syndrome, measuring seric levels of MIF and IL-6 and its correlation with severity. CASES REPORTS: Four patients suffering from crush syndrome after an accident with an explosive artifact were enrolled in the study. APACHE II score was checked at admission. It was collected serum sample of these patients during six consecutive days. Serum MIF, IL-6 and creatine kinase (CK were measured. Sepsis-related organ failure assessment (SOFA score was evaluated concomitantly. Data were analyzed. CONCLUSIONS: The variations observed in the CK measures were followed by alterations in the cytokines' level and at the SOFA score, suggesting interdependence between those factors. Other articles have already demonstrated similar results. Although the use of cytokines as biomarkers of severity in trauma is matter of interest, we need large studies with a higher number of patients to validate this observation.

  3. Baclofen influences lipopolysaccharide-mediated interleukin-6 release from murine pituicytes

    DEFF Research Database (Denmark)

    Kjeldsen, Tine H; Hansen, Erik W; Christensen, Jens D

    2002-01-01

    -6 release from pituicytes. Cultured murine pituicytes were stimulated for 24 h with lipopolysaccharide (0.5 ng/ml) to give a significant interleukin-6 release compared to control. The interleukin-6 release was significantly potentiated by the GABA(B) receptor agonist (R)-4-amino-3-(4-chlorophenyl......Pituicytes, the glial cells of the neurohypophysis, secrete interleukin-6 upon stimulation with various inflammatory mediators, i.e. lipopolysaccharide. Previous studies have identified several receptors on pituicytes. This study investigates the effect of GABA(B) receptor activation on interleukin......) butanoic acid (R-baclofen; 10, 100 or 500 microM). However, R-baclofen itself (10, 100 or 500 microM) did not stimulate the interleukin-6 secretion. Furthermore, the potent GABA(B) receptor antagonists 3-[[(3,4-Dichlorophenyl)methyl]amino]propyl]diethoxymethyl) phosphinic acid (CGP52432; 30 or 300 micro...

  4. A citrus flavonoid, 6-demethoxytangeretin, suppresses production and gene expression of interleukin-6 in human mast cell-1 via anaplastic lymphoma kinase and mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Kim, Young-Mi; Chae, Hee-Sung; Lee, Eun Joo; Yang, Min Hye; Park, Jin Hee; Yoon, Kee Dong; Kim, Jinwoong; Ahn, Hee Chul; Choi, Young Hee; Chin, Young-Won

    2014-01-01

    Citrus species has been traditionally used in Korea for the treatment of coughing, sputum and dyspepsia. Of the known citrus flavonoids, 6-demethoxytangeretin was reported to exert anti-inflammatory activity. In order to determine the anti-allergic activity of 6-demethoxytangeretin, we examined whether or not 6-demethoxytangeretin was able to suppress activation of the human mast cell line, HMC-1, induced by phorbol 12-myristate 13-acetate (PMA) plus A23187. Interleukin-6 production and relevant gene expression in activated HMC-1 cells were determined by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Also, the involvement of the anaplastic lymphoma kinase (ALK) and mitogen-activated protein kinases (MAPKs) in activated HMC-1 cells were studied. 6-Demethoxytangeretin suppresses interleukin-6 production, tumor necrosis factor-alpha gene expression, ALK and MAPKs in HMC-1 cells stimulated by PMA plus A23187. Therefore, it was evident that 6-demethoxytangeretin suppressed activation of HMC-1 cells by PMA plus A23187 by inhibiting the activity of ALK and MAPKs and subsequently suppressing gene expression, which suggest that 6-demethoxytangeretin may be involved in the regulation of mast cell-mediated inflammatory responses.

  5. Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions

    DEFF Research Database (Denmark)

    Smolen, Josef S; Schoels, Monika M; Nishimoto, Norihiro

    2013-01-01

    BACKGROUND: Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other in...

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

    Science.gov (United States)

    Sundén, Fredrik; Butler, Daniel; Wullt, Björn

    2017-07-01

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

  7. The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer

    Science.gov (United States)

    Ramsey, S; Lamb, G W A; Aitchison, M; McMillan, D C

    2006-01-01

    The systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, is a stage-independent prognostic factor in patients undergoing curative nephrectomy for localised renal cancer. However, it is not clear whether the systemic inflammatory response arises from the tumour per se or as a result of an impaired immune cytokine response. The aim of the present study was to examine C-reactive protein, interleukin-6 and interleukin-10 concentrations before and following curative resection of renal cancer. Sixty-four patients with malignant renal disease and 12 with benign disease, undergoing resection were studied. Preoperatively, a blood sample was collected for routine laboratory analysis with a further sample stored before analysis of interleukin-6 and interleukin-10 using an enzyme-linked immunosorbent assay (ELISA) technique. The blood sampling procedure and analyses were repeated at approximately 3 months following resection. Circulating concentrations of both interleukin-6 and interleukin (P⩽0.01) were higher and a greater proportion were elevated (Pinterleukin-10 concentrations were higher (Pinterleukin-10 (r2=0.24, P=0.001). Following nephrectomy the proportion of patients with elevated C-reactive protein, interleukin-6 and interleukin-10 concentrations did not alter significantly. An elevated preoperative C-reactive protein was associated with increased tumour stage, interleukin-6 and interleukin-10 concentrations. However, resection of the primary tumour did not appear to be associated with significant normalisation of circulating concentrations of C-reactive protein, interleukin-6 or interleukin-10. Therefore, the presence of systemic inflammatory response is unlikely to be solely be determined by the tumour itself, but may be as a result of an impaired immune cytokine response in patients with renal cancer. PMID:17003778

  8. Induction of prostaglandin E(2) and interleukin-6 in gingival fibroblasts by oral biofilms.

    Science.gov (United States)

    Belibasakis, Georgios N; Guggenheim, Bernhard

    2011-12-01

    Polymicrobial oral biofilms attaching on tooth surfaces can trigger inflammatory responses by the neighbouring tooth-supporting periodontal tissues. An excessive inflammatory response can cause destruction of the periodontal tissues, including the alveolar bone, thus resulting in periodontitis. Mediators of inflammation, such as prostaglandin E(2) (PGE(2) ) and interleukin-6, are primary regulators of alveolar bone destruction in periodontitis. The present study aimed to comparatively investigate the effects of in vitro supragingival and subgingival biofilms, on the regulation of PGE(2) and interleukin-6 in human gingival fibroblasts. The cells were challenged with culture supernatants of the two biofilms for 6 h. Cyclo-oxygenase (COX)-2, an enzyme responsible for the conversion of PGE(2) , and interleukin-6 gene expression were analysed by quantitative real-time PCR. The production of PGE(2) and interleukin-6 by the cells was analysed by ELISA. While the supragingival biofilm did not induce significant changes, the subgingival biofilm caused an 8.6- and 2.9-fold enhancement of COX-2 and interleukin-6 gene expression, respectively, and a 72.5- and 1.5-fold enhancement of PGE(2) and interleukin-6 production, respectively. In conclusion, subgingival biofilms are potent inducers of PGE(2) in gingival fibroblasts, providing further mechanistic insights into the association of subgingival biofilms with bone resorption periodontitis.

  9. Increased methylation of interleukin 6 gene is associated with obesity in Korean women.

    Science.gov (United States)

    Na, Yeon Kyung; Hong, Hae Sook; Lee, Won Kee; Kim, Young Hun; Kim, Dong Sun

    2015-05-01

    Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor α (TNFα), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals (BMI ≥ 30 kg/m(2)) showed significantly increased hypermethylation for IL6 gene compared to normal weight (BMI genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship.

  10. Mortality, malnutrition, and atherosclerosis in ESRD: what is the role of interleukin-6?

    Science.gov (United States)

    Stenvinkel, Peter; Barany, Peter; Heimbürger, Olof; Pecoits-Filho, Roberto; Lindholm, Bengt

    2002-05-01

    There is growing evidence that increased plasma concentrations of CRP strongly predict cardiovascular death in both non-renal and renal patient populations. The interleukin-6 (IL-6) system activity, which is the major mediator of the acute phase response, is often markedly up-regulated in uremic patients and has also been shown to predict outcome. This raises the issue of whether or not IL-6 per se may contribute to increased mortality from malnutrition and atherosclerotic cardiovascular disease in uremic patients. The causes of elevated IL-6 levels in the uremic circulation are not fully understood, although a number of factors prevalent in uremic patients, such as hypertension, adiposity, infections, and chronic heart failure may all contribute. However, factors associated with the dialysis procedure, such as bioincompatibility and non-sterile dialysate, may stimulate IL-6 production. Furthermore, available evidence suggests that genetic factors may also have an impact on circulating plasma IL-6 levels. We advance the hypothesis that IL-6 may play a central role in the genesis of inflammatory-driven malnutrition and that it may be regarded as a significant proatherogenic cytokine. This hypothesis may provide a rationale to test if targeted anti-cytokine therapy may be one way to combat the unacceptable high cardiovascular mortality rate among dialysis patients.

  11. Correlation between interleukin - 1 β, interleukin - 6, tumor necrosis factor - α and attention deficit hyperactivity disorder%IL-1β、IL-6、TNF-α与注意缺陷多动障碍的相关性

    Institute of Scientific and Technical Information of China (English)

    彭向东; 刘张; 陈虹; 康晶晶; 季金萍

    2012-01-01

    目的:探讨注意缺陷多动障碍(ADHD)儿童体内IL-1β、IL-6、TNF-α含量变化及可能的发病机制;分析IL-1β、IL-6、TNF-α与ADHD症状特征及行为问题的关系.方法:对35例符合DSM-Ⅳ诊断标准的ADHD和25例正常儿童进行血清IL-1β、IL-6、TNF-α浓度测定,选用Achenbach儿童行为量表(CBCL)进行行为评定,比较两组IL-1β、1L-6、TNF-α浓度水平,并与DSM-Ⅳ诊断标准和CBCL得分进行相关分析.结果:ADHD儿童IL-1β较对照组增高,差异有统计学意义(x2=4.239,P=0.041;Z=2.051,P=0.040);IL-6较对照组增高,但差异不具统计学意义(x2=3.138,P=0.074;Z=1.892,P=0.058);TNF-α较对照组降低,差异有统计学意义(x2=5.173,P=0.023;Z=2.792,P=0.005);TNF-α与注意缺陷因子、多动/冲动因子负相关(r=-0.377,P=0.003;r=-0.274,P=0.034);IL-1β与注意缺陷因子正相关(r=0.273,P=0.035);TNF-α与CBCL注意问题、违纪行为、攻击行为、外向性、行为问题总分负相关(r=-0.325,P=0.011;r=-0.396,P=0.002;r=-0.306,P=0.017;r=-0.324,P=0.011;r=-0.346,P=0.007).结论:ADHD儿童存在高水平的IL-1β和低水平的TNF-α;IL-1β尤其是TNF-α与ADHD注意缺陷症状及某些行为问题间存在关联性.%Objective; To explore the changes of interleukin - lβ (IL-1β), interleukin -6 (IL -6), and tumor necrosis factor - α (TNF - α) contents in the children with attention deficit hyperactivity disorder ( ADHD) and the possible pathogenesis, analyze the relationship between IL - 1 β, IL - 6, TNF - a and symptom characteristics, behavior problems of ADHD. Methods; The serum contents of IL -lp, IL-6, and TNF-a in 35 children meeting the diagnostic criteria of DSM - IV and 25 normal children were detected, Achenbach child behavior checklist (CBCL) was used for behavior evaluation; the serum contents of IL - 1 β, IL - 6, and TNF - α in the two groups were compared; correlation analysis was conducted on serum contents of IL - 1 β, IL - 6, TNF - α and

  12. Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

    Science.gov (United States)

    Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke; Solomon, Thomas P J; Lehrskov-Schmidt, Lars; Holst, Jens Juul; Møller, Kirsten

    2013-11-01

    Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown. We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated. TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged. In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect. Copyright © 2013 John Wiley & Sons, Ltd.

  13. SERUM YKL-40 CORRELATES WITH SERUM INTERLEUKIN-6 IN MULTIPLE MYELOMA

    DEFF Research Database (Denmark)

    Mylin, Anne Kjærsgaard; Andersen, Niels Frost; Johansen, Julia S.

    2007-01-01

    identified using immunohistochemical staining for CD34-positive endothelial cells. The serum concentrations of the angiogenic cytokines interleukin-6 (S-IL-6), hepatocyte growth factor (S-HGF) and basic fibroblast growth factor (S-bFGF) were measured in both peripheral blood (PB) and BM. Results. 57...... compared to patients with normal S-YKL-40 although the difference was only significant for IL-6. At the same time, a negative association between S-YKL-40 level and BM levels of bFGF was seen (Table 1). The association between S-YKL-40 and S-IL-6 was further anlysed using S-YKL-40 as a continuous variable...... showing a strong correlation with S-IL-6 in both BM (rho = 0.51; p=0.03) and PB (rho = 0.60; pS-IL-6 not differing between BM and PB in the individual patient. Conclusions. In patients with newly diagnosed MM the S-YKL-40 level lack association with the degree of BM angiogenesis...

  14. Interleukin-6 gene (IL-6: a possible role in brain morphology in the healthy adult brain

    Directory of Open Access Journals (Sweden)

    Baune Bernhard T

    2012-07-01

    Full Text Available Abstract Background Cytokines such as interleukin 6 (IL-6 have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology In a large sample of healthy individuals (N = 303, associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840 and brain volume (gray matter volume were analyzed using voxel-based morphometry (VBM. Selection of single nucleotide polymorphisms (SNPs followed a tagging SNP approach (e.g., Stampa algorigthm, yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286 = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577 within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress are warranted.

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

    Science.gov (United States)

    Hamid, Yasmin H; Urhammer, Søren A; Jensen, Dorit P; Glümer, Charlotte; Borch-Johnsen, Knut; Jørgensen, Torben; Hansen, Torben; Pedersen, Oluf

    2004-12-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the pathophysiology of various human diseases such as type 2 diabetes and obesity. IL-6 signals via a heterodimeric receptor complex consisting of a soluble IL-6 alpha-subunit (IL-6 receptor [IL6R]) and a signal transducing subunit (gp130). The IL6R gene maps to an important candidate locus for type 2 diabetes on chromosome 1q21. An Asp358Ala polymorphism of the IL6R has been reported to associate with obesity in Pima Indians. We investigated the Asp358Ala polymorphism in relation to type 2 diabetes, obesity, and other pre-diabetic quantitative traits among Danish whites. By applying a recessive genetic model in a case-control study of 1,349 type 2 diabetic patients and 4,596 glucose-tolerant control subjects, we found a significant difference in genotype distribution (P = 0.008) and in allele frequency (Ala-allele 38.3% [95% CI 36.5-40.1] in diabetic subjects vs. 41.2% [40.2-42.2] in control subjects; P = 0.007). The odds ratio for the Asp/Asp carriers versus Ala/Ala carriers was 1.38 (1.09-1.71). Among 4,251 middle-aged glucose-tolerant subjects, the Asp358Ala polymorphism was not associated with estimates of obesity, post-oral glucose tolerance test serum insulin release, or the homeostasis model assessment of insulin resistance index. In conclusion, the Asp358Ala polymorphism of the IL6R associates with type 2 diabetes in Danish whites.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    to Control. Plasma 8-iso-prostaglandin F(2alpha), a marker of lipid peroxidation, increased in response to exercise in Control, but not in Treatment. In both Control and Treatment, skeletal muscle IL-6 mRNA and protein levels increased between 0 and 3 h. In contrast, the net release of IL-6 from the leg......Contracting human skeletal muscle is a major contributor to the exercise-induced increase of plasma interleukin-6 (IL-6). Although antioxidants have been shown to attenuate the exercise-induced increase of plasma IL-6, it is unknown whether antioxidants inhibit transcription, translation...... (6 h). Leg blood flow was measured using Doppler ultrasonography. Plasma IL-6 concentration was measured in blood sampled from the femoral artery and vein. The net release of IL-6 was calculated using Fick's principle. Plasma vitamin C and E concentrations were elevated in Treatment compared...

  17. Transsignaling of Interleukin-6 Crucially Contributes to Atherosclerosis in Mice

    NARCIS (Netherlands)

    Schuett, Harald; Oestreich, Rene; Waetzig, Georg H.; Annema, Wijtske; Luchtefeld, Maren; Hillmer, Anja; Bavendiek, Udo; von Felden, Johann; Divchev, Dimitar; Kempf, Tibor; Wollert, Kai C.; Seegert, Dirk; Rose-John, Stefan; Tietge, Uwe J. F.; Schieffer, Bernhard; Grote, Karsten

    2012-01-01

    Objective-Transsignaling of interleukin (IL)-6 is a central pathway in the pathogenesis of disorders associated with chronic inflammation, such as Crohn disease, rheumatoid arthritis, and inflammatory colon cancer. Notably, IL-6 also represents an independent risk factor for coronary artery disease

  18. The Effect of Air Tourniquet on Interleukin-6 Levels in Total Knee Arthroplasty

    Science.gov (United States)

    Tsunoda, Kenji; Sonohata, Motoki; Kugisaki, Hajime; Someya, Shinsuke; Honke, Hidefumi; Komine, Mitsunori; Izumi, Masataka; Ide, Shuya; Mawatari, Masaaki

    2017-01-01

    Background: Air tourniquet-induced skeletal muscle injury increases the concentrations of some cytokines such as interleukin-6 (IL-6) in plasma. However, the effect of an air tourniquet on the IL-6 concentrations after total knee arthroplasty (TKA) is unclear. We therefore investigated the impact of tourniquet-induced ischemia and reperfusion injury in TKA using the IL-6 level as an index. Methods: Ten patients with primary knee osteoarthrosis who underwent unilateral TKA without an air tourniquet were recruited (Non-tourniquet group). We also selected 10 age- and sex-matched control patients who underwent unilateral TKA with an air tourniquet (Tourniquet group). Venous blood samples were obtained at 3 points; before surgery, 24 h after surgery, and 7 days after surgery. The following factors were compared between the two groups; IL-6, C-reactive protein (CRP), creatine phosphokinase (CPK), the mean white blood cell (WBC) counts, and the maximum daily body temperatures. Results: The IL-6 level at 24 h after surgery was significantly higher than that at any other point (p<0.01). No significant differences were observed in the WBC count, the body temperature, or the CRP, CPK, or IL-6 levels of the two groups at any of the time points. Conclusion: The effect of ischemia and reperfusion due to the use of an air tourniquet on increasing the IL-6 level was much smaller than that induced by surgical stress in TKA. PMID:28217217

  19. Interleukin-1 beta, interleukin-6 and TGF-beta in follicular tissue of impacted third molars.

    Science.gov (United States)

    Mesgarzadeh, Ali Hossein; Abolfathi, Ali Akbar; Dastgiri, Saeed; Shaaker, Maghsod; Vatankhah, Amir Mansour; Solehakahnamoiee, Shiva; Darabi, Masoud

    2011-06-01

    The clinical evaluation and management of impacted third molars remain challenging. The aim of the present study was to investigate possible associations between follicular tissue cytokines and radiographic manifestations of impacted third molar. The population included 72 patients who underwent surgical extraction of impacted third molars. All these patients underwent a preliminary panoramic radiograph. Levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and transforming growth factor beta (TGF-β) in tissue extracts were determined using ELISA. There were no significant differences between bony and tissue impaction as regards IL-1β, IL-6 and TGF-β levels. Moreover, the same results were obtained as far as the amount of pericoronal space and the presence or absence of a history of pericoronitis are concerned. These results suggest that radiographic findings or a history of pericoronitis are not associated with levels of expression of pro-inflammatory cytokines in patients undergoing surgical removal of impacted third molars. However, further studies are needed to address the possibility of variability during disease progression.

  20. Preclinical validation of interleukin 6 as a therapeutic target in multiple myeloma

    Science.gov (United States)

    Rosean, Timothy R.; Tompkins, Van S.; Tricot, Guido; Holman, Carol J.; Olivier, Alicia K.; Zhan, Fenghuang; Janz, Siegfried

    2014-01-01

    Studies on the biologic and molecular genetic underpinnings of multiple myeloma (MM) have identified the pleiotropic, pro-inflammatory cytokine, interleukin-6 (IL-6), as a factor crucial to the growth, proliferation and survival of myeloma cells. IL-6 is also a potent stimulator of osteoclastogenesis and a sculptor of the tumor microenvironment in the bone marrow of patients with myeloma. This knowledge has engendered considerable interest in targeting IL-6 for therapeutic purposes, using a variety of antibody- and small-molecule-based therapies. However, despite the early recognition of the importance of IL-6 for myeloma and the steady progress in our knowledge of IL-6 in normal and malignant development of plasma cells, additional efforts will be required to translate the promise of IL-6 as a target for new myeloma therapies into significant clinical benefits for patients with myeloma. This review summarizes published research on the role of IL-6 in myeloma development and describes ongoing efforts by the University of Iowa Myeloma Multidisciplinary Oncology Group to develop new approaches to the design and testing of IL-6-targeted therapies and preventions of MM. PMID:24845460

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S...... patients an increase (mean 7.7%) in LI of mononuclear bone marrow cells during the rhIL-6 treatment was demonstrated and in one patient a decrease of 2.8% was seen. Assessment of PCLI demonstrated an increase of 2.9% in one out of six patients and a decrease of 1.9% in one out of six patients. None...... of the 15 patients achieved remission according to standard criteria. During the rhIL-6 treatment, 14 of the 15 patients developed mild constitutional adverse events (AE) well known in patients treated with IL-6, and none of the AE in the subsequent chemotherapy phase were related to IL-6. In conclusion...

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

    Directory of Open Access Journals (Sweden)

    Anitha Balaji

    2017-01-01

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

  3. Genetic polymorphisms of interleukin 6 and interleukin 10 in Egyptian patients with systemic lupus eythematosus.

    Science.gov (United States)

    Talaat, R M; Alrefaey, S A; Bassyouni, I H; Ashour, M E; Raouf, A A

    2016-03-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Cytokine gene polymorphisms play an important role in SLE. Thus, this study aimed to investigate the associations between interleukin 6 (IL-6) and interleukin 10 (IL-10) promoter single-nucleotide polymorphisms (SNPs) and their susceptibility to SLE and the implications for plasma levels. We genotyped IL-6-174G/C (rs1800795) using mutagenically separated polymerase chain reaction (MS-PCR) and IL-10-1082G/A (rs1800896) and -819C/T (rs1800871) using sequence specific primer polymerase chain reaction (SSP-PCR) in 100 Egyptian patients and 119 controls. The plasma levels of IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). There was significant increase in the frequency of IL-6 (-174) GG genotype (P IL-10 (-1082G/A) GG (P IL-10 (P IL-10 gene polymorphisms in SLE patients. In conclusion, our preliminary study indicated that both GG genotype and G allele of IL-6 (-174G/C) could be considered as risk factors for SLE. In addition, the polymorphisms at IL-10 (-1082 G/G and AA) may play a role in SLE susceptibility in Egyptian patients. Larger prospective studies are needed to confirm our findings.

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

    DEFF Research Database (Denmark)

    Christ, Bruno; Yazici, Emine; Nath, Annegret

    2000-01-01

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

  5. Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

    LENUS (Irish Health Repository)

    Dowdall, J F

    2012-02-03

    The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

  6. Reduction of Burn Progression with Topical Delivery of (Antitumor Necrosis Factor-alpha )-Hyaluronic Acid Conjugates

    Science.gov (United States)

    2012-01-01

    level of hair follicle cell apoptosis within 24 hours of the initial burn injury.27 Intravenous injection of semapimod, a selective inhibitor of...effect of such treat- ment was unclear. Singer and coworkers have also demonstrated 30% reduction in depth of hair follicle necrosis after systemic...whether topical application of antibodies targeting tumor necrosis factor-a (TNF-a) or interleukin-6 (IL-6) conjugated to hyaluronic acid (HA) could

  7. Tumor necrosis factor-alpha increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: a potential mechanism for inflammation-induced carcinogenesis.

    Science.gov (United States)

    Babbar, Naveen; Casero, Robert A

    2006-12-01

    Inflammation has been implicated in the development of many human epithelial cancers, including those of the stomach, lung, colon, and prostate. Tumor necrosis factor-alpha (TNF-alpha) is a potent pleiotropic, proinflammatory cytokine produced by many cells in response to injury and inflammation. Here, we show that TNF-alpha exposure results in increased production of reactive oxygen species (ROS), with a concomitant increase in the production of 8-oxo-deoxyguanosine, a marker for oxidative DNA damage, in human lung bronchial epithelial cells. The source of the ROS in TNF-alpha-treated cells was determined by both pharmacologic and small interfering RNA (siRNA) strategies to be spermine oxidase (SMO/PAOh1). SMO/PAOh1 oxidizes spermine into spermidine, 3-aminopropanal, and H(2)O(2). Inhibition of TNF-alpha-induced SMO/PAOh1 activity with MDL 72,527 or with a targeted siRNA prevented ROS production and oxidative DNA damage. Further, similar induction in SMO/PAOh1 is observed with treatment of another inflammatory cytokine, interleukin-6. The data are consistent with a model that directly links inflammation and DNA damage through the production of H(2)O(2) by SMO/PAOh1. Further, these results suggest a common mechanism by which inflammation from multiple sources can lead to the mutagenic changes necessary for the development and progression of epithelial cancers.

  8. Pathological Role of Interleukin-6 in Psoriatic Arthritis

    Directory of Open Access Journals (Sweden)

    Atsushi Ogata

    2012-01-01

    Full Text Available Psoriatic arthritis (PsA is a clinical manifestation of psoriatic disease. Although the pathogenesis of PsA remains unknown, PsA can be managed by treatments similar to those used for rheumatoid arthritis (RA. Because interleukin-(IL- 6 has been suggested to have a pathogenic role in PsA, a humanized anti-IL-6 receptor antibody tocilizumab treatment for PsA was recently tried. However, the efficacy of tocilizumab for PsA was not favorable. This suggests that the pathogenic roles of IL-6 in PsA and RA are different. In RA, tumor necrosis factor (TNF primarily contributes to the arthritis effector phase and IL-6 contributes to the arthritis priming phase. In PsA, the TNF-related effector phase is similar to that in RA, but the IL-6-related priming phase might not be critical. This paper discusses the role of IL-6 in PsA.

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

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T; Carrasco, J;

    1999-01-01

    Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory...... response in the brain following disruption of the blood-brain barrier (BBB), we examined the effects of a focal cryo injury to the fronto-parietal cortex in interleukin-6-deficient (IL-6-/-) and normal (IL-6+/+) mice. In IL-6+/+ mice, brain injury resulted in the appearance of brain macrophages...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-17

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

  11. The effect of sunlight exposure on interleukin-6 levels in depressive and non-depressive subjects.

    Science.gov (United States)

    Levandovski, Rosa; Pfaffenseller, Bianca; Carissimi, Alicia; Gama, Clarissa S; Hidalgo, Maria Paz Loayza

    2013-03-05

    The objective of this epidemiological study was to evaluate the effect of length of sunlight exposure on interleukin 6 (IL-6) levels in depressive and non-depressive subjects. This was a cross-sectional study with 154 subjects (54 males, mean age: 43.5 ± 12.8 years) who were living in a rural area in south Brazil. Chronobiological and light parameters were assessed using the Munich Chronotype Questionnaire. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index. Depressive symptoms were assessed with the Beck Depression Inventory. Plasma levels of inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, and interferon) were collected during the daytime and measured. IL-6 levels showed a positive correlation with light exposure (r = 0.257; p exposure was an independent factor for predicting IL-6 levels (ß = 0.26; p = 0.002). In non-depressed subjects, exposure to a different intensity of light did not affect IL-6 levels (t = -1.6; p = 0.1). However, when the two depressive groups with low and high light exposure were compared, the low light exposure group had lower levels of IL-6 compared with the high light exposure group (t = -2.19 and p = 0.0037). The amount of time that participants are exposed to sunlight is directly related to their IL-6 levels. Additionally, depressed subjects differ in their IL-6 levels if they are exposed to light for differing amounts of time.

  12. A ribonucleoprotein complex protects the interleukin-6 mRNA from degradation by distinct herpesviral endonucleases.

    Directory of Open Access Journals (Sweden)

    Mandy Muller

    2015-05-01

    Full Text Available During lytic Kaposi's sarcoma-associated herpesvirus (KSHV infection, the viral endonuclease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA. However, select mRNAs escape SOX-induced cleavage and remain robustly expressed. Prominent among these is interleukin-6 (IL-6, a growth factor important for survival of KSHV infected B cells. IL-6 escape is notable because it contains a sequence within its 3' untranslated region (UTR that can confer protection when transferred to a SOX-targeted mRNA, and thus overrides the endonuclease targeting mechanism. Here, we pursued how this protective RNA element functions to maintain mRNA stability. Using affinity purification and mass spectrometry, we identified a set of proteins that associate specifically with the protective element. Although multiple proteins contributed to the escape mechanism, depletion of nucleolin (NCL most severely impacted protection. NCL was re-localized out of the nucleolus during lytic KSHV infection, and its presence in the cytoplasm was required for protection. After loading onto the IL-6 3' UTR, NCL differentially bound to the translation initiation factor eIF4H. Disrupting this interaction, or depleting eIF4H, reinstated SOX targeting of the RNA, suggesting that interactions between proteins bound to distant regions of the mRNA are important for escape. Finally, we found that the IL-6 3' UTR was also protected against mRNA degradation by the vhs endonuclease encoded by herpes simplex virus, despite the fact that its mechanism of mRNA targeting is distinct from SOX. These findings highlight how a multitude of RNA-protein interactions can impact endonuclease targeting, and identify new features underlying the regulation of the IL-6 mRNA.

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

    Directory of Open Access Journals (Sweden)

    Masahiko Mihara

    2011-02-01

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

  14. Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer.

    Science.gov (United States)

    Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; García-Rivello, Hernán; Wernicke, Alejandra; Feldman, Leonardo; Giorello, María Belén; Matas, Ayelén; Borzone, Francisco Raúl; Howard, Scott C; Chasseing, Norma Alejandra

    2016-10-01

    Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Vozarova, B; Weyer, C; Hanson, K;

    2001-01-01

    Plasma concentrations of interleukin-6 (IL-6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined...

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

    DEFF Research Database (Denmark)

    Lyngsø, Dorthe; Simonsen, Lene; Bülow, Jens

    2002-01-01

    Interleukin-6 (IL-6) was infused intravenously for 2.5 h in seven healthy human volunteers at a dose giving rise to a circulating IL-6 concentration of approximately 35 ng l(-1). The metabolic effects of this infusion were studied in subcutaneous adipose tissue on the anterior abdominal wall and ...

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

  2. Recombinant human interleukin 6 in metastatic renal cell cancer : A phase II trial

    NARCIS (Netherlands)

    Stouthard, JML; Goey, H; deVries, EGE; deMulder, PH; Groenewegen, A; Stoter, G; Sauerwein, HP; Bakker, PJM; Veenhof, CHN

    A phase II trial investigating the anti-tumour effects of recombinant human interleukin 6 (rhlL-6) in patients with metastatic renal cell cancer was carried out. RhIL-6 (150 mu g) was administered as a daily subcutaneous injection for 42 consecutive days on an outpatient basis. Forty-nine patients

  3. Effect of exercise modality and intensity on post-exercise interleukin-6 and hepcidin levels

    NARCIS (Netherlands)

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

    2013-01-01

    The effect of exercise modality and intensity on Interleukin-6 (IL-6), iron status, and hepcidin levels was investigated. Ten trained male triathletes performed 4 exercise trials including low-intensity continuous running (L-R), low-intensity continuous cycling (L-C), high-intensity interval running

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

    NARCIS (Netherlands)

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

    1995-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  7. Effect of exercise modality and intensity on post-exercise interleukin-6 and hepcidin levels

    NARCIS (Netherlands)

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

    2013-01-01

    The effect of exercise modality and intensity on Interleukin-6 (IL-6), iron status, and hepcidin levels was investigated. Ten trained male triathletes performed 4 exercise trials including low-intensity continuous running (L-R), low-intensity continuous cycling (L-C), high-intensity interval running

  8. Recombinant human interleukin 6 in metastatic renal cell cancer : A phase II trial

    NARCIS (Netherlands)

    Stouthard, JML; Goey, H; deVries, EGE; deMulder, PH; Groenewegen, A; Stoter, G; Sauerwein, HP; Bakker, PJM; Veenhof, CHN

    1996-01-01

    A phase II trial investigating the anti-tumour effects of recombinant human interleukin 6 (rhlL-6) in patients with metastatic renal cell cancer was carried out. RhIL-6 (150 mu g) was administered as a daily subcutaneous injection for 42 consecutive days on an outpatient basis. Forty-nine patients w

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  10. Transforming growth factor (TGF)-. alpha. in human milk

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Masaki; Wakai, Kae; Shizume, Kazuo (Research Institute for Growth Sciences, Tokyo (Japan)); Iwashita, Mitsutoshi (Tokyo Women' s Medical College (Japan)); Ohmura, Eiji; Kamiya, Yoshinobu; Murakami, Hitomi; Onoda, Noritaka; Tsushima, Toshio

    1991-01-01

    Transforming growth factor (TGF)-{alpha} and epidermal growth factor (EGF) were measured in human milk by means of homologous radioimmunoassay. As previously reported, EGF concentration in the colostrum was approximately 200 ng/ml and decreased to 50 ng/ml by day 7 postpartum. The value of immunoreactive (IR)-TGF-{alpha} was 2.2-7.2 ng/ml, much lower than that of EGF. In contrast to EGF, the concentration of IR-TGF-{alpha} was fairly stable during the 7 postpartum days. There was no relationship between the concentrations of IR-TGF-{alpha} and IR-EGF, suggesting that the regulatory mechanism in the release of the two growth factors is different. On gel-chromatography using a Sephadex G-50 column, IR-EGF appeared in the fraction corresponding to that of authentic human EGF, while 70%-80% of the IR-TGF-{alpha} was eluted as a species with a molecular weight greater than that of authentic human TGF-{alpha}. Although the physiological role of TGF-{alpha} in milk is not known, it is possible that it is involved in the development of the mammary gland and/or the growth of newborn infants.

  11. Association of interleukin-6 promoter polymorphism with knee osteoarthritis: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Ai Zhipeng; Ning Xianming; Shou Tao; Tang Wenru; Luo Ying; Zhang Jihong

    2014-01-01

    Background Osteoarthritis (OA) is the most common form of human polyarthritis.Many genetic factors have been implicated in OA.It was reported that a polymorphism in the gene of interleukin-6 (IL-6) was associated with OA of knee.The aim of this study was to determine whether functional IL-6 promoter-174G/C (rs1800795) polymorphisms confer susceptibility to knee OA.Methods A meta-analysis was conducted on the association between the IL-6 polymorphism and knee OA.Electronic search at PubMed,EMBASE,Weipu database,and Wanfang database was conducted to select studies.Case-control studies containing available genotype frequencies of IL-6-174G/C were chosen,and odds ratio (OR) with 95% confidence interval (C/) was used to assess the strength of this association.Results A total of seven studies involving 6 464 subjects (knee OA 3 331 and controls 3 133) were considered in this study.The results suggested that the variant genotypes were not associated with knee OA risk in all genetic models (additive model:OR=1.144,95% CI 0.934-1.402,P=0.194; recessive model:OR=1.113,95% CI 0.799-1.550,P=0.526;dominant model:OR=1.186,95% CI 0.918-1.531,P=0.191).A symmetric funnel plot,the Begg's test (P >0.05),suggested that the data lacked publication bias.Conclusions This meta-analysis does not support the idea that rs1800795 genotype is associated with increased risk of knee OA.However,to draw comprehensive and more reliable conclusions,further prospective studies with larger numbers of participants worldwide are needed to examine the association between rs1800795 polymorphism and knee OA.

  12. Peripheral and central blockade of interleukin-6 trans-signaling differentially affects sleep architecture.

    Science.gov (United States)

    Oyanedel, Carlos N; Kelemen, Eduard; Scheller, Jürgen; Born, Jan; Rose-John, Stefan

    2015-11-01

    The immune system is known to essentially contribute to the regulation of sleep. Whereas research in this regard focused on the pro-inflammatory cytokines interleukin-1 and tumor necrosis factor, the role of interleukin-6 (IL-6) in sleep regulation has been less intensely studied, probably due to the so far seemingly ambiguous results. Yet, this picture might simply reflect that the effects of IL-6 are conveyed via two different pathways (with possibly different actions), i.e., in addition to the 'classical' signaling pathway via the membrane bound IL-6 receptor (IL-6R), IL-6 stimulates cells through the alternative 'trans-signaling' pathway via the soluble IL-6R. Here, we concentrated on the contributions of the trans-signaling pathway to sleep regulation. To characterize this contribution, we compared the effect of blocking IL-6 trans-signaling (by the soluble gp130Fc fusion protein) in the brain versus body periphery. Thus, we compared sleep in transgenic mice expressing the soluble gp130Fc protein only in the brain (GFAP mice) or in the body periphery (PEPCK mice), and in wild type mice (WT) during a 24-h period of undisturbed conditions and during 18 h following a 6-h period of sleep deprivation. Compared with WT mice, PEPCK mice displayed less sleep, particularly during the late light phase, and this was accompanied by decreases in slow wave sleep (SWS) and rapid eye movement (REM) sleep. Following sleep deprivation PEPCK mice primarily recovered REM sleep rather than SWS. GFAP mice showed a slight decrease in REM sleep in combination with a profound and persistent increase in EEG theta activity. In conclusion, peripheral and central nervous IL-6 trans-signaling differentially influences brain activity. Peripheral IL-6 trans-signaling appears to more profoundly contribute to sleep regulation, mainly by supporting SWS.

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

    Directory of Open Access Journals (Sweden)

    Hiroto Kinoshita

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

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

    Science.gov (United States)

    de Nully Brown, P; Jensen, P O; Diamant, M; Mortensen, B T; Hovgaard, D; Gimsing, P; Nissen, N I

    1998-11-01

    The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S-phase proportion of myeloma cells, which might increase the sensitivity to chemotherapy, we gave rhIL-6 followed by chemotherapy to 15 myeloma patients with refractory disease. A total of 25 treatment cycles were administered since ten patients had two cycles. The rhIL-6 dose was 2.5 (n = 3), 5.0 (n = 6) and 10.0 microg/kg (n = 6) by subcutaneous injection once daily for 5 days and chemotherapy was administered on the last day of rhIL-6 injection. The effect of rhIL-6 treatment on labeling index (LI) was heterogeneous, but no statistically significant change was noted for this particular group as a whole. In two patients an increase (mean 7.7%) in LI of mononuclear bone marrow cells during the rhIL-6 treatment was demonstrated and in one patient a decrease of 2.8% was seen. Assessment of PCLI demonstrated an increase of 2.9% in one out of six patients and a decrease of 1.9% in one out of six patients. None of the 15 patients achieved remission according to standard criteria. During the rhIL-6 treatment, 14 of the 15 patients developed mild constitutional adverse events (AE) well known in patients treated with IL-6, and none of the AE in the subsequent chemotherapy phase were related to IL-6. In conclusion, our study demonstrated that rhIL-6 can be administered safely to patients with refractory MM, but the cell cycle recruitment approach was not sufficiently effective to be of clinical value.

  15. Interleukin-6 promoter haplotypes are associated with etanercept response in patients with rheumatoid arthritis.

    Science.gov (United States)

    Schotte, Heiko; Schmidt, Hartmut; Gaubitz, Markus; Drynda, Susanne; Kekow, Jörn; Willeke, Peter; Schlüter, Bernhard

    2015-12-01

    Indices prognosticating anti-tumor necrosis factor (TNF) response in patients with rheumatoid arthritis are a matter of interest. Differential outcome under anti-TNF and anti-interleukin-6 (IL-6) therapy raises the question whether genetic polymorphisms that have previously been linked to IL-6 production are associated with response to anti-TNF therapy. Fifty (50) rheumatoid arthritis (RA) patients were treated with etanercept (median 36 weeks, range 4-52). In terms of the EULAR response criteria, 25 patients responded well, 17 patients moderately and 8 patients not. By direct sequencing, the patients and 91 matched healthy controls were genotyped for the IL-6 promoter SNPs -597G > A (rs1800797), -572G > C (rs1800796) and -174G > C (rs1800795) and for an AnTn microsatellite tract at -373. Alleles and haplotypes were tested for association with disease susceptibility and therapy response. No significant difference was seen in the genotype distribution between patients and healthy controls. Confirming the results of previous studies, we observed a trend of -174G being more frequent in patients with a good or moderate therapy response. Beyond that, carriage of the A9T11 microsatellite allele within the -174G haplotype was associated most closely with a favourable response (relative risk 1.31; 95 % confidence interval 1.02-1.68). A subtle analysis of the IL-6 promoter giving respect to its complex haplotypic structure results in more precise information as to the association of genotypes with the long-term etanercept response. Despite a conclusive hypothesis that a genetically determined IL-6-dominated RA responds less well to anti-TNF, more work has to be done to provide us with reliable information regarding the functional aspects of these genetic polymorphisms.

  16. Interleukin-6 (IL-6) haplotypes and the response to therapy of chronic hepatitis C virus infection

    Science.gov (United States)

    Yee, Leland J.; Im, KyungAh; Borg, Brian; Yang, Huiying; Liang, T. Jake

    2009-01-01

    Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-α-2a is successful in eradicating virus from only 30%–80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained viral response (SVR) to therapy for chronic HCV infection. We observed the IL-6 T-T-G-G-G-G-C-A-G-A haplotype to be associated with a lower risk of achieving SVR among Caucasian Americans (CAs) (RR=0.80; 95%C.I.: 0.66– 0.98; p=0.0261). Using a sliding window approach, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was associated with a reduced chance of SVR (RR=0.79; 95%C.I.: 0.66–0.94; p=0.0081), as was the rs1800796-(G)-rs1800795-(G)-rs2069830-(C) haplotype (RR=0.78; 95%C.I.: 0.66–0.94; p=0.0065) among CAs. Overall, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was independently associated with a reduced chance of SVR (RR=0.78; 95% C.I.: 0.62–1.0; p=0.0489) after adjustment for potential confounding factors. Our findings further illustrate the complexity of IL-6 genetic regulation and the potential importance of haplotypes on IL-6 expression. Our findings provide additional support for the potential importance of genetic variation in the IL-6 gene and the response to HCV therapy. PMID:19387461

  17. Postoperative Interleukin-6 Level and Early Detection of Complications After Elective Major Abdominal Surgery.

    Science.gov (United States)

    Rettig, Thijs C D; Verwijmeren, Lisa; Dijkstra, Ineke M; Boerma, Djamila; van de Garde, Ewoudt M W; Noordzij, Peter G

    2016-06-01

    To assess the association of systemic inflammation and outcome after major abdominal surgery. Major abdominal surgery carries a high postoperative morbidity and mortality rate. Studies suggest that inflammation is associated with unfavorable outcome. Levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α and the systemic inflammatory response syndrome (SIRS) were assessed in 137 patients undergoing major abdominal surgery. Blood samples were drawn on days 0, 1, 3, and 7, and SIRS was scored during 48 hours after surgery. Primary outcome was a composite of mortality, pneumonia, sepsis, anastomotic dehiscence, wound infection, noncardiac respiratory failure, atrial fibrillation, congestive heart failure, myocardial infarction, and reoperation within 30 days of surgery. An IL-6 level more than 432 pg/mL on day 1 was associated with an increased risk of complications (adjusted odds ratio: 3.3; 95% confidence interval [CI]: 1.3-8.5) and a longer median length of hospital stay (7 vs 12 days, P < 0.001). As a single test, an IL-6 cut-off level of 432 pg/mL on day 1 yielded a specificity of 70% and a sensitivity of 64% for the prediction of complications (area under the curve: 0.67; 95% CI: 0.56-0.77). Levels of CRP started to discriminate from day 3 onward with a specificity of 87% and a sensitivity of 58% for a cut-off level of 203 mg/L (AUC: 0.73; 95% CI: 0.63-0.83). A high IL-6 level on day 1 is associated with postoperative complications. Levels of IL-6 help distinguish between patients at low and high risk for complications before changes in levels of CRP.

  18. The Study of Serum Interleukin-6 and Vascular Endothelial Growth Factor Level in Patients with Obstructive Sleep Apnea Hypopnea Syndrome Associated Hypertension%阻塞性睡眠呼吸暂停低通气综合征合并高血压患者血清白细胞介素-6和血管内皮生长因子水平的研究

    Institute of Scientific and Technical Information of China (English)

    云春梅; 赵小娟; 李晓玲

    2011-01-01

    Objective:To investigate the role of interleukin-6(IL-6) .vascular endothelial growth factor(VEGF) in the patho-genesis of obstructive sleep apnea hyponea syndrome (OSAHS) and obstructive sleep apnea hyponea associated hypertension (OSAHAHT). Methods-. A total of 30 OSAHS cases,24 OSAHAHT cases and 30 healthy control cases were enrolled . The serum levels of IL-6 and VEGF were measured . Polysomnography (PSG) were used in all participants. Results: (1) Apnea hypopnea index( AHI) and TST-SP<90% of patients with OSAHAHT were significantly higher than those with OSAHS, but MaO2 ,LaO2 were significantly lower. There were no significant difference between the two groups'LAT. (2) The serum levels of IL-6 and VEGF in patients with OSAHAHT were significantly higher than those of OSAHS cases . Compared with healthy control group,both the two groups had significant difference . (3) Both of the serum IL-6 and VEGF level were positively correlated with AHI. There was positive correlation between the serum IL-6 level and TST-SP<90%, negative correlation between VEGF and MaO2. (4) There was positive correlation between the serum IL-6 and VEGF level. Conclusions: IL-6 and VEGF probably took part in the progress of OSAHS commonly and accelerated the occurrence and development of hypertension.%目的:探讨阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hyponea syndrome,OSAHS)及OSAHS合并高血压(obstructive sleep apnea hyponea associated hypertension,OSAHAHT)患者血清白细胞介素-6(interleukin-6,IL-6)、血管内皮生长因子(vascular endothelial growth factor,VEGF)水平的变化及其临床意义.方法:选健康对照组30例、OSAHS 30例,OSAHAST 24例,用酶联免疫法(ELISA)测定血清VEGF、IL-6含量.所有患者采用多导睡眠图(polysomnography,PSG)监测.结果:(1)睡眠呼吸紊乱指数(apnea hypopnea index,AHI)、脉搏氧饱和度(SpO2)<90%时间占总睡眠时间的百分比(TST-SP<90% )OSAHAHT

  19. Influence of Sancai and conventional acupuncture manipulations on injured sciatic nerve histomorphology and serum interleukin-6 expression

    Institute of Scientific and Technical Information of China (English)

    Zedong Cheng; Songzi Wang; Wei Zhang; Chenglin Song; Yuanyuan Song; Cairong Ming; Yiguo Chen

    2010-01-01

    Acupuncture and moxibustion therapy non-specifically raises the pain threshold, relieves regional muscular tension, improves local blood circulation, accelerates elimination of algogenic substances such as acid metabolites, and promotes neural regeneration and functional rehabilitation. However, the effects of acupuncture are synthetically influenced by multiple factors, which vary with acu-puncture point, intensity, and manipulation. The present study explored the analgesic effects and mechanisms of specific Sancai acupuncture manipulation for sciatica. Results revealed that Sancai acupuncture manipulation significantly reduced inflammatory factor interleukin-6 expression in the blood serum of rats with sciatica, exhibited anti-inflammatory effects and promoted rehabilitation of injured nerves. In addition, Sancai acupuncture manipulation exhibited superior curative effects over conventional acupuncture manipulation.

  20. Assessment of urine solute and matrix effects on the performance of an enzyme-linked immunosorbent assay for measurement of interleukin-6 in dog urine

    OpenAIRE

    2011-01-01

    Measurement of cytokine concentrations within body fluids is a means of recognizing subclinical and/or unresolved, infectious and inflammatory states in patients. In the urinary tract, such information may be useful for identifying patients with pyelonephritis, asymptomatic bacteriuria, recurrent infections, and cystitis. One such cytokine, interleukin-6 (IL-6), is recognized as a primary cytokine that is produced following exposure of the urothelium to bacterial virulence factors. Complicati...

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

    DEFF Research Database (Denmark)

    Hidalgo, Juan; Florit, Sergi; Giralt, Mercedes

    2010-01-01

    Interleukin-6 (IL-6) is a major cytokine involved in both normal physiological brain functions and underlying significant neuropathology. IL-6 has been suggested to play a role in the control of body weight but the results are somewhat controversial. In this study we have challenged transgenic mi......-fat diet feeding. In summary, the present results demonstrate that brain-specific IL-6 controls body weight which may be a significant factor in physiological conditions and/or in diseases causing neuroinflammation....

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  4. Transforming growth factor alpha and epidermal growth factor in laryngeal carcinomas demonstrated by immunohistochemistry

    DEFF Research Database (Denmark)

    Christensen, M E; Therkildsen, M H; Poulsen, Steen Seier

    1993-01-01

    Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF recep...

  5. Influence of interleukin-6 and G174C polymorphism in IL-6 gene on obesity and energy balance.

    Science.gov (United States)

    Popko, Katarzyna; Gorska, E; Demkow, U

    2010-11-01

    Obesity is a multifactor disease with a very complicated etiology. Genetic factors play an important role in the development of primary obesity. They may be responsible for up to 40% of causes leading to obesity. There are a great number of genes affecting food intake and energy expenditure. Serious consequences accompanying obesity, e.g., type 2 diabetes and lipid abnormalities may be caused by increased level of proinflammatory cytokines, such as IL-1, IL-6, and TNF. It is possible that polymorphisms located in cytokine genes affect the level of protein expression. It is known that IL-6 plays a role in lipid metabolism and energy expenditure. The polymorphism found in point 174 (G174C) of a promoter region of IL-6 gene affects the level of interleukin-6 expression and, consequently, may lead to obesity and correlated conditions.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Interleukin-6 (IL-6) has been linked to a myriad of diseases associated with inflammation, including rheumatoid arthritis (RA), Crohn's disease, and several types of cancer. In 2009 the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), t......), the first humanized IL-6 receptor-inhibiting monoclonal antibody, for the treatment of RA. Although this treatment will certainly help in managing inflammatory disorders such as RA, we suggest that side effects of such blockade may be excess weight gain and hyperlipidemia.......Interleukin-6 (IL-6) has been linked to a myriad of diseases associated with inflammation, including rheumatoid arthritis (RA), Crohn's disease, and several types of cancer. In 2009 the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab...

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

    Directory of Open Access Journals (Sweden)

    Annie Kitty George

    2013-01-01

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

  8. Interleukin-6 (IL-6) haplotypes and the response to therapy of chronic hepatitis C virus infection

    OpenAIRE

    2009-01-01

    Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-α-2a is successful in eradicating virus from only 30%–80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained vir...

  9. Interleukin-6 and Interleukin-10 Gene Promoter Polymorphisms and Risk of Endemic Burkitt Lymphoma

    OpenAIRE

    Oduor, Cliff I.; Chelimo, Kiprotich; Ouma, Collins; Mulama, David H.; Foley, Joslyn; Vulule, John; Bailey, Jeffrey A.; Moormann, Ann M.

    2014-01-01

    Overexpression of interleukin-6 (IL-6) and IL-10 in endemic Burkitt lymphoma (eBL) may facilitate tumorigenesis by providing a permissive cytokine milieu. Promoter polymorphisms influence interindividual differences in cytokine production. We hypothesized that children genetically predisposed for elevated cytokine levels may be more susceptible to eBL. Using case-control samples from western Kenya consisting of 117 eBL cases and 88 ethnically matched healthy controls, we tested for the associ...

  10. Prognostic value of serum level of interleukin-6 and interleukin-8 in metastatic breast cancer patients.

    Science.gov (United States)

    Ahmed, Olal I; Adel, Azza M; Diab, Dina R; Gobran, Nagy S

    2006-01-01

    Previous studies indicated that interleukins may stimulate cancer cells growth and contribute to loco regional relapse as well as metastasis. The aim in this study was to investigate the level of interleukin-6 (IL-6) and interleukin-8 (IL-8) in metastatic breast cancer patients and find out the relation between the levels of these cytokines and the clinical out come of patients and to predict the value of these cytokines as independent prognostic factors. The present study was carried out on 40 women divided into two groups; the first group included 30 patients diagnosed as having metastatic breast cancer. The second group included 10 healthy women as controls. An immunoenzymometric assays for the quantitative measurement of human IL-6 and IL-8 were used. The serum level of IL-6 and IL-8 were measured for patients and controls. Serum level of both IL-6 and IL-8 were found to be higher in patients than in healthy volunteers. Serum IL-6 was detected in all patients and controls with a mean value of (25.3 pg/ml) versus (1.5 pg/ml) for patients and controls respectively and this difference was statistically highly significant (P IL-8 was detected in 26 patients (86.7%) and 7 controls (70%) with a mean value of (8.96 pg/ml) versus (3.9 pg/ml) for patients and controls respectively and this difference was also statistically highly significant (P IL-8 (10.2 pg/ml) in comparison with those with size less than 5cm (IL-6 14 pg/ml) and (IL-8 7.2 pg/ml) and the difference in both cases was statistically significant (P IL-8 with a mean value of 32.8 pg/ml and 10.2 pg/ml for IL-6 and IL-8 respectively, than those with less than 3 positive lymph nodes with mean value of 14 pg/ml and 6.9 pg/ml for IL-6 and IL-8 respectively and this difference was statistically significant (P IL-8 (P IL-8 was 6.2 pg/ml versus 11.3 pg/ml for patients with one metastatic site and patients with more than one metastatic site respectively. However, the level of IL-6 and IL-8 did not correlate with

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-31

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

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

    Science.gov (United States)

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

    2017-07-01

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

  13. Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers.

    Science.gov (United States)

    Sparkman, Nathan L; Buchanan, Jessica B; Heyen, Jonathan R R; Chen, Jing; Beverly, James L; Johnson, Rodney W

    2006-10-18

    Proinflammatory cytokines inhibit learning and memory but the significance of interleukin-6 (IL-6) in acute cognitive deficits induced by the peripheral innate immune system is not known. To examine the functional role of IL-6 in hippocampus-mediated cognitive impairments associated with peripheral infections, C57BL6/J (IL-6(+/+)) and IL-6 knock-out (IL-6(-/-)) mice were trained in a matching-to-place version of the water maze. After an acquisition phase, IL-6(+/+) mice injected intraperitoneally with lipopolysaccharide (LPS) exhibited deficits in working memory. However, IL-6(-/-) mice were refractory to the LPS-induced impairment in working memory. To determine the mechanism by which IL-6 deficiency conferred protection from disruption in working memory, plasma IL-1beta and tumor necrosis factor alpha (TNFalpha), c-Fos immunoreactivity in the nucleus of the solitary tract (NTS), and steady-state levels of IL-1beta and TNFalpha mRNA in neuronal layers of the hippocampus were determined in IL-6(+/+) and IL-6(-/-) mice after injection of LPS. Plasma IL-1beta and TNFalpha and c-Fos immunoreactivity in the NTS were increased similarly in IL-6(+/+) and IL-6(-/-) mice after LPS, indicating high circulating levels of IL-1beta and TNFalpha and activation of vagal afferent pathways were not sufficient to disrupt working memory in the absence of IL-6. However, the LPS-induced upregulation of IL-1beta and TNFalpha mRNA that was evident in hippocampal tissue of IL-6(+/+) mice was greatly attenuated or entirely absent in IL-6(-/-) mice. Collectively, these data suggest that humoral and neural immune-to-brain communication pathways are intact in IL-6-deficient mice but that, in the absence of IL-6, the central cytokine compartment is hyporesponsive.

  14. Influence of G308A polymorphism of tumor necrosis factor-alpha gene on inflammatory markers in postsurgical head and neck cancer patients with early enteral nutrition.

    Science.gov (United States)

    de Luis, Daniel Antonio; Sagrado, Manue Gonzalez; Vallejo, Luis Angel; Carcedo, Luis María Gil; Izaola, Olatz; Cuellar, Luis; Terroba, María Concepción; Aller, Rocío

    2007-01-01

    Although immune dysfunction in patients with cancer could be multifactorial, the immune system may be modulated by nutritional substrates and genetic background. Our study evaluated the effect of G308A polymorphism of the tumor necrosis factor-alpha (TNF-alpha) gene on inflammatory markers in patients after surgery for head and neck cancer who received early enteral nutrition. A population of 60 patients with oral and laryngeal cancer was enrolled. At surgery patients were treated with a hyperproteic enteral diet. Perioperatively and on postoperative day 6 the following parameters were evaluated: serum values of prealbumin, transferrin, total number of lymphocytes, interleukin-6, TNF-alpha, and C-reactive protein. In addition, genotyping of G308A gene polymorphism was assessed. Patients' mean age was 61.1 +/- 14.6 y (four women, 56 men) with a body mass index of 25.4 +/- 5.2 kg/m(2) and a previous weight loss of 0.35 +/- 0.2 kg. Forty patients (37 men, 3 women; 66.6%) had the genotype G308/G308 (wild group) and 20 patients (19 men, 1 woman; 23.4%) had the genotype G308/A308 (mutant group). A significant increase in prealbumin and transferrin levels was detected in both groups. C-reactive protein decreased in both groups (wild group: 105.1 +/- 60 versus 53.8 +/- 62.3 mg/dL, P < 0.05; mutant group: 99.5 +/- 46 versus 43.9 +/- 51.9 mg/dL, P < 0.05). Interleukin-6 decreased in both groups (wild group: 20.1 +/- 22 versus 6.2 +/- 4.1 pg/mL, P < 0.05; mutant group: 22.3 +/- 38 versus 9.2 +/- 7.4 pg/mL, P = NS). Lymphocytes increased in both groups (wild group: 1102 +/- 468 versus 1600 +/- 537 10(3)/mL, P = NS; mutant group: 1441 +/- 739 10(3)/mL versus 1669 +/- 614 10(6)/mL, P = NS). TNF-alpha showed no changes. The G308A polymorphism of the TNF-alpha gene did not affect levels of inflammatory markers in patients after surgery for head and neck cancer who were treated with early enteral nutrition.

  15. Phospholipase C-{delta}{sub 1} regulates interleukin-1{beta} and tumor necrosis factor-{alpha} mRNA expression

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eric; Jakinovich, Paul; Bae, Aekyung [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States); Rebecchi, Mario, E-mail: Mario.rebecchi@SBUmed.org [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States)

    2012-10-01

    Phospholipase C-{delta}{sub 1} (PLC{delta}{sub 1}) is a widely expressed highly active PLC isoform, modulated by Ca{sup 2+} that appears to operate downstream from receptor signaling and has been linked to regulation of cytokine production. Here we investigated whether PLC{delta}{sub 1} modulated expression of the pro-inflammatory cytokines interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) in rat C6 glioma cells. Expression of PLC{delta}{sub 1} was specifically suppressed by small interfering RNA (siRNA) and the effects on cytokine mRNA expression, stimulated by the Toll-like receptor (TLR) agonist, lipopolysaccharide (LPS), were examined. Real-time polymerase chain reaction (RT-PCR) results showed that PLC{delta}{sub 1} knockdown enhanced expression IL-1{beta} and tumor necrosis factor-{alpha} (TNF-{alpha}) mRNA by at least 100 fold after 4 h of LPS stimulation compared to control siRNA treatment. PLC{delta}{sub 1} knock down caused persistently high Nf{kappa}b levels at 4 h of LPS stimulation compared to control siRNA-treated cells. PLC{delta}{sub 1} knockdown was also associated with elevated nuclear levels of c-Jun after 30 min of LPS stimulation, but did not affect LPS-stimulated p38 or p42/44 MAPK phosphorylation, normally associated with TLR activation of cytokine gene expression; rather, enhanced protein kinase C (PKC) phosphorylation of cellular proteins was observed in the absence of LPS stimulation. An inhibitor of PKC, bisindolylmaleimide II (BIM), reversed phosphorylation, prevented elevation of nuclear c-Jun levels, and inhibited LPS-induced increases of IL-1{beta} and TNF-{alpha} mRNA's induced by PLC{delta}{sub 1} knockdown. Our results show that loss of PLC{delta}{sub 1} enhances PKC/c-Jun signaling and up-modulates pro-inflammatory cytokine gene transcription in concert with the TLR-stimulated p38MAPK/Nf{kappa}b pathway. Our findings are consistent with the idea that PLC{delta}{sub 1} is a

  16. Acute CSF interleukin-6 trajectories after TBI: associations with neuroinflammation, polytrauma, and outcome.

    Science.gov (United States)

    Kumar, R G; Diamond, M L; Boles, J A; Berger, R P; Tisherman, S A; Kochanek, P M; Wagner, A K

    2015-03-01

    Traumatic brain injury (TBI) results in a significant inflammatory burden that perpetuates the production of inflammatory mediators and biomarkers. Interleukin-6 (IL-6) is a pro-inflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. We hypothesized that cohort heterogeneity, temporal inflammatory profiles, and concurrent inflammatory marker associations are critical to characterize when targeting subpopulations for anti-inflammatory therapies. Toward this objective, we used serial cerebrospinal fluid (CSF) samples to generate temporal acute IL-6 trajectory (TRAJ) profiles in a prospective cohort of adults with severe TBI (n=114). We examined the impact of injury type on IL-6 profiles, and how IL-6 profiles impact sub-acute (2weeks-3months) serum inflammatory marker load and long-term global outcome 6-12months post-injury. There were two distinct acute CSF IL-6 profiles, a high and low TRAJ group. Individuals in the high TRAJ had increased odds of unfavorable Glasgow Outcome Scale (GOS) scores at 6months (adjusted OR=3.436, 95% CI: 1.259, 9.380). Individuals in the high TRAJ also had higher mean acute CSF inflammatory load compared to individuals in the low TRAJ (p⩽0.05). The two groups did not differ with respect acute serum profiles; however, individuals in the high CSF IL-6 TRAJ also had higher mean sub-acute serum IL-1β and IL-6 levels compared with the low TRAJ group (p⩽0.05). Lastly, injury type (isolated TBI vs. TBI+polytrauma) was associated with IL-6 TRAJ group (χ(2)=5.31, p=0.02). Specifically, there was 70% concordance between those with TBI+polytrauma and the low TRAJ; in contrast, isolated TBI was similarly distributed between TRAJ groups. These data provide evidence that sustained, elevated levels of CSF IL-6 are associated

  17. Associations between change in sleep duration and inflammation: findings on C-reactive protein and interleukin 6 in the Whitehall II Study.

    Science.gov (United States)

    Ferrie, Jane E; Kivimäki, Mika; Akbaraly, Tasnime N; Singh-Manoux, Archana; Miller, Michelle A; Gimeno, David; Kumari, Meena; Davey Smith, George; Shipley, Martin J

    2013-09-15

    Cross-sectional evidence suggests associations between sleep duration and levels of the inflammatory markers, C-reactive protein and interleukin-6. This longitudinal study uses data from the London-based Whitehall II study to examine whether changes in sleep duration are associated with average levels of inflammation from 2 measures 5 years apart. Sleep duration (≤5, 6, 7, 8, ≥9 hours on an average week night) was assessed in 5,003 middle-aged women and men in 1991/1994 and 1997/1999. Fasting levels of C-reactive protein and interleukin-6 were measured in 1997/1999 and 2002/2004. Cross-sectional analyses indicated that shorter sleep is associated with higher levels of inflammatory markers. Longitudinal analyses showed that each hour per night decrease in sleep duration between 1991/1994 and 1997/1999 was associated with higher levels of C-reactive protein (8.1%) and interleukin-6 (4.5%) averaged across measures in 1997/1999 and 2002/2004. Adjustment for longstanding illness and major cardiometabolic risk factors indicated that disease processes may partially underlie these associations. An increase in sleep duration was not associated with average levels of inflammatory markers. These results suggest that both short sleep and reductions in sleep are associated with average levels of inflammation over a 5-year period.

  18. Fano factor evaluation of diamond detectors for alpha particles

    Energy Technology Data Exchange (ETDEWEB)

    Shimaoka, Takehiro; Kaneko, Junichi H.; Tsubota, Masakatsu; Shimmyo, Hiroaki [Graduate School of Engineering, Hokkaido University, Kita 13, Nishi 8, Kita-ku, Sapporo, Hokkaido, 060-8628 (Japan); Sato, Yuki [Naraha Remote Technology Development Center, Japan Atomic Energy Agency, Naraha-machi, Futaba-gun, Fukushima, 979-0513 (Japan); Chayahara, Akiyoshi; Umezawa, Hitoshi; Mokuno, Yoshiaki [Advanced Power Electronics Research Center, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577 (Japan); Watanabe, Hideyuki [Research Institute for Electronics and Photonics, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, 305-8565 (Japan)

    2016-10-15

    This report is the first describing experimental evaluation of Fano factor for diamond detectors. High-quality self-standing chemical vapor deposited diamond samples were produced using lift-off method. Alpha-particle induced charge measurements were taken for three samples. A 13.1 ±0.07 eV of the average electron-hole pair creation energy and excellent energy resolution of approximately 0.3% were found for 5.486 MeV alpha particles from an {sup 241}Am radioactive source. The best Fano factor for 5.486 MeV alpha particles, calculated from experimentally obtained epsilon values and the detector intrinsic energy resolution, was 0.382 ± 0.007. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. Hypoxia inducible factor-1-alpha (HIF-1 alpha) is related to both angiogenesis and inflammation in rheumatoid arthritis

    NARCIS (Netherlands)

    Brouwer, E.; Gouw, A. S. H.; Posthumus, M. D.; van Leeuwen, M. A.; Boerboom, A. L.; Bijzet, J.; Limburg, P. C.; Kallenberg, C. G. M.; Westra, J.; Bos, R

    2009-01-01

    Objectives Despite the important role of the transcription factor HIF-1 alpha in angiogenesis and inflammation, only a few studies on HIF-1 alpha expression have been performed in RA patients. The aim of the present study was to identify the layer in synovial tissue of RA patients where HIF1 alpha i

  20. Immunoreactive transforming growth factor alpha and epidermal growth factor in oral squamous cell carcinomas

    DEFF Research Database (Denmark)

    Therkildsen, M H; Poulsen, Steen Seier; Bretlau, P

    1993-01-01

    , the cells above the basal cell layer were positive for both TGF-alpha and EGF. The same staining pattern was observed in oral mucosa obtained from healthy persons. In moderately to well differentiated carcinomas, the immunoreactivity was mainly confined to the cytologically more differentiated cells, thus......Forty oral squamous cell carcinomas have been investigated immunohistochemically for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF). The same cases were recently characterized for the expression of EGF-receptors. TGF-alpha was detected...... with a monoclonal mouse antibody and EGF with polyclonal rabbit antiserum. Thirty-five of the tumours were positive for TGF-alpha and 26 of the tumours for EGF. None of the poorly differentiated tumours was positive for EGF, but they all were for TGF-alpha. In sections including normal differentiated oral mucosa...

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

    Directory of Open Access Journals (Sweden)

    Caio Marcio Barros de Oliveira

    2015-04-01

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

  2. Expression of interleukin 6 in brain and colon of rats with TNBS-induced colitis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To characterise expression of interleukin 6(IL-6),a potent proinflammatory cytokine,in the occurrence and development of inflammatory bowel disease(IBD) and investigate its effect on neuroimmunomodulation and immune homeostasis regulation.METHODS:In this study,rats with colitis induced by trinitrobenzene sulfonic acid(TNBS) were sacrificed on days 3,7,14,21 and 28 after induction.In the controls,the TNBS was just replaced by equivalent amount of phosphate buffered solution(PBS,0.01 mol/L).IL-6 mRNA expr...

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

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Charlotte; Keller, Pernille

    2003-01-01

    Interleukin-6 (IL-6) is produced by many different cell types. Human skeletal muscles produce and release high amounts of IL-6 during exercise; however, the cell source of origin in the muscle is not known. Therefore, we studied the protein expression of IL-6 by immunohistochemistry in human muscle...... tissue from biopsies obtained at time points 0, 3, 4.5, 6, 9, and 24 h in relation to 3 h of bicycle exercise performed by healthy young males (n=12) and in resting controls (n=6). The IL-6 expression was clearly increased after exercise and remained high even by 24 h, relative to pre-exercise or resting...

  4. The Role of Interleukin-6 in Mucosal IgA Antibody Responses in Vivo

    Science.gov (United States)

    Ramsay, Alistair J.; Husband, Alan J.; Ramshaw, Ian A.; Bao, Shisan; Matthaei, Klaus I.; Koehler, Georges; Kopf, Manfred

    1994-04-01

    In mice with targeted disruption of the gene that encodes interleukin-6 (IL-6), greatly reduced numbers of immunoglobulin A (IgA)-producing cells were observed at mucosae and grossly deficient local antibody responses were recorded after mucosal challenge with either ovalbumin or vaccinia virus. The IgA response in the lungs was completely restored after intranasal infection with recombinant vaccinia viruses engineered to express IL-6. These findings demonstrate a critical role for IL-6 in vivo in the development of local IgA antibody responses and illustrate the effectiveness of vector-directed cytokine gene therapy.

  5. Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

    Institute of Scientific and Technical Information of China (English)

    Tomoyuki Okuda; Takeshi Azuma; Masahiro Ohtani; Ryuho Masaki; Yoshiyuki Ito; Yukinao Yamazaki; Shigeji Ito; Masaru Kuriyama

    2005-01-01

    AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic favors such as hypoxia-inducible factor 1 alpha (HIF-1alpha and vascular endothelial growth factor (VEGF).METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after theoccurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF.RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry.HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis.CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.

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

    DEFF Research Database (Denmark)

    Penkowa, M; Molinero, A; Carrasco, J

    2001-01-01

    , the immunoreactivity for inducible nitric oxide synthase, peroxynitrite-induced nitration of proteins and byproducts of fatty acid peroxidation were dramatically increased, as was that for metallothionein I+II, Mn-superoxide dismutase and Cu/Zn-superoxide dismutase. In accordance, a significant neuronal apoptosis...... was caused by kainic acid, as revealed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and interleukin-1beta converting enzyme/Caspase-1 stainings. In kainic acid-injected interleukin-6 null mice, reactive astrogliosis and microgliosis were reduced, while......The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice...

  7. Effects of tumor necrosis factor-alpha (TNF alpha) in epidermal keratinocytes revealed using global transcriptional profiling.

    Science.gov (United States)

    Banno, Tomohiro; Gazel, Alix; Blumenberg, Miroslav

    2004-07-30

    Identification of tumor necrosis factor-alpha (TNF alpha) as the key agent in inflammatory disorders, e.g. rheumatoid arthritis, Crohn's disease, and psoriasis, led to TNF alpha-targeting therapies, which, although avoiding many of the side-effects of previous drugs, nonetheless causes other side-effects, including secondary infections and cancer. By controlling gene expression, TNF alpha orchestrates the cutaneous responses to environmental damage and inflammation. To define TNF alpha action in epidermis, we compared the transcriptional profiles of normal human keratinocytes untreated and treated with TNF alpha for 1, 4, 24, and 48 h by using oligonucleotide microarrays. We found that TNF alpha regulates not only immune and inflammatory responses but also tissue remodeling, cell motility, cell cycle, and apoptosis. Specifically, TNF alpha regulates innate immunity and inflammation by inducing a characteristic large set of chemokines, including newly identified TNF alpha targets, that attract neutrophils, macrophages, and skin-specific memory T-cells. This implicates TNF alpha in the pathogenesis of psoriasis, fixed drug eruption, atopic and allergic contact dermatitis. TNF alpha promotes tissue repair by inducing basement membrane components and collagen-degrading proteases. Unexpectedly, TNF alpha induces actin cytoskeleton regulators and integrins, enhancing keratinocyte motility and attachment, effects not previously associated with TNF alpha. Also unanticipated was the influence of TNF alpha upon keratinocyte cell fate by regulating cell-cycle and apoptosis-associated genes. Therefore, TNF alpha initiates not only the initiation of inflammation and responses to injury, but also the subsequent epidermal repair. The results provide new insights into the harmful and beneficial TNF alpha effects and define the mechanisms and genes that achieve these outcomes, both of which are important for TNF alpha-targeted therapies.

  8. Association of interleukin-6 and C-reactive protein genetic polymorphisms levels with venous thromboembolism

    Institute of Scientific and Technical Information of China (English)

    Ailiman Mahemuti; Kailibinuer Abudureheman; Xiaimuxikamaier Aihemaiti; HU Xue-mei; XIA Yu-ning; TANG Bao-peng; Halmurat Upur

    2012-01-01

    Background Increased levels of interleukin-6(IL-6)and C-reactive protein(CRP)have been reported in patients with venous thromboembolisms(VTE).However,prospective studies did not confirm an association between IL-6,CRP and their polymorphism with the risk of V-TE.Methods One hundred and forty patients(including 66 males and 74 females,mean age(55.55±17.11)years)and one hundred and sixty controls(including 74 males and 86 females,mean age(56.58±12.24)years)were involved.An enzyme linked immunosorbent assay(ELISA)method was used for detecting the serum levels of inflammatory factors IL-6 and CRP in both groups.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used for analyzing the distribution of polymorphisms at the-572C/G and-597G/A sites of the promoter of the IL-6 gene and at 1059G/C of the CRP gene.Results Serum levels of IL-6 and CRP were significantly higher in the VTE group than in the control group(P<0.05).The frequencies of-572C/G promoter polymorphisms CC,CG,and GG in the IL-6 gene were found to be 34%,48%,and 18%,respectively,and the derived allele frequencies for the C and G alleles were 58% and 42%.There was a significant difference in the-572C/G promoter polymorphisms between the VTE group and control group(P<0.05).For the-597G/A polymorphism,individuals all carried the GG and GA type;AA genotypes were not detected.The frequency of the GG,GC,and CC genotypes at the CRP1059G/C promoter was 87.57%,7.86% and 3.57% in VTE group,while 86.25%,10%,and 3.75% in control group,respectively.The frequency of G and C alleles at CRP 1059G/C was 91.43%and 8.57% in VTE group and 91.56% and 8.44% in the control group.The results showed that there was no statistically significant difference of 1059G/C genotype and mutation frequency of the allele between the VTE group and control group(P>0.05).Multiple Logistic regression analysis showed CC homozygotes of the IL-6-572G/C,body mass index(BMI),and CRP

  9. The adaptor protein TRAF3 inhibits interleukin-6 receptor signaling in B cells to limit plasma cell development.

    Science.gov (United States)

    Lin, Wai W; Yi, Zuoan; Stunz, Laura L; Maine, Christian J; Sherman, Linda A; Bishop, Gail A

    2015-09-01

    Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an adaptor protein that inhibits signaling by CD40 and by the receptor for B cell-activating factor (BAFF) and negatively regulates homeostatic B cell survival. Loss-of-function mutations in TRAF3 are associated with human B cell malignancies, in particular multiple myeloma. The cytokine interleukin-6 (IL-6) supports the differentiation and survival of normal and neoplastic plasma cells. We found that mice with a deficiency in TRAF3 specifically in B cells (B-Traf3(-/-) mice) had about twice as many plasma cells as did their littermate controls. TRAF3-deficient B cells had enhanced responsiveness to IL-6, and genetic loss of IL-6 in B-Traf3(-/-) mice restored their plasma cell numbers to normal. TRAF3 inhibited IL-6 receptor (IL-6R)-mediated signaling by facilitating the association of PTPN22 (a nonreceptor protein tyrosine phosphatase) with the kinase Janus-activated kinase 1 (Jak1), which in turn blocked phosphorylation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Consistent with these results, the number of plasma cells in the PTPN22-deficient mice was increased compared to that in the wild-type mice. Our findings identify TRAF3 and PTPN22 as inhibitors of IL-6R signaling in B cells and reveal a previously uncharacterized role for TRAF3 in the regulation of plasma cell differentiation.

  10. Interleukin-6 inhibition for treatment of rheumatoid arthritis: A review of tocilizumab therapy

    Directory of Open Access Journals (Sweden)

    Aarat M Patel

    2010-10-01

    Full Text Available Aarat M Patel1,2, Larry W Moreland11Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA; 2Division of Pediatric Rheumatology, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USAAbstract: The dawn of the biologic era has been an exciting period for clinical research and patient care in rheumatoid arthritis (RA. Targeted biologic therapies have changed the outcome of this disease and made remission a realistic outcome for many patients. Tocilizumab (TCZ, Actemra®, is a humanized monoclonal antibody against the interleukin 6 receptor and has been approved in many countries for the treatment of moderate to severe RA. There have been a number of important clinical trials demonstrating the efficacy of TCZ in active rheumatoid arthritis. This review summarizes the data on efficacy, patient-reported outcomes, adverse events, and safety from some of these trials. Current trends in clinical practice will be discussed. It is difficult to place TCZ and many new medications in the algorithm of treatment at present. However, the next few years will hopefully reveal their role as we better define abnormal immune processes in individuals with RA.Keywords: tocilizumab, rheumatoid arthritis, interleukin-6, biologics

  11. Prediction on the binding domain between human interleukin-6 and its receptor

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Based on the spatial conformations of human interleukin-6 (hIL-6) derived from nuclear magnetic resonance analysis and human interleukin-6 receptor (hIL-6R) modeled with homology modeling method using human growth hormone receptor as template, the interaction between hIL-6 and its receptor (hIL-6R) is studied with docking program according to the surface electrostatic potential analysis and spatial conformation complement. The stable region structure composed of hIL-6 and hIL-6R is obtained on the basis of molecular mechanism optimization and molecular dynamics simulation. The binding domain between hIL-6 and hIL-6R is predicted theoretically. Furthermore, the especial binding sites that influence the interaction between hIL-6 and hIL-6R are confirmed. The results lay a theoretical foundation for confirming the active regions of hIL-6 and designing novel antagonist with computer-guided techniques.

  12. Prediction on the binding domain between human interleukin-6 and its receptor

    Institute of Scientific and Technical Information of China (English)

    冯健男; 任蕴芳; 沈倍奋

    2000-01-01

    Based on the spatial conformations of human interleukin-6 (hlL-6) derived from nuclear magnetic resonance analysis and human interleukin-6 receptor (hlL-6R) modeled with homology modeling method using human growth hormone receptor as template, the interaction between hlL-6 and its receptor (hIL-6R) is studied with docking program according to the surface electrostatic potential analysis and spatial conformation complement. The stable region structure composed of hlL-6 and hlL-6R is obtained on the basis of molecular mechanism optimization and molecular dynamics simulation. The binding domain between hIL-6 and hIL-6R is predicted theoretically. Furthermore, the especial binding sites that influence the interaction between hlL-6 and hlL-6R are confirmed. The results lay a theoretical foundation for confirming the active regions of hlL-6 and designing novel antagonist with computer-guided techniques.

  13. Rs12976445 Polymorphism is Associated with Risk of Diabetic Nephropathy Through Modulating Expression of MicroRNA-125 and Interleukin-6R

    OpenAIRE

    Li, Cunjie; Lei, Ting

    2015-01-01

    Background Diabetic nephropathy (DN) is one of the most significant long-term complications of diabetes mellitus (DM), and it is a primary risk factor for end-stage renal disease. MicroRNAs (miRNAs) play important roles in regulating the expression of genes, including interleukin-6R (IL-6R), which has been reported to be involved in the development of DNDN. The aim of this study was to identify the dysregulation of miRNA and its target responsible for the development of DN in DM. Material/Met...

  14. Interleukin-6 in peripheral blood and inflammatory sites in Behçet's disease

    Directory of Open Access Journals (Sweden)

    K. Hamzaoui

    1992-01-01

    Full Text Available Interleukin-6, a potent pro-inflammatory cytokine, might be involved in Behçet's disease (BD pathological pathways. We investigated IL-6 levels in sera and synovial fluids collected from BD patients. The IL-6 production was also studied in vivo, by measuring its activity in culture supernatants of PBMC and alveolar macrophages, stimulated or not with LPS. The patients with BD were compared to RA patients and healthy controls. High IL-6 levels were observed in sera, synovial fluid and LPS stimulated PBMC supernatants, from active BD patients, similar to those of RA patients. Alveolar macrophages production of IL-6 was significantly elevated in two active BD patients with an interstitial pneumonia, when compared to controls. These elevated levels of IL-6 suggest its involvement in the inflammatory sites of BD, which may be related to the progression of the acute lesions, at least in the joints and in the lungs.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    LENUS (Irish Health Repository)

    O'Donovan, Aoife

    2012-02-01

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

  18. Increased production of interleukin-6 by T lymphocytes from patients with multiple myeloma.

    Science.gov (United States)

    Lapeña, P; Prieto, A; Garcia-Suarez, J; Reyes, E; San Miguel, J; Jorda, J; Alvarez-Mon, M

    1996-01-01

    Alterations in T lymphocyte functions may affect other cellular components of the immune system. Several lymphokines produced by T cells are involved in the proliferation and differentiation of human B lymphocytes. Alterations in the secretion of these molecules may be implicated in the development of B cell lymphoproliferative diseases. We have investigated the production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by T lymphocytes from 14 patients with multiple myeloma (MM) and 16 healthy controls. The phenotypical and functional characteristics of these T lymphocytes were also studied. The proliferative response to vegetal lectin phytohemagglutinin (PHA) stimulation was decreased in T lymphocytes from MM patients (p 0.05) but not by exogenous IL-6 (p lectin stimulation, the production of IL-2 by T lymphocytes from those patients was normal, while IL-6 secretion was increased.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Exercising muscle releases interleukin-6 (IL-6), but the mechanisms controlling this process are poorly understood. This study was performed to test the hypothesis that the IL-6 release differs in arm and leg muscle during whole-body exercise, owing to differences in muscle metabolism. Sixteen...... lateralis and deltoideus. During exercise, IL-6 release was similar between men and women and higher (P 12 ng min(-1) (kg lean limb mass)(-1), respectively). Blood flow (425 ± 36 and 554 ± 35 ml min(-1) (kg lean limb mass)(-1)) and fatty acid uptake (26...... ± 7 and 47 ± 7 µmol min(-1) (kg lean limb mass)(-1)) were lower, glucose uptake similar (51 ± 12 and 41 ± 8 mmol min(-1) (kg lean limb mass)(-1)) and lactate release higher (82 ± 32 and -2 ± 12 µmol min(-1) (kg lean limb mass)(-1)) in arms than legs, respectively, during exercise (P

  1. Interleukin-6 receptor expression and localization after transient global ischemia in gerbil hippocampus.

    Science.gov (United States)

    Vollenweider, Florence; Herrmann, Martina; Otten, Uwe; Nitsch, Cordula

    2003-04-24

    Ischemia results in increased interleukin-6 (IL-6) expression in the brain. To prove a connection between IL-6 upregulation and IL-6 receptor (IL-6R) expression following ischemia, we analyzed cell-type specific expression changes of IL-6R using transient global ischemia in the gerbil as a model. In sham operated animals, IL-6R mRNA and protein were mainly detected in hippocampal pyramidal cells and interneurons. After ischemia, IL-6R was expressed in neurons but there was no increase during the peak IL-6 expression. Neuronal IL-6R mRNA and protein decreased in parallel with pyramidal cell death, starting 2 days after ischemia. Double-labeling experiments revealed that in postischemic hippocampus IL-6R was not present in GFAP-reactive astrocytes but that the surviving parvalbumin containing interneurons expressed IL-6R mRNA.

  2. Interleukin-6 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Yoshiaki Furuya

    2010-01-01

    Full Text Available Interleukin-6 (IL-6 is a pleiotropic cytokine with a wide range of biologic activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Recent accumulating evidence indicates a pathologic role for IL-6 in promoting proliferation of both smooth muscle and endothelial cells in the pulmonary arterioles, resulting in development of pulmonary arterial hypertension (PAH. Here, we describe a patient with mixed connective tissue disease and severe, refractory PAH. Her functional activity and hemodynamic parameters dramatically responded to tocilizumab, a humanized monoclonal antibody to human IL-6 receptor, which was aimed at treating multicentric Castleman's disease. It appears that IL-6 blockade may hold promise as an adjunct drug in treatment of PAH in idiopathic form as well as in association with connective tissue disease.

  3. Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OHD concentrations in healthy women

    Directory of Open Access Journals (Sweden)

    Heffernan Mary E

    2008-07-01

    Full Text Available Abstract Background Circulating 25 hydroxyvitamin D (25 (OHD, an accurate measure of vitamin D status, is markedly greater in individuals with increased exposure to ultraviolet B (UVB light via sunlight or the use of artificial UV light. Aside from the known relationship between vitamin D and bone, vitamin D has also been implicated in immune function and inflammation. Furthermore, a mass of evidence is accumulating that vitamin D deficiency could lead to immune malfunction. Our overall objective was to study the relationship between vitamin D status (as determined by serum 25(OH D concentrations and inflammatory markers in healthy women. Methods This observational study included 69 healthy women, age 25–82 years. Women with high UVB exposure and women with minimal UVB exposure were specifically recruited to obtain a wide-range of serum 25(OHD concentrations. Health, sun exposure and habitual dietary intake information were obtained from all subjects. Body composition was determined by dual-energy-x-ray absorptiometry. A fasting blood sample was collected in the morning and analyzed for serum 25(OHD, parathyroid hormone (iPTH, estradiol (E2, cortisol, and inflammatory markers [tumor necrosis factor -alpha (TNF-α, interleukin-6 and -10 (IL-6, IL-10, and C-reactive protein (CRP]. Results Women with regular UVB exposure (Hi-D had serum 25(OHD concentrations that were significantly higher (p p Conclusion Serum 25(OHD status is inversely related to TNF-α concentrations in healthy women, which may in part explain this vitamin's role in the prevention and treatment of inflammatory diseases. Results gleaned from this investigation also support the need to re-examine the biological basis for determining optimal vitamin D status.

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

    KAUST Repository

    Ammirati, Enrico

    2012-08-29

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

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

    Directory of Open Access Journals (Sweden)

    Juan E. Losa García

    1999-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-01

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

  7. DIAGNOSTIC VALUE OF SIMULTANEOUS MEASUREMENT OF PROCALCITONIN, INTERLEUKIN-6 AND HS CRP IN PREDICTION OF EARLY-ONSET NEONATAL SEPSIS

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    alireza abdollahi

    2012-05-01

    Full Text Available Neonatal sepsis is a major cause of morbidities and mortalities mostly remarkable in the third world nations .We aimed to assess the value of simultaneous measurement of procalcitonin (PCT and interleukin-6 (IL-6 in association with high sensitive- C reactive protein in prediction of early neonatal sepsis. We performed a follow- up study on 95 neonates who were below 12 hours (h of age, had clinical signs of sepsis or maternal risk factors for sepsis. Neonates were assigned to 4 groups including “proven early-onset sepsis”, “clinical early-onset sepsis”, “negative infectious status”, and “uncertain infectious status”. Blood samples were obtained within the first 12 h of birth repeated between 24 hours and 36 hours of age for determination of serum levels of PCT, IL-6, high sensitivie- C Reactive Protein (hs-CRP, and white blood cell (WBC count. On admission, neonates with sepsis had a higher WBC count, IL-6, PCT, and hs-CRP levels compared with those neonates without sepsis. This remained significant even after 12-24 hours of admission. Also, patients with clinical evidences of sepsis had a higher serum level of PCT and IL-6 within 12-24 hours after admission compared to the patients with uncertain sepsis. In final The combination of IL-6, hs-CRP, and PCT seems to be predictive in diagnosis of early onset neonatal sepsis.

  8. Direct and Indirect Suppression of Interleukin-6 Gene Expression in Murine Macrophages by Nuclear Orphan Receptor REV-ERBα

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    Shogo Sato

    2014-01-01

    Full Text Available It is now evident that many nuclear hormone receptors can modulate target gene expression. REV-ERBα, one of the nuclear hormone receptors with the capacity to alter clock function, is critically involved in lipid metabolism, adipogenesis, and the inflammatory response. Recent studies suggest that REV-ERBα plays a key role in the mediation between clockwork and inflammation. The purpose of the current study was to investigate the role of REV-ERBα in the regulation of interleukin-6 (il6 gene expression in murine macrophages. REV-ERBα agonists, or overexpression of rev-erbα in the murine macrophage cell line RAW264 cells, suppressed the induction of il6 mRNA following a lipopolysaccharide (LPS endotoxin challenge. Also, rev-erbα overexpression decreased LPS-stimulated nuclear factor κB (NFκB activation in RAW264 cells. We showed that REV-ERBα represses il6 expression not only indirectly through an NFκB binding motif but also directly through a REV-ERBα binding motif in the murine il6 promoter region. Furthermore, peritoneal macrophages from mice lacking rev-erbα increased il6 mRNA expression. These data suggest that REV-ERBα regulates the inflammatory response of macrophages through the suppression of il6 expression. REV-ERBα may therefore be identified as a potent anti-inflammatory receptor and be a therapeutic target receptor of inflammatory diseases.

  9. Genetic polymorphism of interleukin-6 influences susceptibility to HBV-related hepatocellular carcinoma in a male Chinese Han population.

    Science.gov (United States)

    Tang, Shengli; Yuan, Yufeng; He, Yueming; Pan, Dingyu; Zhang, Yongxi; Liu, Yuanyuan; Liu, Quanyan; Zhang, Zhonglin; Liu, Zhisu

    2014-04-01

    As a multifunctional cytokine, interleukin-6 (IL-6) plays a key role in chronic inflammation as well as tumor growth and progression of hepatitis B virus (HBV) infection. Recent studies have implicated that single nucleotide polymorphism (SNP) -572C>G (rs1800796) located within the promoter region of IL-6 gene was associated with susceptibility to several diseases. Here, a case-control study was undertaken to investigate the association between this polymorphism and HBV-related hepatocellular carcinoma (HCC) susceptibility in a Chinese Han population. A total of 900 patients with chronic HBV infection, including 505 HBV-related HCC patients and 395 HBV infected patients without HCC were enrolled, and rs1800796 polymorphism was genotyped by the TaqMan method and DNA sequencing technology. The results indicated no significant association between rs1800796 polymorphism and the risk of HBV-related HCC in all subjects; however, a significant difference was identified in male subjects. Under the dominant model, male subjects with the G allele (CG/GG) have higher susceptibility to HBV-related HCC than those with CC genotype after adjusting confounding factors (P=0.012, odds ratio [OR] 1.68, 95% confidence interval [95% CI] 1.15-2.42). Our results suggested that rs1800796 polymorphism of IL-6 gene was associated with susceptibility to HBV-related HCC in a male Chinese Han population.

  10. p32 is Required for Appropriate Interleukin-6 Production Upon LPS Stimulation and Protects Mice from Endotoxin Shock

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    Katsuhiko Sasaki

    2017-06-01

    Full Text Available Sepsis is a major cause of morbidity and mortality in seriously ill patients and mitochondrial dysfunction is associated with poor outcomes in septic patients. Although interleukin-6 (IL-6 is a good prognostic marker for sepsis, the relationship between mitochondrial dysfunction and IL-6 remains poorly understood. We identified p32/C1QBP/HABP1 as a regulator of IL-6 production in response to lipopolysaccharide (LPS. LPS induced IL-6 overproduction in p32 deficient mouse embryonic fibroblasts (MEFs through NF-κB independent but activating transcription factor (ATF 4 dependent pathways. Short hairpin RNA-based knockdown of ATF4 in p32 deficient MEFs markedly inhibited LPS-induced IL-6 production. Furthermore, MEFs treated with chloramphenicol, an inhibitor of mitochondrial translation, produced excessive IL-6 via ATF4 pathways. Using a LPS-induced endotoxin shock model, mice with p32 ablation in myeloid cells showed increased lethality and overproduction of IL-6. Thus, this study provides a molecular link how mitochondrial dysfunction leads to IL-6 overproduction and poor prognosis of sepsis.

  11. Association of interleukin-6 and interleukin-8 with poor prognosis in elderly patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Yoon, Ju-Yoon; Lafarge, Sandrine; Dawe, Dave; Lakhi, Sunjay; Kumar, Rajat; Morales, Carmen; Marshall, Aaron; Gibson, Spencer B; Johnston, James B

    2012-09-01

    In population studies, the relative survival in chronic lymphocytic leukemia (CLL) decreases with age. In this study, we demonstrated in a cohort of 189 patients from a CLL clinic that overall survival was lower in the sub-cohort of patients aged ≥ 70 years, but causes of death were similar for all age groups, being progressive CLL, secondary malignancies and infections. As normal individuals age, the plasma levels of inflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, can increase. In our patients with CLL, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) levels increased with age to a greater degree than in normal individuals, and the levels correlated closely with plasma β(2)-microglobulin and with one another. In addition, in patients ≥ 70 years, IL-6 was found to be a better prognostic marker than immunoglobulin variable heavy chain gene (IgV(H)) status. In vitro studies demonstrated that IL-6 and IL-8 could enhance the binding of CLL cells to stromal cells, suggesting that their clinical activity may be mediated through their effects on the microenvironment. Thus, plasma IL-6 is an important prognostic marker for the elderly with CLL, and this study highlights that the utility of prognostic markers may depend on patient age.

  12. Interleukin-6 Gene Promoter-572 C Allele May Play a Role in Rate of Disease Progression in Multiple Sclerosis

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    Judith M. Greer

    2012-10-01

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. One important mediator of immune responses and inflammation is interleukin-6 (IL-6. Previously, elevated levels of IL-6 in mononuclear cells in blood and in brain tissue from MS patients have been reported. Various polymorphisms in the promoter region of the IL6 gene have also been linked with IL-6 protein levels. In MS, several small studies have investigated whether two IL6 promoter polymorphisms (−597 G>A and −174 G>C correlate with MS susceptibility, but with varying results. In the present study, we analyzed these polymorphisms, together with an additional polymorphism (−572 G>C in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different −597 or −174 IL6 promoter alleles or genotypes. There was a slight reduction in the percentage of individuals with MS who carried a C allele at position −572, although this was not significant after correction for multiple comparisons. Interestingly, however, the −572 C allele showed a significant correlation with the MS severity score, suggesting a possible role in disease progression.

  13. Moderate Hypoxia Down-Regulates Interleukin-6 Secretion and TLR4 Expression in Human Sw.71 Placental Cells

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    Koumei Shirasuna

    2015-07-01

    Full Text Available Background/Aims: The placenta is a vital organ for pregnancy. Many in vitro placental experiments are conducted under 21% O2; however, O2 tension could influence cellular functions, including cytokine secretion. We investigated the effects of oxygen tension between moderate hypoxia (5% O2 and normoxia (21% O2 by testing the hypothesis that moderate hypoxia regulates cellular phenotypes differently from normoxia in human trophoblast cells. Methods and Results: Sw.71 trophoblast cells were incubated under normoxic or moderately hypoxic conditions. Cells were also treated with lipopolysaccharide (LPS as a Toll-like receptor 4 (TLR4 ligand inducing inflammation. Interleukin-6 (IL-6 as an inflammatory cytokine was determined, and TLR4, hypoxia-induced factor-1α (HIF1α, and reactive oxygen species (ROS production were detected. Moderate hypoxia increased HIF1α expression and cell proliferation and acted by two different mechanisms to decrease IL-6 secretion compared with normoxia: it limits the TLR4 expression and ROS production. Treatment with cobalt chloride as an HIF1 activator inhibited IL-6 secretion and TLR4 expression; this effect was reversed on treatment with PX-12 as an HIF1 suppressor. Conclusion: IL-6 secretion, TLR4 expression, and ROS production, classical markers of inflammation, are down-regulated by moderate hypoxia, and HIF1α and ROS have a potential to regulate these responses in human trophoblast cells.

  14. Identification of the interleukin-6/oncostatin M response element in the rat tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter.

    Science.gov (United States)

    Bugno, M; Graeve, L; Gatsios, P; Koj, A; Heinrich, P C; Travis, J; Kordula, T

    1995-01-01

    The rat tissue inhibitor of metalloproteinase 1 (TIMP-1) gene is expressed in rat hepatocytes, and this expression is up-regulated by interleukin 6 (IL-6). We report here the cloning of the 5' flanking region of the rat TIMP-1 gene and identification of an IL-6/oncostatin M (OSM) response element at -64 to -36 which functions in hepatic cells. Within this element we have identified two functional binding sites for transcription factors AP-1 (activatory protein-1) and STAT (signal transducer and activator of transcription). IL-6/OSM stimulation induces binding of a protein, identified as STAT3, to the IL-6/OSM response element, while binding of the AP-1 protein was constitutive. Binding sites for both AP-1 and STAT3 are necessary for full responsiveness of the TIMP-1 promoter to IL-6/OSM, as shown by deletion and mutation analysis. Furthermore, the entire IL-6/OSM response element conferred responsiveness onto a heterologous promoter, whereas this has not been observed when AP-1 and STAT elements were separately tested. Images PMID:8559663

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

    Science.gov (United States)

    Smidowicz, Angelika; Regula, Julita

    2015-11-01

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

  16. Effect of Nutritional Status and Dietary Patterns on Human Serum C-Reactive Protein and Interleukin-6 Concentrations12

    Science.gov (United States)

    Smidowicz, Angelika; Regula, Julita

    2015-01-01

    The inflammatory process plays an important role in the pathogenesis of many chronic diseases, such as cardiovascular diseases, diabetes mellitus type 2, and metabolic syndrome. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) are widely tested inflammatory markers involved in the development of these diseases. Several studies indicate a relation between nutritional status and the concentrations of human high-sensitivity CRP and IL-6. Similarly, the role of diet in reducing inflammation and thereby modulating the risk of non-communicable diseases is supported by numerous studies. This review focuses on the effects of the selected nutrition models in humans on the concentrations of CRP and IL-6. It seems that the Mediterranean diet model is most effective in inhibiting inflammation. The Dietary Approaches to Stop Hypertension model and the plant nutrition model also have proven to be beneficial. The data on low-fat and low-carbohydrate diets are inconclusive. Comprehensive studies are necessary, taking into account the cumulative effect of dietary and other factors on the inflammatory process. PMID:26567198

  17. Essential oil of Myrtus communis inhibits inflammation in rats by reducing serum IL-6 and TNF-alpha.

    Science.gov (United States)

    Maxia, Andrea; Frau, Maria Assunta; Falconieri, Danilo; Karchuli, Manvendra Singh; Kasture, Sanjay

    2011-10-01

    The topical antiinflammatory activity of the essential oil of Myrtus communis L. was studied using croton oil induced ear edema and myeloperoxidase (MPO) activity in mice, and cotton pellet induced granuloma, and serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rats. On topical application, the oil exhibited a significant decrease in the ear edema as well as MPO activity. The oil also inhibited cotton pellet-induced granuloma and serum TNF-alpha and IL-6. It can be concluded that the essential oil of Myrtus communis reduces leukocyte migration to the damaged tissue and exhibits antiinflammatory activity.

  18. Anti-inflammatory activity of Pistacia lentiscus essential oil: involvement of IL-6 and TNF-alpha.

    Science.gov (United States)

    Maxia, Andrea; Sanna, Cinzia; Frau, Maria Assunta; Piras, Alessandra; Karchuli, Manvendra Singh; Kasture, Veena

    2011-10-01

    The topical anti-inflammatory activity of essential oil of Pistacia lentiscus L. was studied using carrageenan induced rat paw edema and cotton pellet induced granuloma. The effect on serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in rats inserted with cotton pellet was also investigated. On topical application, the oil exhibited a significant decrease in paw edema. The oil also inhibited cotton pellet-induced granuloma, and reduced serum TNF-alpha and IL-6. It can be concluded that the essential oil of Pistacia lentiscus reduces leukocyte migration to the damaged tissue and exhibits anti-inflammatory activity.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  1. Brain immune interactions and air pollution: Macrophage inhibitory factor (MIF, Prion cellular protein (PrPC, Interleukin-6 (IL-6, Interleukin 1 receptor antagonist (IL-1Ra, and Interleukin-2 (IL-2 in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe versus low air pollution.

    Directory of Open Access Journals (Sweden)

    Lilian eCalderon-Garciduenas

    2013-10-01

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

  2. 重性抑郁障碍患者与肿瘤坏死因子ɑ基因启动子区多态性的相关性研究%Association of the Polymorphisms in the Promoter Region of Tumor Necrosis Factor and Interleukin 6 Gene with Major Depressive Disorder

    Institute of Scientific and Technical Information of China (English)

    马心慧; 付瑜; 曹淑杰; 王双力; 武伟晶; 王军利; 王芳

    2016-01-01

    Objective To study the relationship between the -857C/T and-308G/A of tumor necrosis factor αgene ( TNF-α) polymorphisms and major depressive disorder .Methods Genomic DNA was gotten from the venous blood leukocytes from 393 patients with major depressive disorder and 393 healthy individuals.Genotype all of the polymor-phisms by means of PCR -restriction fragment length poly -morphisms ( PCR-RFLP).Allele and genotype frequencies were researched by SPSS13.0 software.Results There were obvious differences in both genotype and allele frequencies of -857 C/T of TNF-αgene between the major depressive disorder and control groups ( P<0.05 ) .The allele T of -857C/T in male major depressive disorder group was obviously higher than that in contol group ( OR=0.31,95% CI:0.22-0.44 , P<0.01 ).The allele A of -308 G/A in female major depressive disorder group was obviously higher than that in contol group ( OR=0.34 ,95% CI:0.25-0.65 , P<0.01 ).Conclusions There is a correlation between -857C/T of TNF-αgene and major depressive disorder ,individuals with T allele of -857C/T are susceptible to major depressive disorder,and there is a relationship between -857C/T and negative symptom score.%目的:探讨肿瘤坏死因子α(tumor necrosis factor,TNF-α)基因启动子区-308G/A、-857C/T位点多态性与重性抑郁障碍症发生的相关性。方法采用聚合酶链限制性片段长度多态性( PCR-RFLP)分析方法检测393例重性抑郁障碍症患者和393名健康对照各个多态性位点的基因型,采用SPSS 13.0进行统计学分析。结果 TNF-α基因启动子-857 C/T位点的等位基因和基因型频率分布在正常对照组与重性抑郁障碍症组间存在统计学意义( P<0.05)。其中,男性重性抑郁障碍症组与对照组在-857 T的等位基因频率上存在显著差异( OR=0.31,95%CI:0.22-0.44,P<0.01),而女性病例组与对照组在-308 A位点的等位基因

  3. Effects of dexmedetomidine on plasma concentrations of tumor necrosis factor-α and interleukin-6 in patients undergoing radical esophagectomy with one-lung ventilation%右美托咪定对食管癌根治术单肺通气患者肿瘤坏死因子-α和白细胞介素-6的影响

    Institute of Scientific and Technical Information of China (English)

    付琦; 庞志路; 韩雪萍

    2012-01-01

    目的 观察右美托咪定对食管癌根治术单肺通气患者血浆肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6水平的影响.方法 60例拟行食管癌根治术的患者,随机分为D1组、D2组和C组,每组20例.D1组麻醉诱导前0.6μg/kg静脉泵注右美托咪定;D2组麻醉诱导后以0.3μg/(kg·h)静脉泵注右美托咪定;C组为对照组.分别测定麻醉诱导前20 min(T0),气管插管后10 min(T1),单肺通气30 min(T2),单肺通气90 min(T3)及再次双肺通气后10 min(T4)5个时间点血浆中TNF-α和IL-6浓度.结果 3组患者血浆TNF-α水平在T3、T4时点较T0高(P <0.05);D1组和D2组在T3(10.5±2.5,11.1 ±2.6)、T4(11.2±2.4,11.8±2.7)时点较C组增高(P<0.05).3组患者血浆IL-6水平在T4时点较T0高(P <0.05);D1组和D2组在T4时点(23.2±3.3,23.9±3.2)较C组增高(P<0.05).结论 术前静脉泵注0.6 μg/kg及术中持续以0.3μg,/(kg·h)静脉泵注右美托咪定均能抑制食管癌根治术单肺通气患者血浆中TNF-α和IL-6水平升高.%Objective To observe the changes in plasma concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in patients undergoing radical esophagectomy during one-lung ventilation.Methods Sixty patients undergoing open radical esophagectomy were randomly divided into three groups:group D1 was given dexmedetomidine intravenously at 0.6 μg/kg 20 min before induction of anesthesia; group D2 was given dexmedetomidine intravenously at 0.3 μg/(kg· h) after induction of anesthesia; group C served as control group.The plasma concentrations of TNF-α and IL-6 were measured by using enzyme linked immunosorbent assay (ELISA) at 20 min betore anesthesia induction (T0),10 min after tracheal intubation (T1),30 min after one-lung ventilation (T2),90 min after one-lung ventilation (T3) and 10 min after resuming two-lung ventilation (T4).Results As compared with T0,plasma TNF-α concentration was increased critically at T3 and T4 in three groups.Plasma TNF

  4. Non-linear antigenic regions in epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) studied by EGF-TGF alpha chimaeras.

    Science.gov (United States)

    van de Poll, M L; van Rotterdam, W; Gadellaa, M M; Stortelers, C; van Vugt, M J; van Zoelen, E J

    2000-07-01

    With the help of 16 chimaeras between human epidermal growth factor (hEGF) and human transforming growth factor alpha (hTGF alpha), a detailed analysis was performed on the epitope recognized by two polyclonal antibodies raised against hEGF, and one polyclonal antibody raised against hTGF alpha. All three antibodies recognized essentially the same antigenic site, a non-linear and conformation-dependent sequence that is located near the second and fourth disulphide-bonded cysteines and that includes the start of the B-loop beta-sheet. The epitope recognized by the anti-hEGF antibodies was further characterized using 8 chimaeras between hEGF and an EGF-repeat from Drosophila Notch and was found to include Met(21), Ala(30) and Asn(32). All three polyclonal antibodies were able to neutralize the biological activity of the respective growth factor when tested on 32D murine haematopoietic progenitor cells transfected with ErbB-1, indicating that the receptor binding domain is shielded upon binding of the antibody.

  5. The level changes of brain-derived neurotrophic factors, interleukin-2 and interleukin-6 in serum of patients with depression and obsessive-compulsive disorder before and after treatment and their clinical significance%抑郁症与强迫症患者治疗前后血清脑源性神经营养因子、白介素-2及白介素-6水平变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    江鸿波; 李莉欣

    2013-01-01

    Objective To explore the level changes of brain-derived neurotrophic factors (BDNF), interleukin-2 (IL-2) and interleukin-6 (IL-6) in serum of patients with depression and obsessive-compulsive disorder before and after treatment and the influential factors. Methods There were 30 cases in depression group (depression patients), 30 cases in obsessive-compulsive disorder group (patients with obsessive-compulsive disorder) and 30 cases in control group. On the basis of paroxetine therapy, the psychological therapy was administered in the depression group and the obsessive-compulsive disorder group. The levels of BDNF, IL-2 and IL-6 in serum of the three groups were detected by enzyme-linked immunosorbent assay (ELISA). Before and after treatment, the scale assessment was conducted. Hamilton depression rating scale (HAMD) was applied to assess the symptoms of depression while yale-brown obsessive compulsive scale (Y-BOCS) to evaluate obsessive compulsive symptoms. The relative analysis was conducted between the levels of BDNF, IL-2 and IL-6 in serum of patients with depression and obsessive - compulsive disorder and HAMD total score, Y-BOCS total score, disease duration, age and gender. Results After treatment, serum BDNF level in the depression group significantly increased, while the levels of IL-2 and IL-6 obviously decreased, but BDNF level was still lower than that in the control group. Serum BDNF level in obsessive-compulsive disorder group conspicuously elevated, whereas IL-2 level markedly reduced, but BDNF level was still lower than that in the control group. In the depression group, serum BDNF level was associated with HAMD score negatively, while the levels of IL-2 and IL-6 in serum were related to HAMD score positively. In the obsessive-compulsive disorder group, serum BDNF level is associated with Y-BOCS score negatively, while serum IL-6 was related to Y -BOCS score positively. Conclusion BDNF, IL-2 and IL-6 can provide possible evidences for the i

  6. 乌司他丁联合阿拓莫兰治疗感染性休克患者血清白细胞介素6、肿瘤坏死因子α及降钙素原水平的变化及预后观察%Changes levels of serum interleukin 6, tumor necrosis factor αand procalcitonin and prognosis of pa-tients with septic shock with the treatment of combination of ulinastatin and Atomolan

    Institute of Scientific and Technical Information of China (English)

    方向明; 潘嘉宇; 易高

    2016-01-01

    Objective To investigate the changes levels of serum interleukin 6(IL⁃6),tumor necrosis factor α( TNF⁃α) and procalcitonin( PCT) and prognosis of patients with septic shock with the treatmentof uli⁃nastatin and Atomolan. Methods Sixty cases patients with septic shock in Fifth Hospital Affiliated to Guang⁃zhou Medical University from May 2015 to April 2016 were selected,and divided into ulinastatin group,Atomolan group and combined group according to the table of random numbers,each group with 20 cases. Hospital stay in ICU,mechanical ventilation time,APACHEⅡ score after treatment,the level of IL⁃6,TNF⁃α,PCT,malondialde⁃hyde(MDA),superoxide dismutase(SOD) before and after treatment,and prognosis of patients of three groups were compared. Results Hospital stay in ICU,mechanical ventilation time,APACHEⅡ score after treatment of combined group were significantly lower than ulinastatin group and Atomolan group,the differences were statisti⁃cally significant( P0. 05). After treatment,the level of IL⁃6, TNF⁃α,PCT and MDA of the combined group were significantly lower than that of ulinastatin group and Atomo⁃lan group,while SOD was significantly higher than the other two groups,the differences were statistically signifi⁃ cant( P<0. 05 ) . The MODS incidence, mortality rates of ulinastatin group were 30. 00%( 6/20 ) , 20. 00%(4/20),of Atomolan group were 35. 00%(7/20),15. 00%(3/20),of combined group were 5. 00%(1/20), 5. 00%( 1/20) . The MODS incidence,mortality rates of combined group were lower than the other two groups( P<0. 05).Conclusion Ulinastatin combined with Atomolan in treatment of septic shock with remarkable results, can significantly improve the serum IL⁃6,TNF⁃α,PCT and other important factors,optimize the prognosis,it is worthy of promotion.%目的:探讨乌司他丁联合阿拓莫兰治疗感染性休克患者血清IL⁃6、肿瘤坏死因子α( TNF⁃α)及降钙素原( PCT)水平的

  7. Synergism between human tumor necrosis factor and human interferon-alpha: effects on cells in culture.

    Science.gov (United States)

    Orita, K; Ando, S; Kurimoto, M

    1987-08-01

    The cytostatic and cytotoxic effects of highly purified natural human tumor necrosis factor (HuTNF-alpha) and natural human interferon-alpha (HuIFN-alpha) on 23 cell lines were studied in vitro. Natural HuTNF-alpha showed cytostatic and cytotoxic effects on PC-9, KHG-2, HT-1197, KG-1 and L-929 cells, and HuIFN-alpha showed both effects on KHG-2 and Daudi cells. A mixture of HuTNF-alpha and HuIFN-alpha (1:1, by unit) showed cytostatic and cytotoxic effects on HuTNF-alpha- or HuIFN-alpha-resistant cell lines such as KB, KATO-III, HEp-2, P-4788, as well as on HuTNF-alpha- or HuIFN-alpha-susceptible cells. Thus, the combined preparation of HuTNF-alpha and HuIFN-alpha expanded the spectrum of sensitive cells. The dosage of the mixed preparation required to produce 50% inhibition of cell growth was less than 20% of that of HuTNF-alpha or HuIFN-alpha alone. These results indicate that the cytostatic and cytotoxic effects of HuTNF-alpha and HuIFN-alpha are synergistically enhanced when they are administered together.

  8. Synergism between human tumor necrosis factor and human interferon-alpha: effects on cells in culture.

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    Orita,Kunzo

    1987-08-01

    Full Text Available The cytostatic and cytotoxic effects of highly purified natural human tumor necrosis factor (HuTNF-alpha and natural human interferon-alpha (HuIFN-alpha on 23 cell lines were studied in vitro. Natural HuTNF-alpha showed cytostatic and cytotoxic effects on PC-9, KHG-2, HT-1197, KG-1 and L-929 cells, and HuIFN-alpha showed both effects on KHG-2 and Daudi cells. A mixture of HuTNF-alpha and HuIFN-alpha (1:1, by unit showed cytostatic and cytotoxic effects on HuTNF-alpha- or HuIFN-alpha-resistant cell lines such as KB, KATO-III, HEp-2, P-4788, as well as on HuTNF-alpha- or HuIFN-alpha-susceptible cells. Thus, the combined preparation of HuTNF-alpha and HuIFN-alpha expanded the spectrum of sensitive cells. The dosage of the mixed preparation required to produce 50% inhibition of cell growth was less than 20% of that of HuTNF-alpha or HuIFN-alpha alone. These results indicate that the cytostatic and cytotoxic effects of HuTNF-alpha and HuIFN-alpha are synergistically enhanced when they are administered together.

  9. The role of tumour necrosis factor alpha and soluble tumour necrosis factor alpha receptors in the symptomatology of schizophrenia.

    Science.gov (United States)

    Turhan, Levent; Batmaz, Sedat; Kocbiyik, Sibel; Soygur, Arif Haldun

    2016-07-01

    Background Immunological mechanisms may be responsible for the development and maintenance of schizophrenia symptoms. Aim The aim of this study is to measure tumour necrosis factor-alpha (TNF-α), soluble tumour necrosis factor-alpha receptor I (sTNF-αRI), and soluble tumour necrosis factor-alpha receptor II (sTNF-αRII) levels in patients with schizophrenia and healthy individuals, and to determine their relationship with the symptoms of schizophrenia. Methods Serum TNF-α, sTNF-αRI and sTNF-αRII levels were measured. The Positive and Negative Syndrome Scale (PANSS) was administered for patients with schizophrenia (n = 35), and the results were compared with healthy controls (n = 30). Hierarchical regression analyses were undertaken to predict the levels of TNF-α, sTNF-αRI and sTNF-αRII. Results No significant difference was observed in TNF-α levels, but sTNF-αRI and sTNF-αRII levels were lower in patients with schizophrenia. Serum sTNF-αRI and sTNF-αRII levels were found to be negatively correlated with the negative subscale score of the PANSS, and sTNF-αRI levels were also negatively correlated with the total score of the PANSS. Smoking, gender, body mass index were not correlated with TNF-α and sTNF-α receptor levels. Conclusions These results suggest that there may be a change in anti-inflammatory response in patients with schizophrenia due to sTNF-αRI and sTNF-αRII levels. The study also supports low levels of TNF activity in schizophrenia patients with negative symptoms.

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

    DEFF Research Database (Denmark)

    Penkowa, Milena; Camats, Jordi; Hadberg, Hanne

    2003-01-01

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

  11. Breviscapine reduces neuronal injury caused by traumatic brain injury insult: partly associated with suppression of interleukin-6 expression

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    Ling Jiang

    2017-01-01

    Full Text Available Breviscapine, extracted from the herb Erigeron breviscapus, is widely used for the treatment of cardiovascular diseases, cerebral infarct, and stroke, but its mechanism of action remains unclear. This study established a rat model of traumatic brain injury induced by controlled cortical impact, and injected 75 μg breviscapine via the right lateral ventricle. We found that breviscapine significantly improved neurobehavioral dysfunction at 6 and 9 days after injection. Meanwhile, interleukin-6 expression was markedly down-regulated following breviscapine treatment. Our results suggest that breviscapine is effective in promoting neurological behavior after traumatic brain injury and the underlying molecular mechanism may be associated with the suppression of interleukin-6.

  12. Racial differences in tumor necrosis factor-α-induced endothelial microparticles and interleukin-6 production

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    Brown M

    2011-08-01

    Full Text Available Michael D Brown1,3, Deborah L Feairheller1, Sunny Thakkar1, Praveen Veerabhadrappa1, Joon-Young Park21Hypertension, Molecular and Applied Physiology Laboratory, 2Cardiovascular Genomics Laboratory, Department of Kinesiology, 3Cardiovascular Research Center, School of Medicine, Temple University, Philadelphia, PA, USAAbstract: African Americans (AA tend to have heightened systemic inflammation and endothelial dysfunction. Endothelial microparticles (EMP are released from activated/apoptotic endothelial cells (EC when stimulated by inflammation. The purpose of our study was to assess EMP responses to inflammatory cytokine (TNF-α and antioxidant (superoxide dismutase, SOD conditions in human umbilical vein ECs (HUVECs obtained from AA and Caucasians. EMPs were measured under four conditions: control (basal, TNF-α, SOD, and TNF-α + SOD. Culture supernatant was collected for EMP analysis by flow cytometry and IL-6 assay by ELISA. IL-6 protein expression was assessed by Western blot. AA HUVECs had greater EMP levels under the TNF- α condition compared to the Caucasian HUVECs (6.8 ± 1.1 vs 4.7% ± 0.4%, P = 0.04. The EMP level increased by 89% from basal levels in the AA HUVECs under the TNF-α condition (P = 0.01 compared to an 8% increase in the Caucasian HUVECs (P = 0.70. Compared to the EMP level under the TNF-α condition, the EMP level in the AA HUVECs was lower under the SOD only condition (2.9% ± 0.3%, P = 0.005 and under the TNF-α + SOD condition (2.1% ± 0.4%, P = 0.001. Basal IL-6 concentrations were 56.1 ± 8.8 pg/mL/µg in the AA and 30.9 ± 14.9 pg/mL/µg in the Caucasian HUVECs (P = 0.17, while basal IL-6 protein expression was significantly greater (P < 0.05 in the AA HUVECs. These preliminary observational results suggest that AA HUVECs may be more susceptible to the injurious effects of the proinflammatory cytokine, TNF-α.Keywords: endothelium, inflammation, endothelial microparticles, African Americans

  13. Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation

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    Gerhard Hamilton

    1993-01-01

    Full Text Available In human orthotopic liver transplantation (LTX intraoperative elevations of TNF-α (> 100 pg/ml and IL-6 (>800 pg/ml have been found to correlate with early post-operative rejections and infections respectively. In this study the possible mechanism responsible for the induction of these cytokines has been investigated during liver allografting in 38 recipients. Intraoperative elevations of TNF-α (> 100 pg/ml were detected in the majority of pre-transplant endotoxin positive recipients (8/12, > 10 endotoxin units/ml, the patients turning endotoxin positive until the end of grafting (3/5, and in a subgroup (6/21 patients, apparently endotoxin negative for the whole operation. Therefore endotoxin (ET seems to stimulate release of TNF-α in approximately 50% of the patients, whereas sensitized Kupffer graft cells or immediate allograft reactivity of the host are likely to account for the remaining TNF-α positive cases. Elevations of IL-6 > 800 pg/ml were found in approximately 50% of the TNF-α positive cases, indicating partially independent regulatory pathways for IL-6 induction in the TNF-α negative patients. In agreement with a previous study, 11/13 (85% of the intraoperative TNF-α positive recipients rejected their grafts within the first 10 days post-operatively. These data demonstrate that ET/infection associated as well as ET independent/reperfusion associated intraoperative TNF-α elevations, promote the initiation of allograft rejection in human liver transplantation. The transient and low endotoxaemia caused by the liver grafting procedure performed without veno-venous bypass seems to be of minor importance in the intraoperative induction of TNF-α.

  14. Hepatocyte Growth Factor and Interleukin-6 in Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2006-06-01

    herbal compound PC-SPES: identification of activity pathways in prostate carcinoma. Cancer Res 62, 3920-4. (2002). 10. Rutter, M.M. et al...anti-IGFBP5 were used as a negative control. 40 µg total protein or immunoprecipitated proteins were analyzed on 12% NuPAGE or 4-12% Bis-Tris Gels ...right panel) in HS27a grown in 10% FCS. A 292 base fragment with in the AR mRNA (panel A) is amplified by PCR and detected by agarose gel

  15. Interleukin-6 G-174C gene polymorphism and serum resistin levels in North Indian women: potential risk of metabolic syndrome.

    Science.gov (United States)

    Gupta, A; Gupta, V; Singh, A K; Tiwari, S; Agrawal, S; Natu, S M; Agrawal, C G; Negi, M P S; Pant, A B

    2011-10-01

    The present investigations were aimed to identify the possible association between genetic polymorphism in interleukin-6 (IL-6) G-174C gene, which confers susceptibility to metabolic syndrome, and serum level of resistin in North Indian women. The study population comprised 370 unrelated Indian women (192 having abdominal obesity and 178 controls). Polymorphism in genotype (CC+GC) of IL-6 G-174C gene was determined using a combination of polymerase chain reaction (PCR) and sequence-specific primer with restriction fragment length polymorphism (RFLP) technology. Insulin resistance (IR) and serum resistin level were also analyzed along with metabolic risk factors. Of 192 abdominal obese women, 147 (76.56%) were found to have mutant CC+GC (p = 0.001) genotype and allele frequency (p = 0.001), which was significantly higher 45 (23.44%) than non-obese and their respective wild type. The mutant genotype (CC+GC) of IL-6 gene was found to be associated significantly with high triglyceride (p = 0.025) and resistin level (p obese women. Non-obese women with no signs of metabolic risk factors were found to have significantly low level of serum resistin and IR in comparison to obese women having genetic polymorphism for IL-6 G-174C gene. Study suggests that IL-6 G-174C gene is one among the susceptibility loci for metabolic syndrome in North Indian women. Genotype for this polymorphism may prove informative for prediction of genetic risk for metabolic syndrome. Further, high level of serum resistin molecules may be targeted to correlate with metabolic syndrome risk factors and could be used as early prediction marker.

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

    Science.gov (United States)

    Huang, Li-Wen; Hsieh, Bau-Shan; Cheng, Hsiao-Ling; Hu, Yu-Chen; Chang, Wen-Tsan; Chang, Kee-Lung

    2012-01-15

    Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  17. Nuclear STAT3 translocation in guinea pig and rat brain endothelium during systemic challenge with lipopolysaccharide and interleukin-6.

    Science.gov (United States)

    Rummel, Christoph; Voss, Thilo; Matsumura, Kiyoshi; Korte, Stefan; Gerstberger, Rüdiger; Roth, Joachim; Hübschle, Thomas

    2005-10-10

    During systemic inflammation, cytokines are released by immune-competent cells into the circulation, which in turn signal the brain to mediate brain-controlled signs of illness. Cytokine-responsive brain cells can be mapped by histological analysis of cytokine-induced transcription factors or transcription factor-associated molecules revealing different cell phenotypes that respond to activation of the immune system. Critical sites mediating cytokine-dependent immuneffector functions can be divided into two groups, one group of responding cells situated along a tight blood-brain barrier (BBB), and a second cell group in structures with an open BBB, e.g., the sensory circumventricular organs (CVOs). Previous reports from our group suggest that activation of the signal transducer and activator of transcription factor 3 (STAT3) during lipopolysaccharide (LPS)-induced systemic inflammation is mediated by interleukin-6 (IL-6) and occurs in astrocytes of the rat CVOs. Here we show in the guinea pig a time-dependent marked LPS-induced STAT3 activation within astrocytes and endothelial cells of the CVOs, within astrocytes located in brain structures with a functional BBB and within the brain endothelium of the entire brain. In addition, systemic treatment of rats with either rat recombinant IL-6 or LPS induced STAT3 activation in brain endothelial cells in a similar way as observed in the guinea pig brain, stressing the involvement of IL-6 in this phenomenon in a more generalized way. The STAT3-activated brain cells are located in critical target structures mediating cytokine action during LPS-induced inflammation. STAT3-controlled transcriptional activation with yet unknown cell-specific functional consequences seems to be involved in this process. (c) 2005 Wiley-Liss, Inc.

  18. Neuropeptide Y,Brain-derived neurotrophic factor,Interleukin-6 in plasma and cerebrospinal fluid of children with convulsive diseases%惊厥性疾病患儿血浆和脑脊液中神经肽Y、脑源性神经营养因子、白介素-6的水平变化及相关性研究

    Institute of Scientific and Technical Information of China (English)

    郭向阳; 焦富勇; 王侠; 高颖

    2013-01-01

    Objective:In order to study the levels and relationship of neuropeptide Y(NPY) , brain-derived neuro-trophic factor(BDNF) , interleukin-6 (IL-6) in plasma and cerebrospinal fluid(CSF) in children convulsion. Methods: 74 children with convulsive diseases were studied as following: obtaining the samples of plasma in the first day and the seventh day after being in hospital, and the samples of CSF in the lst after being in hospital. We investigated the changes of NPY, BDNF, IL-6 in plasma and CSF with radioimmunoassay(RIA). Results: In children with convulsive diseases ( febrile sei zure, epilepsy ) NPY, IL-6 in plasma and CSF were increased, but BDNF decreased. NPY, IL-6 and BDNF were higher in the seventh day than those in the first day in plasma and CSF. NPY and BDNF in different types of febrile seizures and epi leptic seizures were no difference, but IL-6 had differences. The levels of NPY, IL-6 in plasma and CSF correlated with the times of convulsion,but BDNF had no correlation to the times of convulsion. NPY, BDNF and IL-6 in plasma positively correlated with those in CSF respectively; In plasma and CSF NPY had significantly positive correlation to IL-6, and nega tive correlation to BDNF; BDNF was negatively correlation to IL-6. Conclusion: NPY, IL-6 in plasma and CSF are elevated in children with convulsive diseases and have correlation to the times of convulsion, changing in the different course of con vulsion. There are positive correlation in NPY, BDNF, IL-6 between plasma and CSF. The levels of those in plasma could indirectly reflect the levels of those in CSF. In plasma and CSF NPY have significantly positive correlation to IL-6 and nega tive correlation to BDNF; BDNF is negatively correlation to IL-6.%目的:探讨惊厥性疾病患儿血浆和脑脊液中神经肽Y(NPY)、脑源性神经营养因子(BDNF)、白介素-6(IL-6)的水平变化及相互关系.方法:选取惊厥性疾病患儿74例,分别在入院第1天、第7天采取静脉血,第7天

  19. Interleukin-6: A Sensitive Parameter for the Early Detection of Neonatal Sepsis

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    M Khaled Noor

    2009-11-01

    Full Text Available Background: Neonatal sepsis is a major cause of neonatal mortality and morbidity throughout the world. Though blood culture is the gold standard and has higher sensitivity and specificity over the hematological value and cytokine, it is not available in our community health situation and also in most of health care facilities. It is also time consuming. Therefore hematological value and interleukin-6 can be evaluated for the early diagnosis of neonatal bacterial infection. Objective: This study was conducted to see the usefulness of IL-6 as an early marker of neonatal sepsis and also to compare the sensitivity in comparison with CRP, hematological value and blood culture. Study Design: It was a quasy experimental study. Setting: This study was carried out in the neonatal unit of pediatric department, BSMMU during the period of September, 2005 to February, 2006. Method: Forty five suspected septic cases were enrolled in the study and thirty healthy newborn were taken for comparison. Venous blood sample from peripheral vein was collected on the 1st day of symptoms and/or 1st day of admission and was sent for IL-6 estimation within half an hour and estimation of IL-6 was done by using immunolyte DPC USA which employed automated chemiluminescent immunoassays. Results: Out of forty five cases of suspected-neonatal sepsis, IL-6 were positive in twenty five cases. In culture proven sepsis 100% cases had raised IL-6. In control group only five babies had raised IL-6. Three cases were culture positive, of which all were also positive for IL-6 (100%. Among the cases twenty six were CRP positive, of which twenty were also positive for IL-6 (76.92%. Conclusion: In the present study IL-6 was found to be an early marker of neonatal infection. Sensitivity was more than CRP and other hematological parameter in the first twenty four hours. Key words: Interleukin-6, Neonatal Sepsis.DOI: 10.3329/bsmmuj.v1i1.3687 BSMMU J 2008; 1(1: 1-5

  20. Family-based association study of interleukin 6 (IL6) and its receptor (IL6R) functional polymorphisms in schizophrenia in the Polish population.

    Science.gov (United States)

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Pawlak, Joanna; Permoda-Osip, Agnieszka; Twarowska-Hauser, Joanna

    2015-08-15

    Schizophrenia is a heterogeneous disorder and its etiology remains incompletely elucidated. Among possible causes, immunological factors have been implicated in its pathogenesis and course. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. Recent studies indicate a role of excessive interleukin-6 (IL6) signaling in the pathogenesis of schizophrenia. Findings regarding changes in the circulating levels of soluble interleukin-6 receptor (sIL6R) in schizophrenia have been equivocal. The study was performed on a group of 147 trio (patients diagnosed with schizophrenia and their healthy parents). Polymorphisms of IL6 (rs1800795, rs1800797) and IL6R (rs4537545, rs4845617, rs2228145) genes were genotyped with the use of TaqMan SNP Genotyping Assays. No association of the polymorphisms from IL6 and IL6R genes with schizophrenia was found. We also investigated haplotypes in IL6 gene (consisting of rs1800795 and rs1800797) and in IL6R gene (consisting of rs4537545, rs2228145). We also found no preference in transmission of any haplotype. Our results do not support the theory that polymorphisms of IL6 and IL6R genes are involved in the pathogenesis of schizophrenia. It seems advisable to carry out further examinations of the role of these polymorphisms in schizophrenia by means of TDT method and classical (case-control) association method.

  1. Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of MMP-9-expressing dendritic cells.

    Science.gov (United States)

    Pahne-Zeppenfeld, Jennifer; Schröer, Nadine; Walch-Rückheim, Barbara; Oldak, Monika; Gorter, Arko; Hegde, Subramanya; Smola, Sigrun

    2014-05-01

    Cervical carcinogenesis is a consequence of persistent infection with high-risk human papillomaviruses (HPVs). Recent studies indicate that HPV-transformed cells actively instruct their microenvironment to promote carcinogenesis. Here, we demonstrate that cervical cancer cells activate monocytes to produce their own CCL2 for further monocyte recruitment and reprogram their function during differentiation and maturation to dendritic cells (DCs). Our data show that cervical cancer cells suppress the induction of the chemokine receptor CCR7 in phenotypically mature DCs and impair their migration toward a lymph node homing chemokine, required to initiate adaptive immune responses. We confirmed the presence of CD83(+)CCR7(low) DCs in cancer biopsies. The second factor essential for DC migration, matrix-metalloproteinase MMP-9, which also has vasculogenic and protumorigenic properties, is not suppressed but upregulated in immature as well as mature DCs. We identified interleukin-6 (IL-6) as a crucial cervical cancer cell-derived mediator and nuclear factor kappaB (NF-jB) as the central signaling pathway targeted in DCs. Anti-IL-6 antibodies reverted not only NF-jB inhibition and restored CCR7-dependent migration but also blocked MMP-9 induction. This is the first report demonstrating the dissociation of CCR7 and MMP-9 expression in phenotypically mature CD83(+) DCs by cancer cells. Our results show that cervical cancer cells actively shape the local microenvironment. They induce the accumulation of myeloid cells and skew their function from immune activation to local production of protumorigenic MMP-9. Neutralizing anti-IL-6 antibodies can counteract this functional dysbalance and should therefore be considered for adjuvant cervical cancer therapy.

  2. Tumor necrosis factor-alpha inhibitor treatment for sarcoidosis

    Directory of Open Access Journals (Sweden)

    José Luis Callejas-Rubio

    2008-12-01

    Full Text Available José Luis Callejas-Rubio, Lourdes López-Pérez, Norberto Ortego-CentenoUnit of Autoimmune Systemic Diseases, Hospital Clinico San Cecilio, Granada, SpainAbstract: Sarcoidosis is a chronic multisystem disease of unknown etiology, characterized by noncaseating granulomatous infiltration of virtually any organ system. Treatment is often undertaken in an attempt to resolve symptoms or prevent progression to organ failure. Previous studies have suggested a prominent role for tumor necrosis factor-alpha (TNF-α in the inflammatory process seen in sarcoidosis. TNF-α and interleukin-1 are released by alveolar macrophages in patients with active lung disease. Corticosteroids have proved to be efficacious in the treatment of sarcoidosis, possibly by suppressing the production of TNF-α and other cytokines. Three agents are currently available as specific TNF antagonists: etanercept, infliximab, and adalimumab. Although data from noncomparative trials suggest that all three have comparable therapeutic effects in rheumatoid arthritis, their effects in a granulomatous disease such as sarcoidosis are less consistent. In this review, current data on the effectiveness are summarized.Keywords: sarcoidosis, infliximab, etanercept, adalimumab, anti-TNA alpha

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

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    Misato Hashizume

    2011-01-01

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

  4. Inhibition of interleukin-6 function attenuates the central sensitization and pain behavior induced by osteoarthritis.

    Science.gov (United States)

    Lin, Yuangui; Liu, Lian; Jiang, Haixia; Zhou, Jieshu; Tang, Yuying

    2017-09-15

    Chronic pain is the most prominent and disabling symptom in the patients with osteoarthritis (OA), and the underlying mechanism largely remains unclear. Interleukin-6 (IL-6), a proinflammatory cytokine, is critically involved in the development and maintenance of central sensitization in several rodent models of chronic pain. The present study aims to elucidate the IL-6 mediated neurological adaptation in dorsal horn in the rat with monosodium iodoacetate (MIA) - induced OA. Significant upregulation of IL-6 expression was detected in the dorsal horn in the modeled rats. Blockade of IL-6 function by tocilizumab markedly suppressed the activation of astrocytes and microglia in the ipsilateral dorsal horn, reduced c-Fos immunoreactivity in dorsal horn neurons, and attenuated the upregulation of glutamate receptor subunits GluR1 and NR2B in dorsal horn in the rats with MIA-induced OA. It was further reported that administration of tocilizumab significantly improved the performance in weight-bearing test and mitigated the mechanical allodynia in the modeled rats. These data illustrated spinal IL-6 mediated mechanism underlying the chronic pain, and proposed the potential therapeutic effect of tocilizumab on the chronic pain in the setting of OA. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Effects of cell type and culture media on Interleukin-6 secretion in response to environmental particles.

    Science.gov (United States)

    Veranth, John M; Cutler, N Shane; Kaser, Erin G; Reilly, Christopher A; Yost, Garold S

    2008-03-01

    Cultured lung cells provide an alternative to animal exposures for comparing the effects of different types of air pollution particles. Studies of particulate matter in vitro have reported proinflammatory cytokine signaling in response to many types of environmental particles, but there have been few studies comparing identical treatments in multiple cell types or identical cells with alternative cell culture protocols. We compared soil-derived, diesel, coal fly ash, titanium dioxide, and kaolin particles along with soluble vanadium and lipopolysaccharide, applied to airway-derived cells grown in submerged culture. Cell types included A549, BEAS-2B, RAW 264.7, and primary macrophages. The cell culture models (specific combinations of cell types and culture conditions) were reproducibly different in the cytokine signaling responses to the suite of treatments. Further, Interleukin-6 (IL-6) response to the treatments changed when the same cells, BEAS-2B, were grown in KGM versus LHC-9 media or in media containing bovine serum. The effect of changing media composition was reversible over multiple changes of media type. Other variables tested included culture well size and degree of confluence. The observation that sensitivity of a cell type to environmental agonists can be manipulated by modifying culture conditions suggests a novel approach for studying biochemical mechanisms of particle toxicity.

  6. Effects of cell type and culture media on Interleukin-6 secretion in response to environmental particles

    Energy Technology Data Exchange (ETDEWEB)

    Veranth, J.M.; Cutler, N.S.; Kaser, E.G.; Reilly, C.A.; Yost, G.S. [University of Utah, Salt Lake City, UT (United States)

    2008-03-15

    Cultured lung cells provide an alternative to animal exposures for comparing the effects of different types of air pollution particles. Studies of particulate matter in vitro have reported proinflammatory cytokine signaling in response to many types of environmental particles, but there have been few studies comparing identical treatments in multiple cell types or identical cells with alternative cell culture protocols. We compared soil-derived, diesel, coal fly ash, titanium dioxide, and kaolin particles along with soluble vanadium and lipopolysaccharide, applied to airway-derived cells grown in submerged culture. Cell types included A549, BEAS-2B, RAW 264.7, and primary macrophages. The cell culture models (specific combinations of cell types and culture conditions) were reproducibly different in the cytokine signaling responses to the suite of treatments. Further, Interleukin-6 (IL-6) response to the treatments changed when the same cells, BEAS-2B, were grown in KGM versus LHC-9 media or in media containing bovine serum. The effect of changing media composition was reversible over multiple changes of media type. Other variables tested included culture well size and degree of confluence. The observation that sensitivity of a cell type to environmental agonists can be manipulated by modifying culture conditions suggests a novel approach for studying biochemical mechanisms of particle toxicity.

  7. Effect of topiramate on interleukin 6 expression in the hippocampus of amygdala-kindled epileptic rats

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    YE, FEI; CHEN, XU-QIN; BAO, GUAN-SHUI; HUA, YIN; WANG, ZHE-DONG; BAO, YI-CHUAN

    2014-01-01

    The objective of this study was to analyze the changes in expression and the possible functions of interleukin-6 (IL-6) in electrical kindling of the basolateral amygdala (BLA) in epileptic rats. Bipolar electrodes were implanted into the BLA of Sprague-Dawley rats, and the rats were then subjected to chronic electrical stimulation through the electrodes to induce kindling. The seizure characteristics and behavioral changes of the rats were observed, and electroencephalograms were recorded during and following kindling. The IL-6 mRNA expression in the hippocampi of the rats was analyzed using semi-quantitative reverse transcription-polymerase chain reaction, and control and topiramate (TPM)-treated groups were compared. The mean time-period required for kindling was 13.50±3.99 days, and the afterdischarge duration (ADD) measured between 21,450 and 119,720 msec. The expression of IL-6 mRNA was significantly upregulated in the kindled rats. TPM was able to depress the seizures and decrease the IL-6 level in the kindled rats. In conclusion, IL-6 mRNA was upregulated in the hippocampi of epileptic rats, and IL-6 may have participated in the process of kindling. PMID:24348794

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

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    Anna Bugge

    2012-01-01

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

  9. Mangiferin regulates interleukin-6 and cystathionine-b-synthase in lipopolysaccharide-induced brain injury.

    Science.gov (United States)

    Fu, Yan-Yan; Zhang, Fang; Zhang, Lei; Liu, Hong-Zhi; Zhao, Zi-Ming; Wen, Xiang-Ru; Wu, Jian; Qi, Da-Shi; Sun, Ying; Du, Yang; Dong, Hong-Yan; Liu, Yong-Hai; Song, Yuan-Jian

    2014-07-01

    Mangiferin has been extensively applied in different fields due to its anti-inflammatory properties. However, the precise mechanism used by mangiferin on lipopolysaccharide (LPS)-induced inflammation has not been elucidated. Here, we discuss the potential mechanism of mangiferin during a LPS-induced brain injury. Brain injury was induced in ICR mice via intraperitoneal LPS injection (5 mg/kg). Open- and closed-field tests were used to detect the behaviors of mice, while immunoblotting was performed to measure the expression of interleukin-6 (IL-6) and cystathionine-b-synthase (CBS) in the hippocampus after mangiferin was orally administered (p.o.). Mangiferin relieved LPS-induced sickness 6 and 24 h after LPS injection; in addition, this compound suppressed LPS-induced IL-6 production after 24 h of LPS induction as well as the downregulation of LPS-induced CBS expression after 6 and 24 h of LPS treatment in the hippocampus. Therefore, mangiferin attenuated sickness behavior by regulating the expression of IL-6 and CBS.

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

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    Min Yang

    2013-01-01

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

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

    DEFF Research Database (Denmark)

    Fosgerau, K; Galle, P; Hansen, Torben

    2010-01-01

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

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

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    P R Ganesh

    2016-01-01

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

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

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    Sven Kruspe

    2014-01-01

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

  14. Interleukin-6 promoter polymorphisms (-174 G/C in Malaysian patients with systemic lupus erythematosus

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    K.H. Chua

    2009-06-01

    Full Text Available Systemic lupus erythematosus (SLE is a chronic autoimmune disease that involves the inflammation of various organs upon deposition of immune complexes and is characterized by uncontrolled B cell hyperactivity. Despite intensive research on the etiology of the disease, the exact cause of the onset of SLE is unknown. The pathogenesis of the disease has been proposed to be associated with the imbalance of T helper type 1 (Th1 and Th2 cytokine activities. Elevated serum levels of interleukin-6 (IL-6, a Th2 cytokine with various functions in the regulation of human biological systems, are observed in SLE patients. In the present study, 100 Malaysian SLE patients and 100 controls were evaluated in order to determine the association of polymorphisms existing in the promoter region of the IL-6 gene with the onset of SLE. The homozygous G genotype was found to be significant in SLE patients (χ² = 33.754; P = 0.00000000625, whereas the heterozygous G/C genotype was significant in the controls (χ²= 25.087; P = 0.000000548. We suggest that the C allele might have a masking effect on the G allele when both alleles are present in heterozygous individuals. However, we did not observe any significant association of the homozygous C allele with the onset of SLE or with protection from the disease (χ² = 1.684; P = 0.194366.

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

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    Paschalina Goutoudi

    2012-01-01

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

  16. Interleukin-6 Receptor Polymorphisms Contribute to the Neurological Status of Korean Patients with Ischemic Stroke

    Science.gov (United States)

    Yoo, Seung Don; Chon, Jinmann; Yun, Dong Hwan; Kim, Hee-Sang; Park, Hae Jeong; Kim, Su Kang; Chung, Joo-Ho; Kang, Jin Kyu

    2016-01-01

    To investigate the contribution of the interleukin-6 receptor (IL-6R) gene single nucleotide polymorphisms (SNPs) to the neurological status of Korean patients with ischemic stroke (IS), two SNPs of the IL-6R gene (rs4845617, 5 UTR; rs2228144, Ala31Ala) were selected. IS patients were classified into clinical phenotypes according to two well-defined scores: the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index scores. There were 121 IS patients and 291 control subjects. The SNP rs4845617 significantly contributed to the neurological status of patients with IS (P = 0.011 in codominant model 2, P = 0.006 in recessive model, and P = 0.008 in log-additive model). Allele frequencies of rs4845617 and rs2228144 demonstrated no significant difference in IS patients and controls. The AG and GG haplotypes differed between the NIHSS 1 (NIHSS scores < 6) group and the NIHSS 2 (NIHSS scores ≥ 6) group in patients with IS (P = 0.014, P = 0.0024). These results suggest that rs4845617 of the IL-6R gene is associated with the neurologic status of Korean patients with IS. PMID:26955245

  17. Changes in interleukin-6 levels during electroconvulsive therapy may reflect the therapeutic response in major depression.

    Science.gov (United States)

    Järventausta, K; Sorri, A; Kampman, O; Björkqvist, M; Tuohimaa, K; Hämäläinen, M; Moilanen, E; Leinonen, E; Peltola, J; Lehtimäki, K

    2017-01-01

    Interleukin-6 (IL-6) has been reported to be elevated in major depressive disorder (MDD) but decreased by antidepressive medication. IL-6 levels are markedly elevated both after epileptic seizures and single electroconvulsive therapy (ECT) session, but long-term changes in IL-6 levels after ECT have not been studied. The correlation between immediate and long-term changes in proinflammatory cytokines and outcome after ECT was investigated. Thirty patients suffering from MDD participated in the study. IL-6, interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1RA) levels were examined at baseline and at 2 and 4 h after the first, fifth and the last ECT sessions. The response to ECT was measured with Montgomery-Åsberg Depression Rating Scale (MADRS). ECT repeatedly caused an increase in IL-6 levels at the 4-h time point. However, the baseline IL-6 levels decreased among remitters, but not among non-remitters, towards the end of ECT. IL-1β levels were mostly below detectable level, and IL-1Ra levels did not change during and after ECT. ECT has distinct acute and long-term effects on IL-6 levels. Interestingly, the long-term effect of ECT on IL-6 seems to correlate with outcome, providing further evidence of the mechanism of action of ECT and supporting the inflammation theory in MDD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Openness and conscientiousness predict 34-week patterns of Interleukin-6 in older persons.

    Science.gov (United States)

    Chapman, Benjamin P; van Wijngaarden, Edwin; Seplaki, Christopher L; Talbot, Nancy; Duberstein, Paul; Moynihan, Jan

    2011-05-01

    Studies have indicated that personality may be associated with inflammatory markers such as Interleukin (IL)-6. One pathway between personality and IL-6 may be health behaviors and conditions resulting in inflammation, while an alternate pathway involves activation of stress-response systems. In a clinical trial sample of 200 older adults, we examined associations between personality traits at baseline and three measures of IL-6 spanning 34 weeks of follow-up. Results indicate that IL-6 remained very stable over time, and that higher Conscientiousness and Openness were associated with lower IL-6 across the entire 34 week period. Goal striving was the active subcomponent of Conscientiousness, while aesthetic interests was the active subcomponent of Openness in IL-6 associations. Common health behaviors and chronic illness accounted for only a portion of these effects, suggesting that other behavioral and/or physiological processes may also predispose some persons to inflammation. Personality phenotype may provide useful prognostic information for inflammation. Older adults lower in Conscientiousness and Openness constitute a target population for anti-inflammatory interventions. Openness and Conscientiousness predicts 32-week patterns of Interleukin-6 in older persons.

  19. Association of interleukin-6 polymorphisms with obesity and metabolic alterations in young Saudi population.

    Science.gov (United States)

    Alharbi, Khalid Khalaf; Syed, Rabbani; Khan, Imran Ali

    2014-03-01

    Rising levels of obesity are a global problem that is being exported from affluent to developing nations through the gradual "westernization of lifestyle". Population of Saudi Arabia is going through a nutrition transition where customary and traditional food is being replaced by fast food high in fat, sugar and salt. Interleukin-6 (IL-6) is a central player in the regulation of inflammation, haematopoiesis, immune response and host defense mechanisms. During the last decade, an accumulating amount of data suggested a pivotal role for IL-6 in metabolic processes, thus fortifying the picture of IL-6 as a multifaceted, pleiotropic cytokine. The Objective is to investigate the relationship between IL-6 (rs1554606) polymorphism and the risk of obesity in young Saudi population. Totally 204 Saudi young obese subjects were involved in this study. Genotyping of IL-6 was performed by the real-time polymerase chain reaction technology, using the Taq Man 5'-allele discrimination assay. IL-6 (rs1554606) AA versus AG (p 0.5). We have observed significant effects for Genotyping, LDL, CHOL, AST, ALP, BILIT, BMI at 5% (0.05) significance level in the study population. Our results shown that IL-6 polymorphism have significantly differ in both male and females subjects. We have observed that some evidence of interactions of the IL-6 polymorphism and have shown statistical significant association with elevated BMI, Lipid profile and total bilurubin in the study subjects.

  20. Interleukin-6 and highly sensitive C-reactive protein in obese adolescents

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    Michael Kasenda

    2012-07-01

    Full Text Available Background Childhood obesity is a major health concern. Oobesity is due to an expansion of adipose tissue mass. This tissue produces pro-inflammatory cytokines, such as interleukin-6 (IL-6. IL-6 is considered to be the chief stimulator of the production of highly sensitive C-reactive protein (hsCRP in the liver. Both molecules are responsible for the chronic low-grade inflammatory state in obese individuals. Objective To assess a correlation between IL-6 and hsCRP in obese adolescents. Methods This cross-sectional study was conducted from March to June 2011 in Manado. Subjects were obese and normal body mass index (BMI teens aged 13-18 years. Serum glutamic oxaloacetic transaminase (SGOT and serum glutamic pyruvic transaminase (SGPT levels were measured to rule out liver impairment. IL-6 and hsCRP levels were also measured. Data was analyzed by Pearson’s correlation and linear regression to test for correlation between IL-6 and hsCRP levels. Results There was a strongly positive correlation between IL-6 and hsCRP levels in obese adolescents (r=0.79 with P<0.001. IL-6 and hsCRP levels were not significantly associated in subjects with normal BMI. Conclusions There was a strongly positive correlation between IL-6 and hsCRP levels in obese adolescents, suggestive of an ongoing, chronic, low-grade inflammatory state.

  1. Interleukin 6 SNP rs1800797 associates with the risk of adult-onset asthma.

    Science.gov (United States)

    Lajunen, T K; Jaakkola, J J K; Jaakkola, M S

    2016-04-01

    Interleukin 6 (IL6) is an inflammatory cytokine that has been suggested to have an important role in the pathogenesis of asthma. IL6 single-nucleotide polymorphisms (SNPs) have been associated with levels of IL6, and with childhood and prevalent adult asthma. A recent study also suggested that IL6 SNPs associate especially with atopic asthma. However, association of IL6 SNPs with adult-onset asthma has not been studied. In a population-based study of 467 incident adult-onset asthma cases and 613 disease-free controls from South Finland, we analyzed association of 6 tagging SNPs of the IL6 locus with the risk of adult-onset asthma and with atopy. Asthma was clinically diagnosed, and atopy was defined based on Phadiatop test. IL6 SNP rs1800797 associated with the risk of adult-onset asthma in a log additive model, with adjusted odds ratio (aOR) 1.31 (95% confidence interval 1.09-1.57), and especially with the risk of atopic adult-onset asthma when compared with non-atopic controls, aOR 1.46 (95% CI 1.12-1.90). This is the first study to show an association of IL6 with adult-onset asthma, and especially with atopic adult-onset asthma.

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

    Science.gov (United States)

    Zhou, Zhou; Nair, Muraleedharan G; Claycombe, Kate J

    2012-07-15

    Studies have shown positive correlations between inflammatory cytokines such as interleukin-6 (IL-6) and the development of chronic diseases including cardiovascular disease by activating C-reactive protein (CRP). Both atorvastatin calcium (lipitor) as well as flavonoid rich fruit such as tart cherry demonstrate potent anti-inflammatory effects on IL-6 secretion. In this study, we investigated whether tart cherry extract or specific anthocyanins contained in the tart cherry show synergistic anti-inflammatory effects with lipitor. Results showed that LPS-induced adipose stem cell secretion of IL-6 reduced with the addition of tart cherry extract, a mixture of tart cherry anthocyanins, and pure tart cherry cyanidin-3-O-glucoside (C3G) in a dose-dependent manner. Furthermore, lipitor and C3G exhibited synergistic effects in reducing LPS-induced IL-6 secretion from adipose stem cells. In conclusion, these results support potential benefits of using dietary phytochemicals in conjunction with pharmacological therapies to decrease adipose inflammation, drug doses, and ultimately, drug-induced adverse effects.

  3. Big 5 personality traits and interleukin-6: evidence for "healthy Neuroticism" in a US population sample.

    Science.gov (United States)

    Turiano, Nicholas A; Mroczek, Daniel K; Moynihan, Jan; Chapman, Benjamin P

    2013-02-01

    The current study investigated if the Big 5 personality traits predicted interleukin-6 (IL-6) levels in a national sample over the course of 5years. In addition, interactions among the Big 5 were tested to provide a more accurate understanding of how personality traits may influence an inflammatory biomarker. Data included 1054 participants in the Midlife Development in the U.S. (MIDUS) biomarkers subproject. The Big 5 personality traits were assessed in 2005-2006 as part of the main MIDUS survey. Medication use, comorbid conditions, smoking behavior, alcohol use, body mass index, and serum levels of IL-6 were assessed in 2005-2009 as part of the biomarkers subproject. Linear regression analyses examined personality associations with IL-6. A significant Conscientiousness*Neuroticism interaction revealed that those high in both Conscientiousness and Neuroticism had lower circulating IL-6 levels than people with all other configurations of Conscientiousness and Neuroticism. Adjustment for health behaviors diminished the magnitude of this association but did not eliminate it, suggesting that lower comorbid conditions and obesity may partly explain the lower inflammation of those high in both Conscientiousness and Neuroticism. Our findings suggest, consistent with prior speculation, that average to higher levels of Neuroticism can in some cases be associated with health benefits - in this case when it is accompanied by high Conscientiousness. Using personality to identify those at risk may lead to greater personalization in the prevention and remediation of chronic inflammation.

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

    Science.gov (United States)

    Penkowa, Milena; Keller, Charlotte; Keller, Pernille; Jauffred, Sune; Pedersen, Bente Klarlund

    2003-11-01

    Interleukin-6 (IL-6) is produced by many different cell types. Human skeletal muscles produce and release high amounts of IL-6 during exercise; however, the cell source of origin in the muscle is not known. Therefore, we studied the protein expression of IL-6 by immunohistochemistry in human muscle tissue from biopsies obtained at time points 0, 3, 4.5, 6, 9, and 24 h in relation to 3 h of bicycle exercise performed by healthy young males (n=12) and in resting controls (n=6). The IL-6 expression was clearly increased after exercise and remained high even by 24 h, relative to pre-exercise or resting individuals. The IL-6 immunostainings of skeletal muscle cells were homogeneous and without difference between muscle fiber types. The IL-6 mRNA peaked immediately after the exercise, and, in accordance, the IL-6 protein expression within muscle cells was most pronounced around 3 h post-exercise. However, the finding that plasma IL-6 concentration peaked in the end of exercise indicates a high turnover of muscle-derived IL-6. In conclusion, the finding of marked IL-6 protein expression exclusively within skeletal muscle fibers following exercise demonstrates that skeletal muscle fibers of all types are the dominant cell source of exercise-induced release of IL-6 from working muscle.

  5. Inhibition of the interleukin-6 signaling pathway: a strategy to induce immune tolerance.

    Science.gov (United States)

    Zhang, Cheng; Zhang, Xi; Chen, Xing-Hua

    2014-10-01

    Interleukin-6 (IL-6) is a proinflammatory cytokine that is multifunctional, with multifaceted effects. IL-6 signaling plays a vital role in the control of the differentiation and activation of T lymphocytes by inducing different pathways. In particular, IL-6 controls the balance between Th17 cells and regulatory T (Treg) cells. An imbalance between Treg and Th17 cells is thought to play a pathological role in various immune-mediated diseases. Deregulated IL-6 production and signaling are associated with immune tolerance. Therefore, methods of inhibiting IL-6 production, receptors, and signaling pathways are strategies that are currently being widely pursued to develop novel therapies that induce immune tolerance. This survey aims to provide an updated account of why IL-6 inhibitors are becoming a vital class of drugs that are potentially useful for inducing immune tolerance as a treatment for autoimmune diseases and transplant rejection. In addition, we discuss the effect of targeting IL-6 in recent experimental and clinical studies on autoimmune diseases and transplant rejection.

  6. Dietary Iron Intake and Serum Interleukin-6 Levels of Obese Children With and Without Iron Deficiency

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    Lanang Sidiartha

    2016-07-01

    Full Text Available Background: Iron deficiency is more common in obese children. Low dietary iron intake and inflammation are suspected as the cause. This study investigates the dietary iron intake and serum IL-6 levels relationship with the obese children iron status. Methods: Seventy obese children were recruited. Dietary iron intake was calculated using three days’ food record. Serum IL-6 was measured using sandwich ELISA. Iron deficiency was confirmed if iron serum <60 mcg/dl and/or saturation of transferrin <20%. Independent t-test was used to analyze the mean difference of the dietary iron intake between the with and without iron deficiency groups, α=0.05. And, Mann-Whitney for the median difference of the serum IL-6 between the two groups. Results: Forty-six subjects (65.7% had iron deficiency. Dietary iron intake of the with and without iron deficiency groups were 6.8 mg (SD 3.3 and 6.6 mg (SD 3.8, respectively (p>0.05. The interleukin-6 was 2.7 pg/ml (0.3-16.8 and 1.7 pg/ml (0.8-4.9, respectively (p<0.05. Conclusion: Iron deficiency in obese children was high. It was not associated with low dietary iron intake, but associated with inflammation.

  7. Increased serum levels of interleukin 6 are associated with severe intraventricular haemorrhage in extremely premature infants

    Science.gov (United States)

    Heep, A; Behrendt, D; Nitsch, P; Fimmers, R; Bartmann, P; Dembinski, J

    2003-01-01

    Background: Intraventricular haemorrhage (IVH) and periventricular leucomalacia (PVL) in premature infants presumably have many causes. It has been proposed that inflammatory processes in the fetomaternal unit play an important role in the pathogenesis of these lesions. Objective: To study the correlation of postpartum serum interleukin 6 (IL6) concentration as a marker of inflammation and neonatal cerebral morbidity in preterm infants 100 pg/ml. Ultrasound studies and clinical assessment were performed routinely. Results: IVH was noted significantly more often in group B (24/38; 63%) than in group A (19/50; 38%) (p = 0.02). In a multiple logistic regression model, raised serum IL6 independently predicted development of severe IVH (odds ratio 8.4; 95% confidence interval 2.85 to 24.9; p = 0.0001). Conclusions: Raised serum IL6 may serve as a marker for severe IVH in infants < 28 weeks of gestational age. Although cerebral morbidity in premature infants is determined by different variables, the identification of systemic inflammation can help to define the need for anti-inflammatory strategies to prevent cerebral morbidity. PMID:14602698

  8. Association among interleukin-6 gene polymorphisms, type 2 diabetes mellitus, and chronic periodontitis: a pilot study.

    Science.gov (United States)

    Kavitha, Loganathan; Vijayshree Priyadharshini, Jayaseelan; Sivapathasundharam, Balasundaram

    2017-08-01

    The purpose of this pilot study was to determine the association between single nucleotide polymorphisms (-174 G>C) in the interleukin-6 (IL-6) gene with chronic periodontitis (CP) and type 2 diabetes mellitus (T2DM) in south Indian population. Genomic DNA was obtained from the white blood cells of 30 patients with T2DM, 30 patients with CP, 30 patients with T2DM with CP, and 30 controls. DNA was amplified using polymerase chain reaction with specific primers flanking the locus -174 of the IL-6 gene and further genotyped using the restriction fragment length polymorphism method. The genotype distribution and allele frequencies between the study groups were determined using χ(2) -test. The relative risk was estimated with a 95% confidence interval. The CP group (26.7%) displayed a greater percentage of GC genotype (P = 0.026) when compared to the control group (3.3%). A statistically-significant difference in the allele frequencies was found between the control and CP group with the C-allele frequency being greater (0.13) in the CP group than normal controls (0.02). The GC genotype was found to be the risk genotype and the C allele was found to be the risk allele for the development of CP. © 2016 John Wiley & Sons Australia, Ltd.

  9. Adipocyte lipolysis-stimulated interleukin-6 production requires sphingosine kinase 1 activity.

    Science.gov (United States)

    Zhang, Wenliang; Mottillo, Emilio P; Zhao, Jiawei; Gartung, Allison; VanHecke, Garrett C; Lee, Jen-Fu; Maddipati, Krishna R; Xu, Haiyan; Ahn, Young-Hoon; Proia, Richard L; Granneman, James G; Lee, Menq-Jer

    2014-11-14

    Adipocyte lipolysis can increase the production of inflammatory cytokines such as interleukin-6 (IL-6) that promote insulin resistance. However, the mechanisms that link lipolysis with inflammation remain elusive. Acute activation of β3-adrenergic receptors (ADRB3) triggers lipolysis and up-regulates production of IL-6 in adipocytes, and both of these effects are blocked by pharmacological inhibition of hormone-sensitive lipase. We report that stimulation of ADRB3 induces expression of sphingosine kinase 1 (SphK1) and increases sphingosine 1-phosphate production in adipocytes in a manner that also depends on hormone-sensitive lipase activity. Mechanistically, we found that adipose lipolysis-induced SphK1 up-regulation is mediated by the c-Jun N-terminal kinase (JNK)/activating protein-1 signaling pathway. Inhibition of SphK1 by sphingosine kinase inhibitor 2 diminished the ADRB3-induced IL-6 production both in vitro and in vivo. Induction of IL-6 by ADRB3 activation was suppressed by siRNA knockdown of Sphk1 in cultured adipocytes and was severely attenuated in Sphk1 null mice. Conversely, ectopic expression of SphK1 increased IL-6 expression in adipocytes. Collectively, these data demonstrate that SphK1 is a critical mediator in lipolysis-triggered inflammation in adipocytes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Influence of fluvoxamine on plasma interleukin-6 or clinical improvement in patients with major depressive disorder

    Science.gov (United States)

    Yoshimura, Reiji; Katsuki, Asuka; Atake, Kiyokazu; Hori, Hikaru; Igata, Ryohei; Konishi, Yuki

    2017-01-01

    Objectives The etiology of depression remains unknown. There is, however, a growing body of evidence that cytokines are involved in the pathophysiology of depression. The aim of this study is to investigate the effects of fluvoxamine on plasma interleukin-6 (IL-6) levels and on clinical improvement of the depressive state. Subjects and methods Thirty patients who met the DSM-IV criteria for major depressive disorder (MDD) were enrolled in the study. Thirteen were male and 17 were female, and their ages ranged from 26 to 70 years (mean ± standard deviation 45.0±14.2). The patients were treated with fluvoxamine for 8 weeks. The dosages of fluvoxamine varied among the patients and, based on ethical considerations, were not fixed. Results The fluvoxamine doses were positively related to plasma fluvoxamine levels (r =0.8798, P<0.001). A significant correlation was observed between the patients’ plasma IL-6 levels and their 17-item Hamilton Rating Scale for Depression (HAMD17) scores (r =0.4555, P=0.0010). A positive correlation was found between the delta plasma IL-6 (week 0–week 8) and the delta HAMD17 (week 0–week 8) (r =0.5226, P=0.002). Conclusion Effect of fluvoxamine on IL-6 is partially associated with its clinical efficacy for MDD. PMID:28243095

  11. Interleukin-6 impairs chronotropic responsiveness to cholinergic stimulation and decreases heart rate variability in mice.

    Science.gov (United States)

    Hajiasgharzadeh, Khalil; Mirnajafi-Zadeh, Javad; Mani, Ali R

    2011-12-30

    Heart rate variability is reduced in several clinical settings associated with systemic inflammation. The underlying mechanism of decreased heart rate variability during systemic inflammation is unknown. It appears that the inflammatory cytokines might play a role, since epidemiologic studies has shown that circulating levels of interleukine-6 (IL-6) correlate significantly with indexes of depressed heart rate variability in various clinical conditions. The present investigation was carried out to study the peripheral and central effects of IL-6 on heart rate dynamic in mice. Adult male BALB/c mice were used in the study. RT-PCR was performed to study the expression of IL-6 receptor in mouse atrial and the results showed that gp130 mRNA was detectable in the atrium. The effect of IL-6 was also studies on chronotropic responsiveness of isolated atria to adrenergic and cholinergic stimulations. Incubation of isolated atria with 10 ng/ml of IL-6 was associated with a significant hypo-responsiveness to cholinergic stimulation (log IC₅₀ of carbacholine changed from -6.26±0.10 in controls to -5.59±0.19 following incubation with IL-6, Pheart rate variability parameters (SDNN, SD1, and SD2). While intracerebroventricular injection of IL-6 (50 ng/mouse) had no significant effect on heart rate variability parameters. These data are in line with a peripheral role for IL-6 in the genesis of decreased heart rate variability during systemic inflammation.

  12. Lower subjective social status exaggerates interleukin-6 responses to a laboratory stressor.

    Science.gov (United States)

    Derry, Heather M; Fagundes, Christopher P; Andridge, Rebecca; Glaser, Ronald; Malarkey, William B; Kiecolt-Glaser, Janice K

    2013-11-01

    Growing evidence suggests that lower subjective social status (SSS), which reflects where a person positions himself on a social ladder in relation to others, is independently related to poor health. People who rate themselves lower in status also experience more frequent stressors and report higher stress than those who rate themselves higher in status, and chronic stress can enhance an individual's response to subsequent stressors. To address whether SSS predicted stress-induced interleukin-6 (IL-6) changes, we assessed 138 healthy adults at rest and following the Trier Social Stress Test (TSST). Participants completed the TSST at two study visits, separated by 4 months. People who placed themselves lower on the social ladder had larger IL-6 responses from baseline to 45 min post-stressor (p=0.01) and from baseline to 2h post-stressor (p=0.03) than those who placed themselves higher on the social ladder. Based on a ratio of subjective threat and coping ratings of the stress task, participants who viewed themselves as lower in status also tended to rate the speech task as more threatening and less manageable than those who viewed themselves as higher in status (p=0.05). These data suggest that people with lower perceived status experience greater physiological and psychological burden from brief stressors compared to those with higher perceived status. Accordingly, responses to stressors may be a possible mechanistic link among SSS, stress, and health.

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

    DEFF Research Database (Denmark)

    Molinero, Amalia; Penkowa, Milena; Hernández, Joaquín;

    2003-01-01

    Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP-IL6 mice) causes significant damage and alters the expression of many genes, including a dramatic upregulation of metallothionein-I (MT-I). The findings in ...

  14. Regulatory effect of miR-149 on interleukin-6 expression in silica-induced pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    范晶晶

    2014-01-01

    Objective To investigate the regulatory effect of miR-149 on interleukin-6(IL-6)expression in silica-induced pulmonary fibrosis.Methods A mouse model of pulmonary fibrosis was established using silica dust;the level of miR-149 in the lung tissues of mice with silicainduced pulmonary fibrosis was measured by quantitative

  15. Anemia in diffuse large B-cell non-Hodgkin lymphoma: the role of interleukin-6, hepcidin and erythropoietin

    NARCIS (Netherlands)

    Tisi, M.C.; Bozzoli, V.; Giachelia, M.; Massini, G.; Ricerca, B.M.; Maiolo, E.; D'Alo, F.; Larocca, L.M.; Piciocchi, A.; Tjalsma, H.; Swinkels, D.W.; Voso, M.T.; Leone, G.; Hohaus, S.

    2014-01-01

    Anemia is a frequent sign in patients with diffuse large B-cell lymphoma (DLBCL) at diagnosis. We determined erythropoietin, hepcidin and interleukin-6 (IL-6) in plasma samples of 53 patients with DLBCL. The majority of patients (40/53, 75%) showed defective endogenous erythropoietin production, in

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  17. INTERLEUKIN-6 AND ITS RELATION TO THE HUMORAL IMMUNE-RESPONSE AND CLINICAL-PARAMETERS IN BURNED PATIENTS

    NARCIS (Netherlands)

    NIJSTEN, MWN; HACK, CE; HELLE, M; TENDUIS, HJ; KLASEN, HJ; AARDEN, LA

    1991-01-01

    The cytokine interleukin-6, which has been shown to be increased in patients with burn injuries, is produced by activated monocytes and endothelial cells and has many in vitro activities, including stimulation of acute-phase protein synthesis in hepatocytes, immunoglobulin synthesis in B lymphocytes

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

    Directory of Open Access Journals (Sweden)

    Omoigui Sota

    2007-03-01

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

  19. [The effect of tumor necrosis factor alpha on hepatic necrosis in viral hepatitis].

    Science.gov (United States)

    Yu, Y; Si, C; Lang, Z

    1996-01-01

    In order to investigate the effect of tumor necrosis factor alpha (TNF alpha) on hepatocyte necrosis in viral hepatitis, TNF alpha with or without D-galactosamine (D-Gal) was injected into the abdominal cavity of rats. No effect was observed after injection of TNF alpha alone. After injection of TNF alpha with D-Gal, the total bilirubin level in rat blood increased and hepatocyte necrosis appeared (P hepatic tissue were stained with anti-TNF alpha McAb by using ABC immunohistochemistry method. It was found that more severe the hepatocyte necrosis, more the positive cells expressing TNF alpha. There were more TNF alpha positive cells in the tissue of severe hepatitis. These results suggested that TNF alpha is a mediator in hepatocyte necrosis.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Class A Scavenger Receptor Exacerbates Osteoclastogenesis by an Interleukin-6-Mediated Mechanism through ERK and JNK Signaling Pathways

    Science.gov (United States)

    Guo, Shuyu; Ni, Yuanyuan; Ben, Jingjing; Xia, Yang; Zhou, Tingting; Wang, Dongyue; Ni, Jieli; Bai, Hui; Wang, Lin; Ma, Junqing; Chen, Qi

    2016-01-01

    Osteoclasts originate from bone marrow monocyte/macrophage lineage cells, which are important for bone health. Class A scavenger receptor (SR-A) is a multifunctional molecule that functions during differentiation of monocyte into macrophages and osteoclasts. To further characterize the role of SR-A in osteoclasts, we used the murine tooth movement model (TM) and the murine anterior cruciate ligament transection model of osteoarthritis (ACLT OA). In these two models the bones involved are of different origin and have different properties. Bone resorption was decreased in SR-A-/- mice compared to SR-A+/+ mice. Further evaluation showed that the number of multinucleated osteoclasts in SR-A-/- mice, compared to SR-A+/+ mice, was significantly decreased both in vivo and in vitro. The levels of interleukin-6 (IL-6) produced by osteoclasts were reduced in SR-A-/- mice compared to SR-A+/+ mice. In the in vitro marrow-derived osteoclast formation assay and in both mouse models, osteoclastogenesis was restored to normal in SR-A-/- mice by administration of recombinant murine IL-6. Moreover, neutralization of IL-6 reduced the number of osteoclasts formed in SR-A+/+ mice of TM model. Both extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK), but not p38, signaling pathways were downregulated in receptor activator of nuclear factor-κB ligand (RANKL)-stimulated SR-A-/- osteoclasts. Importantly, when treated with either ERK or JNK inhibitor, the numbers of osteoclasts generated from RANKL-induced bone marrow derived-macrophages of SR-A+/+ mice, and their IL-6 production, were significantly decreased. This suggests that SR-A activates the ERK and JNK signaling pathways, and promotes production of IL-6 by osteoclasts to further stimulate osteoclast formation. PMID:27766031

  3. Chemokine stromal cell-derived factor 1alpha activates basophils by means of CXCR4

    DEFF Research Database (Denmark)

    Jinquan, T; Jacobi, H H; Jing, C

    2000-01-01

    The CXC chemokine receptor 4 (CXCR4) is predominantly expressed on inactivated naive T lymphocytes, B lymphocytes, dendritic cells, and endothelial cells. CXC chemokine stromal cell-derived factor 1alpha (SDF-1alpha) is the only known ligand for CXCR4. To date, the CXCR4 expression and function...... of SDF-1alpha in basophils are unknown....

  4. Functional activities of receptors for tumor necrosis factor-alpha on human vascular endothelial cells.

    NARCIS (Netherlands)

    Paleolog, E.M.; Delasalle, S.A.; Buurman, W.A.; Feldmann, M.

    1994-01-01

    Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in the control of endothelial cell function and hence in regulating traffic of circulating cells into tissues in vivo. Stimulation of endothelial cells in vitro by TNF-alpha increases the surface expression of leukocyte adhesion molecules

  5. T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis

    NARCIS (Netherlands)

    van Riemsdijk, I C; Baan, C C; Loonen, E H; Knoop, C J; Navarro Betonico, G; Niesters, H G; Zietse, R; Weimar, W

    2001-01-01

    BACKGROUND: The immunosuppressive state of hemodialysis (HD) patients is accompanied by activation of antigen-presenting cell-derived cytokines, for example, tumor necrosis factor-alpha (TNF-alpha), which are required for T-cell activation. To test whether an activated TNF-alpha system results in im

  6. The role of transforming growth factor alpha in rat craniofacial development and chondrogenesis.

    OpenAIRE

    Huang, L; Solursh, M; Sandra, A

    1996-01-01

    To explore the possible role of transforming growth factor alpha (TGF-alpha) in craniofacial development, its expression in the craniofacial region of rat embryos from embryonic day (d) 9 to d 20 was examined by in situ hybridisation and immunostaining. The TGF-alpha transcripts were first detected in the neural fold of embryonic d 9 and 10 embryos. In the craniofacial region, the TGF-alpha transcripts were not detected until embryonic d 16 in mesenchyme surrounding the olfactory bulb, within...

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

    Directory of Open Access Journals (Sweden)

    Zheng Peng

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

  8. Association between Serum Levels of Interleukin-6 and Stage of Laryngeal Cancer

    Directory of Open Access Journals (Sweden)

    soheila nikakhlagh

    2015-05-01

    Full Text Available Introduction: The purpose of this study was to investigate the relationship between serum levels of interleukin-6 (IL-6 and the severity and extent of squamous cell carcinoma (SCC of the larynx based on stage of tumor progression and histological grade.   Materials and Methods: All patients with a diagnosis of laryngeal cancer who underwent laryngoscopy and biopsy while hospitalized in Imam Khomeini Hospital in Ahvaz were enrolled. Tumor stage was calculated based on the TNM system, and divided into early (stage 1,2 or advanced stage (stage 3,4. In addition, patients were divided into low-grade (well differentiated or high-grade (moderate and poorly differentiated groups based on pathology reports from biopsy specimens. Several healthy volunteers were also enrolled as the control group. After collecting the blood samples, quantitative serum levels of IL-6 were measured (pmol/L using IL-6 kits (Bender MedSystem, Germany. Results for quantitative variables are presented as mean and standard deviation and qualitative variables as percentages. Mann-Whitney, Kruskal-Wallis and Pearson’s chi square tests were used for statistical analyses. Results: Thirty-eight patients (82.6% were male and eight patients (17.4% were female. IL-6 serum level was 28.8±4.7 pmol/L in the patient group and 2.64±2.88 pmol/L in the control group (P=0.0001. The serum level of IL-6 was 7.27 ± 5.31 pmol/L in early-stage patients and 54.43 ± 6.06 pmol/L in advanced-stage patients (P

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

    Science.gov (United States)

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

    2015-01-01

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

  10. Expression of interleukin-6 is downregulated by 17-(allylamino)-17-demethoxygeldanamycin in human prostatic carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Ke-hung TSUI; Tsui-hsia FENG; Wen-chi HSIEH; Phei-lang CHANG; Horng-heng JUANG

    2008-01-01

    Aim: Interleukin-6 (IL-6) is a pleiotropic cytokine that is associated with tumor metastasis and prostate cancer. We evaluated the mechanism and effect of 17-(allylamino)-17-demethoxygeldanamycin (17AAG), a novel inhibitor of heat shock protein 90 (Hsp90), on the IL-6 gene expression in human prostatic carcinoma (PC-3) cells. Methods: Quantitative IL-6 and IL-6 receptor (IL-6R) expressions were assessed using RT-PCR. The deregulation of 17AAG and phor-bol 12-myristate 13-acetate (PMA) on the IL-6 gene was determined by ELISA and transient gene expression assays using an IL-6 reporter vector. Results: Although the IL-6R is ubiquitously expressed by prostatic epithelium cells, the IL-6 expression is only found in advanced prostatic carcinoma cells, such as PC-3 and DU145. Further studies using RT-PCR indicated that 17AAG downregulated the gene expression of IL-6. ELISA and the transient gene expression assay revealed that 17AAG blocked the stimulation of PMA of IL-6 gene expression in PC-3 cells. The PMA-induced IL-6 gene expression is dependent on the NF-κB response element. However, the effect of 17AAG appears to be mediated via a region located at -149 to +8 bp upstream of the transcriptional starting site of the IL-6 gene, and might not be through the NF-κB signaling pathway. Conclusion: The present study reveals that IL-6 is transcriptionally downregulated in human prostatic carcinoma cells in response to 17AAG. This result suggests the presence of a novel Hsp90 mediation pathway that is involved in the deregulation on the transcription of the human IL-6 gene in human prostate cancer.

  11. Hypomethylation of Interleukin-6 Promoter is Associated with the Risk of Coronary Heart Disease

    Science.gov (United States)

    Zuo, Hong-Peng; Guo, Ying-Yu; Che, Lin; Wu, Xian-Zheng

    2016-01-01

    Background: Interleukin-6 (IL-6) is implicated in the pathogenesis of coronary heart disease (CHD), and IL-6 expression has associated with reduced DNA methylation of its gene promoter. However, there are no data on IL-6 promoter methylation and the risk of CHD. Objective: To examine whether IL-6 promoter methylation measured in blood leukocyte DNA is associated with CHD risk. Methods: A total of 212 cases with CHD and 218 controls were enrolled. Methylation at two CpG sites in IL-6 promoter was measured by bisulfite pyrosequencing, and the mean IL-6 methylation was calculated by averaging the methylation measures of the two CpGs. Results: Mean methylation level in IL-6 promoter in CHD cases was significantly lower than that in controls (p = 0.023). Logistic regression analysis showed that IL-6 methylation was inversely associated with the risk of CHD. The odds ratios (ORs) of CHD for subjects in the second and first (lowest) tertile of IL-6 methylation were 1.87 (95% CI = 1.10‑3.20) and 2.01 (95% CI = 1.19-3.38) (ptrend = 0.013), respectively, compared to subjects in the third (highest) tertile. The IL-6 hypomethylation-related risk estimates tended to be stronger for acute myocardial infarction (ptrend = 0.006). CpG position-specific analysis showed that hypomethylation of position 1 conferred a more pronounced increase in CHD risk than that of position 2. Conclusion: These findings suggest that DNA hypomethylation of IL-6 promoter is associated with the increased risk for CHD, especially for acute myocardial infarction. The two distinct CpGs in IL-6 may contribute differently to the development of CHD. PMID:27627640

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

    Directory of Open Access Journals (Sweden)

    Karol Kaminski

    2011-04-01

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

  13. Role of serum interleukin-6 in deciding therapy for multidrug resistant oral lichen planus

    Science.gov (United States)

    Marwah, Akanksha; Kaushik, Smita; Garg, Vijay K.; Gupta, Sunita

    2015-01-01

    Background Oral lichen planus (OLP) is a T cell mediated immune response. T cells locally present in the involved tissues release cytokines like interleukin-6 (IL-6), which contributes to pathogenesis of OLP. Also IL-6 has been associated with multidrug resistance protein (MRP) expression by keratinocytes. Correspondingly, upregulation of MRP was found in OLP. We conducted this study to evaluate the effects of various drugs on serum IL-6 in OLP; and correlation of these effects with the nature of clinical response and resistance pattern seen in OLP lesions with various therapeutic modalities. Thus we evaluated the role of serum IL-6 in deciding therapy for multidrug resistant OLP. Material and Methods Serum IL-6 was evaluated in 42 erosive OLP (EOLP) patients and 10 normal mucosa and 10 oral squamous cell carcinoma cases using ELISA technique. OLP patients were randomly divided into 3 groups of 14 patients each and were subjected to Pimecrolimus local application, oral Mycophenolate Mofetil (MMF) and Methotrexate (MTX) alongwith Pimecrolimus local application. IL-6 levels were evaluated before and after treatment. Results Serum IL-6 levels were raised above 3pg/ml in 26.19% erosive OLP (EOLP) cases (mean- 3.72±8.14). EOLP (5%) cases with IL-6 levels above 5pg/ml were resistant in MTX group. However significant decrease in serum IL-6 corresponding with the clinical resolution was seen in MMF group. Conclusions Significantly raised IL-6 levels in EOLP reflect the chronic inflammatory nature of the disease. As serum IL-6 levels significantly decreased in MMF group, correspondingly no resistance to treatment was noted. However with MTX there was no significant decrease in IL-6 and resistance to treatment was noted in some, especially plaque type lesions. Thus IL-6 can be a possible biomarker in deciding the best possible therapy for treatment resistant OLP. Key words:Lichen planus, biological markers, cytokines, enzyme-linked immunosorbent assay, immunosuppressive

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

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    Lidija Kitanovski

    2004-12-01

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

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

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

    2008-09-15

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

  16. Interleukin-6 as inflammatory marker referring to multiple organ dysfunction syndrome in severely injured children

    Science.gov (United States)

    2014-01-01

    Background Despite the suggestion that the inflammatory response in traumatized children is functionally unique, prognostic markers predicting pediatric multiple organ failure are lacking. We intended to verify whether Interleukin-6 (IL-6) displays a pivotal role in pediatric trauma similar to adults. Methods Traumatized children less than 18 years of age with an Injury Severity Score >9 points and consecutive admission to the hospital’s pediatric intensive care unit were included. Organ function was evaluated according to the score by Marshall et al. while IL-6 levels were measured repetitively every morning. Results 59 traumatized children were included (8.4 ± 4.4 years; 57.6% male gender). Incidence of MODS was 11.9%. No differences were found referring to age, gender, injury distribution or overall injury severity between children with and without MODS. Increased IL-6 levels during hospital admission were associated with injury severity (Spearman correlation: r = 0.522, p MODS was proven at that time point (Spearman correlation: r = 0.180, p = 0.231; Pearson's correlation: r = 0.297, p = 0.045). However, increased IL-6 levels during the first two days were no longer associated with the injury severity but a significant correlation to MODS was measured. Conclusions The presented prospective study is the first providing evidence for a correlation of IL-6 levels with injury severity and the incidence of MODS in traumatized children. PMID:24589345

  17. The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages.

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    Maria Ruweka Fernando

    Full Text Available Macrophages are important innate immune cells that are associated with two distinct phenotypes: a pro-inflammatory (or classically activated subset with prototypic macrophage functions such as inflammatory cytokine production and bactericidal activity, and an anti-inflammatory (or alternatively activated (AAM subset linked with wound healing and tissue repair processes. In this study, we examined the effect of interlukein-6 on human and murine macrophage polarization. The results indicate that despite being commonly associated with pro-inflammatory functions and being implicated in the pathogenesis/pathophysiology of numerous inflammatory diseases, interleukin-6 can enhance the polarization of AAMs, based on increased expression of hallmark markers: arginase-1, Ym1 and CD206; this effect required the AAM differentiating cytokines, IL-4 and IL-13. Co-treatment of AAMs with IL-6 resulted in spontaneous release of IL-10, suppressed LPS-induced nitric oxide production and inhibited cytokine production by activated CD4+ T cells - immunoregulatory features not observed in the 'parent' IL-4+IL-13-induced AAM. The effect of IL-6 required signal transducer and activator of transcription (STAT-3, was partially dependent on up-regulation of the IL4Rα chain, and was independent of autocrine IL-10. In the presence of IFNγ, IL-6 promoted the production of IL-1β and TNFα suggesting that this cytokine can enhance the phenotype to which a macrophage has committed. This finding may explain the pleiotrophic nature of IL-6, where it is associated with the perpetuation and enhancement of disease in inflammatory situations, but is also necessary for resolution of inflammation and adequate wound healing to occur in others. Thus, the potential benefit of IL-6 in promoting an AAM, with its' anti-inflammatory and wound healing ability, may need to be considered in immunotherapies aimed at in vivo modulation or inhibition of IL-6.

  18. The pro-inflammatory cytokine, interleukin-6, enhances the polarization of alternatively activated macrophages.

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    Fernando, Maria Ruweka; Reyes, Jose Luis; Iannuzzi, Jordan; Leung, Gabriella; McKay, Derek Mark

    2014-01-01

    Macrophages are important innate immune cells that are associated with two distinct phenotypes: a pro-inflammatory (or classically activated) subset with prototypic macrophage functions such as inflammatory cytokine production and bactericidal activity, and an anti-inflammatory (or alternatively activated (AAM)) subset linked with wound healing and tissue repair processes. In this study, we examined the effect of interlukein-6 on human and murine macrophage polarization. The results indicate that despite being commonly associated with pro-inflammatory functions and being implicated in the pathogenesis/pathophysiology of numerous inflammatory diseases, interleukin-6 can enhance the polarization of AAMs, based on increased expression of hallmark markers: arginase-1, Ym1 and CD206; this effect required the AAM differentiating cytokines, IL-4 and IL-13. Co-treatment of AAMs with IL-6 resulted in spontaneous release of IL-10, suppressed LPS-induced nitric oxide production and inhibited cytokine production by activated CD4+ T cells - immunoregulatory features not observed in the 'parent' IL-4+IL-13-induced AAM. The effect of IL-6 required signal transducer and activator of transcription (STAT)-3, was partially dependent on up-regulation of the IL4Rα chain, and was independent of autocrine IL-10. In the presence of IFNγ, IL-6 promoted the production of IL-1β and TNFα suggesting that this cytokine can enhance the phenotype to which a macrophage has committed. This finding may explain the pleiotrophic nature of IL-6, where it is associated with the perpetuation and enhancement of disease in inflammatory situations, but is also necessary for resolution of inflammation and adequate wound healing to occur in others. Thus, the potential benefit of IL-6 in promoting an AAM, with its' anti-inflammatory and wound healing ability, may need to be considered in immunotherapies aimed at in vivo modulation or inhibition of IL-6.

  19. Serum interleukin-6 in the diagnosis of bacterial infection in cirrhotic patients

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    Wu, Yinlian; Wang, Mingfang; Zhu, Yueyong; Lin, Su

    2016-01-01

    Abstract Background: The diagnostic accuracy of interleukin-6 (IL-6) in predicting bacterial infection in cirrhotic patients remains unclear. The aim of this meta-analysis is to explore the potential diagnostic value of IL-6 in cirrhotic patients. Methods: We systematically searched PubMed, Embase (via OvidSP), Web of Science, the Cochrane Library, and Scopus for studies published from inception to October 2015. Studies were enrolled if they included assessment of the accuracy of IL-6 in the diagnosis of bacterial infection in cirrhotic patients and provided sufficient data to construct a 2 × 2 contingency table. Results: Totally, 535 studies were searched in the initial database and finally 6 studies involving 741 patients were included for the final analysis. The pooled sensitivity, specificity and diagnostic odds ratio were 0.85 (95% confidence interval [CI], 0.64–0.94), 0.91 (95% CI, 0.80–0.96) and 52.89 (95% CI, 15.21–183.86), respectively. The pooled positive likelihood ratio was 8.99 (95% CI, 4.13–19.55) and the pooled negative likelihood ratio was 0.17 (95% CI, 0.07–0.43). The area under the receiver operating characteristic curve was 0.94 (95% CI, 0.92–0.96). Conclusion: This meta-analysis suggests IL-6 has a high diagnostic value for the differentiation of bacterial infection in patients with cirrhosis. PMID:27741137

  20. Impaired hepatic removal of interleukin-6 in patients with liver cirrhosis.

    Science.gov (United States)

    Wiest, Reiner; Weigert, Johanna; Wanninger, Josef; Neumeier, Markus; Bauer, Sabrina; Schmidhofer, Sandra; Farkas, Stefan; Scherer, Marcus N; Schäffler, Andreas; Schölmerich, Jürgen; Buechler, Christa

    2011-02-01

    Systemic concentrations of interleukin-6 (IL-6) are elevated in patients with liver cirrhosis, and impaired hepatic uptake of IL-6 was suggested to contribute to higher levels in these patients. To test this hypothesis IL-6 was measured in portal venous serum (PVS), hepatic venous serum (HVS) and systemic venous serum (SVS) of 41 patients with liver cirrhosis and four patients with normal liver function. IL-6 was higher in PVS than HVS of all blood donors and about 43% of portal vein derived IL-6 was extracted by the healthy liver, and 6.3% by the cirrhotic liver demonstrating markedly impaired removal of IL-6 by the latter. Whereas in patients with CHILD-PUGH stage A IL-6 in HVS was almost 25% lower than in PVS, in patients with CHILD-PUGH stage C IL-6 was similarly abundant in the two blood compartments. Ascites is a common complication in cirrhotic patients and was associated with higher IL-6 levels in all blood compartments without significant differences in hepatic excretion. Hepatic venous pressure gradient did not correlate with the degree of hepatic IL-6 removal excluding hepatic shunting as the principal cause of impaired IL-6 uptake. Furthermore, patients with alcoholic liver cirrhosis had higher IL-6 in all blood compartments than patients with cryptogenic liver cirrhosis. Aetiology of liver cirrhosis did not affect hepatic removal rate indicating higher IL-6 synthesis in patients with alcoholic liver cirrhosis. In summary, the current data provide evidence that impaired hepatic removal of IL-6 is explained by hepatic shunting and liver dysfunction in patients with liver cirrhosis partly explaining higher systemic levels.

  1. Interleukin-6-related genotypes, body mass index, and risk of multiple myeloma and plasmacytoma.

    Science.gov (United States)

    Cozen, Wendy; Gebregziabher, Mulugeta; Conti, David V; Van Den Berg, David J; Coetzee, Gerhard A; Wang, Sophia S; Rothman, Nathaniel; Bernstein, Leslie; Hartge, Patricia; Morhbacher, Ann; Coetzee, Simon G; Salam, Muhammad T; Wang, Wei; Zadnick, John; Ingles, Sue A

    2006-11-01

    Interleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. We evaluated IL-6 genotypes and body mass index (BMI) in a case-control study of multiple myeloma and plasmacytoma. DNA samples and questionnaires were obtained from incident cases of multiple myeloma (n = 134) and plasmacytoma (n = 16; plasma cell neoplasms) ascertained from the Los Angeles County population-based cancer registry and from siblings or cousins of cases (family controls, n = 112) and population controls (n = 126). Genotypes evaluated included IL-6 promoter gene single nucleotide polymorphisms (SNP) at positions -174, -572, and -597; one variable number of tandem repeats (-373 A(n)T(n)); and one SNP in the IL-6 receptor (IL-6ralpha) gene at position -358. The variant allele of the IL-6 promoter SNP -572 was associated with a roughly 2-fold increased risk of plasma cell neoplasms when cases were compared with family [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 0.7-4.7] or population controls (OR, 2.4; 95% CI, 1.2-4.7). The -373 9A/9A genotype was associated with a decreased risk compared with the most common genotype (OR for cases versus family controls, 0.4; 95% CI, 0.1-1.7; OR for cases versus population controls, 0.3; 95% CI, 0.1-0.9). No other SNPs were associated with risk. Obesity (BMI >or= 30 kg/m(2)) increased risk nonsignificantly by 40% and 80% when cases were compared with family controls or population controls, respectively, relative to persons with a BMI of <25 kg/m(2). These results suggest that IL-6 promoter genotypes may be associated with increased risk of plasma cell neoplasms.

  2. Interleukin-6 (-174G>C promoter polymorphism in patients infected by hepatitis B virus

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    Seref Demirbas

    2012-04-01

    Full Text Available Objective: Hepatitis B virus (HBV infection is one of the most important health problems in the world. Interleukin-6 (IL-6 has been shown to be a major inflammatory cytokine, inducing cell proliferation and expression of acute response genes, such as fibrinogen and C-reactive protein in hepatocytes. IL-6 levels are elevated in patients acutely infected with HBV and have been associated with progression of infection to chronic hepatitis. Methods: In the present study, the role of IL-6 (-174G/C polymorphism was investigated on individuals which are diagnosed as hepatitis B virus carrier (n=19, chronic hepatitis (n=10 and cirrhosis (n=13, and non-infected individuals with HBV (n=8. In order to determine IL-6 polymorphism, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method was applied using genomic DNA extracted from paraffin embedded liver needle biopsy specimens. Results: The genotype frequencies in 50 samples were observed as follows: 76% homozygote typical (GG, 22% heterozygote (GC and 2% homozygote atypical (CC. In this study, limited statistical association was observed between IL-6 polymorphism (GG, GC and CC genotype and chronic hepatitis/cirrhosis compared to hepatitis B virus carriers and non-infected individuals with HBV (p=0.045. Conclusion: As observed in only one patient with chronic hepatitis, IL-6 (-174C/C genotype is very rare in this study group. Because of lower frequency of -174C/C phenotype, studies in larger series can give statistically more precise conclusions. [J Exp Integr Med 2012; 2(2.000: 173-177

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

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    Mahmoud Imani

    2011-07-01

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

  4. Disrupted Ultradian Activity Rhythms and Differential Expression of Several Clock Genes in Interleukin-6-Deficient Mice

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    Monje, Francisco J.; Cicvaric, Ana; Acevedo Aguilar, Juan Pablo; Elbau, Immanuel; Horvath, Orsolya; Diao, Weifei; Glat, Micaela; Pollak, Daniela D.

    2017-01-01

    The characteristics of the cycles of activity and rest stand out among the most intensively investigated aspects of circadian rhythmicity in humans and experimental animals. Alterations in the circadian patterns of activity and rest are strongly linked to cognitive and emotional dysfunctions in severe mental illnesses such as Alzheimer’s disease (AD) and major depression (MDD). The proinflammatory cytokine interleukin 6 (IL-6) has been prominently associated with the pathogenesis of AD and MDD. However, the potential involvement of IL-6 in the modulation of the diurnal rhythms of activity and rest has not been investigated. Here, we set out to study the role of IL-6 in circadian rhythmicity through the characterization of patterns of behavioral locomotor activity in IL-6 knockout (IL-6 KO) mice and wild-type littermate controls. Deletion of IL-6 did not alter the length of the circadian period or the amount of locomotor activity under either light-entrained or free-running conditions. IL-6 KO mice also presented a normal phase shift in response to light exposure at night. However, the temporal architecture of the behavioral rhythmicity throughout the day, as characterized by the quantity of ultradian activity bouts, was significantly impaired under light-entrained and free-running conditions in IL-6 KO. Moreover, the assessment of clock gene expression in the hippocampus, a brain region involved in AD and depression, revealed altered levels of cry1, dec2, and rev-erb-beta in IL-6 KO mice. These data propose that IL-6 participates in the regulation of ultradian activity/rest rhythmicity and clock gene expression in the mammalian brain. Furthermore, we propose IL-6-dependent circadian misalignment as a common pathogenetic principle in some neurodegenerative and neuropsychiatric disorders.

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

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    Sheila Ranganath

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

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

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    Izziki Mohamed

    2009-01-01

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

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

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

    2012-01-15

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

  8. Transcription Factor Tfe3 Directly Regulates Pgc-1alpha in Muscle.

    Science.gov (United States)

    Salma, Nunciada; Song, Jun S; Arany, Zoltan; Fisher, David E

    2015-10-01

    The microphthalmia (MiT) family of transcription factors is an important mediator of metabolism. Family members Mitf and Tfeb directly regulate the expression of the master regulator of metabolism, peroxisome-proliferator activated receptor gamma coactivator-1 alpha (Pgc-1alpha), in melanomas and in the liver, respectively. Pgc-1alpha is enriched in tissues with high oxidative capacity and plays an important role in the regulation of mitochondrial biogenesis and cellular metabolism. In skeletal muscle, Pgc-1alpha affects many aspects of muscle functionally such as endurance, fiber-type switching, and insulin sensitivity. Tfe3 also regulates muscle metabolic genes that enhance insulin sensitivity in skeletal muscle. Tfe3 has not yet been shown to regulate Pgc-1alpha expression. Our results reported here show that Tfe3 directly regulates Pgc-1alpha expression in myotubes. Tfe3 ectopic expression induces Pgc-1alpha, and Tfe3 silencing suppresses Pgc-1alpha expression. This regulation is direct, as shown by Tfe3's binding to E-boxes on the Pgc-1alpha proximal promoter. We conclude that Tfe3 is a critical transcription factor that regulates Pgc-1alpha gene expression in myotubes. Since Pgc-1alpha coactivates numerous biological programs in diverse tissues, the regulation of its expression by upstream transcription factors such Tfe3 implies potential opportunities for the treatment of diseases where modulation of Pgc-1alpha expression may have important clinical outcomes.

  9. Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

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    Bahia, Malkeet S; Silakari, Om

    2010-05-01

    Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

  10. Role of G{alpha}12 and G{alpha}13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

    OpenAIRE

    2007-01-01

    G{alpha}12 and G{alpha}13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by G{alpha}12 and G{alpha}13. A deficiency of G{alpha}12, but not of G{alpha}13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, G{alpha}12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin a...

  11. Identification of high responders for interleukin-6 and creatine kinase following acute eccentric resistance exercise in elderly obese women.

    Science.gov (United States)

    Tajra, Vitor; Tibana, Ramires Alsamir; Vieira, Denis Cesar Leite; de Farias, Darlan Lopes; Teixeira, Tatiane Gomes; Funghetto, Silvana Schwerz; Silva, Alessandro Oliveira; de Sousa, Nuno Manuel Frade; Willardson, Jeffrey; Karnikowski, Margô Gomes Oliveira; Prestes, Jonato

    2014-11-01

    Resistance exercise is used as a non-pharmacological tool to elicit both gains in and maintenance of physical function in the elderly. Thus, the present study examined the acute response of creatine kinase and interleukin-6 following an eccentric resistance exercise session in elderly obese women classified as high responders or normal responders. Cross-sectional field study. Ninety elderly obese women (69.4 ± 6.01 years) were tested for a 10 repetition maximum on the leg extension exercise and then completed an acute eccentric resistance exercise session consisting of seven sets of 10 repetitions at 110% of 10 repetition maximum with a rest of 3 min between sets. Subjects were divided into normal response or high response on the basis of the peak serum interleukin-6 (NR = 59 and HR = 7) and creatine kinase (NR = 81 and HR = 9) concentration being greater than (HR) or less than (NR) the 90th percentile. Creatine kinase was higher at 0 h, 3h, 24h and 48 h following the ERE for the HR group. The peak creatine kinase was significantly higher in HR group versus the normal response group. The average increase in the serum interleukin-6 Δ for the HR group (∼ 850%) was significantly higher versus the normal response group (∼ 55%). Serum interleukin-6 was significantly higher at 0 h and 24h following eccentric resistance exercise only for the high response group, while peak levels were significantly higher in high response group versus the normal response group (p ≤ 0.005). Only one subject met the criteria to be classified as high response for both creatine kinase and interleukin-6 responsiveness. Elderly individuals classified as high response experienced greater creatine kinase and interleukin-6 responses to ERE. Thus, a prudent approach for eccentric resistance exercise prescription might be programming additional recovery days and/or lower intensity training, especially in the beginning stages of a program. Copyright © 2013 Sports Medicine Australia

  12. Nicotine suppresses lipopolysaccharide-induced release of interleukin-6 in mixed glia and microglia-enriched cultures

    Institute of Scientific and Technical Information of China (English)

    Zhihua Li; Qingzan Zhao; Hua Zhang; Xiuhua Ren; Mingfu Zhou; Weidong Zang

    2011-01-01

    Inflammation plays an important role in the pathogenesis of Parkinson's disease (PD) through the over-activation of microglia.Epidemiological studies show that smoking is associated with a lower incidence of PD.This study hypothesized that the neuroprotective effect of nicotine is mediated by modulating the activation of microglia via cytokine release.This study found that nicotine pretreatment suppressed the lipopolysaccharide-induced inflammatory reaction in the nervous system, especially microglia activation and interleukin-6 production.The inhibitory effects of 100 pmol/L nicotine were stronger compared with 1 and 10 pmol/L nicotine.These findings indicate that nicotine significantly decreases the production of proinflammatory interleukin-6 in mixed glia or microglia-enriched cultures, and plays an inhibitory effect on the lipopolysaccharide-induced inflammatory reaction.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-01

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

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

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    Fabjani Gerhild

    2008-01-01

    Full Text Available Abstract Background Many cancer cells produce interleukin-6 (IL-6, a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of IL-6 modulators, i.e. IL-1β, prostaglandin E2, 17β-estradiol, and 1,25-dihydroxyvitamin D3, on expression and synthesis of the cytokine at different stages of tumour progression. Methods We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the IL-6 gene promoter. Results IL-6 mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10-7 M reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the IL-6 promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the IL-6 gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-myc proto-oncogene expression. These effects were inhibited by 10-8 M 1,25-dihydroxyvitamin D3. Conclusion In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  17. Effect of Blocking with Minicircle DNA of Interleukin-6 on Skin Allograft Rejection

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    Doh Kyoung Chan

    2014-06-01

    Full Text Available Blocking of proinflammatory cytokine, interleukin-6 (IL-6 is effective in decreasing resistance to allogenic tolerance. In this study, we investigated whether anti-IL-6 receptor producing nonviral minicircle (MC-DNA, is competent to inhibit alloresponse-induced IL-6 in highly immunogenic murine skin allograft model. We designed MC-DNA producing IL-6R antibody and verified in vitro system. One day before skin allograft modeling, systemic MC-DNA exposed via hydrodynamic delivery of MC-DNA in vivo (50 ug of DNA, tail vein, single injection. Using GFP tagging MC-DNA, we confirmed its organ distribution. At day 5, we measured the amount of IL-6 and IL-6R antibody in serum. As functional examinations, we evaluated survival rate, morphological changes of graft, immune cell infiltration, and population of T helper 17 cells (Th17, FACS marker: CD4+/RoRγt and regulatory T cells (Treg, FACS marker: CD4+ Foxp3+. We compared its alloimmunity and graft survival efficiency with the cyclosporine A (CsA-treated group (50 mg/kg, daily administration via oral gavage. Hydrodynamic delivery of MC-DNA was mainly localized in hepatocytes. Serum IL-6 and IL-6R antibody detected in anti-IL-6R MC-DNA treated mice. At day 8.5, untreated mice completely rejected the graft confirming by daily observation of loss of skin graft and erosion. However, mice received either anti-IL-6R MC-DNA or CsA presented prolonged acceptance of graft until day 15 or 15.6, respectively. Results from morphological changes and immune cell infiltration in the graft were also consistent with survival rate. FACS results showed that anti-IL-6R MC-DNA treatment markedly suppressed Th17 population compared with the untreated mice. However, there was no effect on Treg population. On the other hand, administration of CsA showed the increased Th17 and decreased Treg population compared with untreated group. We found that single injection of nonviral minicircle DNA targeting IL-6R is effective in both

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

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    Davood Attaran

    2010-09-01

    disease, interleukin-6, inflammation, chemical warfare

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

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    Jeffrey K Lee

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

  20. INTERLEUKIN-6 PROTECTS ANNULUS FIBROSUS CELL FROM APOPTOSIS INDUCED BY INTERLEUKIN-1 IN VITRO

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the effect of interleukin-6 (IL-6) on the apoptosis of annulus fibrosus (AF) cell induced by interleukin-1 β (IL-1 β).Methods Cultured AF cells were divided into 6 groups and treated with no drug, 10 ng/mL IL-6, 10 ng/mL IL1β, 10 ng/mL IL-1β and Z-VAD-FMK (a caspase-9 inhibitor), 10 ng/mL IL-1β and 10 ng/mL IL-6, 10 ng/mL IL-1β and 100 ng/mL IL-6, respectively. After three days of culture, the apoptosis rate, the positive rates of caspase3, -8, and -9 of AF cells were detected with flow cytometry.Results The apoptosis rates of cells in group 1 to 6 were 2. 67%±1.08%, 2.71%±0.53%, 20.37%±1.57%, 11.34%±0.67%, 18.17%±0.74%, and 9.42%±1.08%, respectively. There was no significant difference between group 1 and 2, while the apoptosis rates of group 4, 5, and 6 were significantly lower than group 3 (P=0.001, P=0.172, and P=0.001, respectively). Positive rates of caspase-3 in group 5 (12.35%± 0.64%) and 6(9.26%±0.36%) were significantly lower than group 3 (17.14%±0.72%; P=0.001 and P<0.001, respectively). And positive rates of caspase-9 in group 5 (15.13%±1.45%) and 6 (10.17%±2.50%) were significantly lower than group 3 (19.4%±0.98%;P=0.014 and P=0.004, respectively). But there was not obvious change of caspase-8 activity after IL-6 was added.Conclusion IL-6 is capable of protecting AF cells from IL-1 β induced apoptosis in vitro. Mechanism of the protection is related with the inhibition of caspase-3 and -9 activities.

  1. Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Soresi Maurizio; Giannitrapani Lydia; D'Antona Fabio; Florena Ada Maria; La Spada Emanuele; Terranova Angela; Cervello Melchiorre; D'Alessandro Natale; Montalto Giuseppe

    2006-01-01

    AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group.METHODS: Three groups of subjects were studied:group Ⅰ (n=83) suffering from HCC and LC, group Ⅱ (n=72) suffering from LC alone and group Ⅲ (n =42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R.RESULTS: Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups (P< 0.0001). There was no significant difference in sIL-6R concentrations among 3 groups.When the patients with HCC were divided into groups according to Okuda's classification, a significant serum increase of IL-6 and sIL-6R level was observed from stage Ⅰ to stage Ⅲ (P<0.02, P<0.0005). When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class (P< 0.01).CONCLUSION: IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells. sIL-6R values are similar in all groups, increasing only in stage Ⅲ HCC patients. These data suggest that they have a closer

  2. Novel single nucleotide polymorphisms in interleukin 6 affect tacrolimus metabolism in liver transplant patients.

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    Dawei Chen

    Full Text Available BACKGROUND: Tacrolimus is the first-line immunosuppressant after organ transplantation. It is mainly metabolized by cytochrome P450, family 3, subfamily A (CYP3A enzymes, but there are large individual differences in metabolism. Interleukin 6 (IL6 has been shown to cause a pan-suppression of mRNA levels of ten major CYP enzymes in human hepatocyte cultures. IL6 has been shown to provide hepatoprotection in various models of liver injury. Rs1800796 is a locus in the IL6 gene promoter region which regulates cytokine production. We speculated that IL6 rs1800796 polymorphisms may lead to individual differences in tacrolimus metabolism by affecting CYP3A enzymes levels and liver function after liver transplantation. METHODOLOGY/PRINCIPAL FINDINGS: Ninety-six liver transplant patients receiving tacrolimus were enrolled in the study. Two single nucleotide polymorphisms (SNP, CYP3A5 rs776746 and IL6 rs1800796, were genotyped in both donors and recipients. The effects of SNPs on tacrolimus concentration/dose (C/D ratio at four weeks after transplantation were studied, as well as the effects of donor IL6 rs1800796 polymorphisms on liver function. Both donor and recipient CYP3A5 rs776746 allele A showed association with lower C/D ratios, while donor IL6 rs1800796 allele G showed an association with higher C/D ratios. Donor CYP3A5 rs776746 allele A, IL6 rs1800796 allele C, and recipient CYP3A5 rs776746 allele A were associated with fast tacrolimus metabolism. With increasing numbers of these alleles, patients were found to have increasingly lower tacrolimus C/D ratios at time points after transplantation. Donor IL6 rs1800796 allele G carriers showed an association with higher glutamic-pyruvic transaminase (GPT levels. CONCLUSIONS: Combined analysis of donor CYP3A5 rs776746, IL6 rs1800796, and recipient CYP3A5 rs776746 polymorphisms may distinguish tacrolimus metabolism better than CYP3A5 rs776746 alone. IL6 may lead to individual differences in tacrolimus

  3. Heteroarylketones inhibit astroglial interleukin-6 expression via a STAT3/NF-κB signaling pathway

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    Kehlen Astrid

    2011-07-01

    Full Text Available Abstract Background Elevated brain levels of the pleiotropic cytokine interleukin-6, which is mainly secreted from activated local astrocytes, contribute to pathological events including neuroinflammation and neurodegeneration. Thus, inhibition of pathological IL-6 expression provides a rationale strategy for targeting the onset or further progression of neurological disorders including Alzheimer's disease, multiple sclerosis, Parkinson's disease and traumatic brain injury. The purpose of this study was to identify and to characterize new potent inhibitors of astrocytic IL-6 expression for further therapeutic development of novel anti-inflammatory and neuroprotective drugs. Methods Oncostatin M (OSM-treated human glioma U343 cells were used as model for induction of astrocytic IL-6 expression. This model was characterized by immunoblotting, siRNA technique, ELISA and qRT-PCR and used to screen low molecular weight compound libraries for IL-6-lowering effects. To validate bioactive compounds identified from library screens, bacterial lipopolysaccharide was used to induce IL-6 expression in cultivated primary astrocytes and in mice in vivo. To dissect underlying molecular mechanisms, protein extracts from OSM-treated U343 cells were analyzed by phospho-specific immunoblotting and immunocytochemistry as well as by co-immunoprecipitation. Results OSM-treatment (100 ng/ml; 24 h led to 30-fold increase of IL-6 secretion from U343 cells. The temporal profile of IL-6 mRNA induction displayed a biphasic induction pattern with peak synthesis at 1 h (6.5-fold and 16 h (5.5-fold post stimulation. IL-6 protein release did not show that biphasic pattern and was detected as early as 3 h post stimulation reaching a maximum at 24 h. The screen of compound libraries identified a set of heteroarylketones (HAKs as potent inhibitors of IL-6 secretion. HAK compounds affected the second peak in IL-6 mRNA synthesis, whereas the first peak was insensitive to HAK

  4. Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity

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    Gabriel Olmos

    2014-01-01

    Full Text Available Tumor necrosis factor alpha (TNF-α is a proinflammatory cytokine that exerts both homeostatic and pathophysiological roles in the central nervous system. In pathological conditions, microglia release large amounts of TNF-α; this de novo production of TNF-α is an important component of the so-called neuroinflammatory response that is associated with several neurological disorders. In addition, TNF-α can potentiate glutamate-mediated cytotoxicity by two complementary mechanisms: indirectly, by inhibiting glutamate transport on astrocytes, and directly, by rapidly triggering the surface expression of Ca+2 permeable-AMPA receptors and NMDA receptors, while decreasing inhibitory GABAA receptors on neurons. Thus, the net effect of TNF-α is to alter the balance of excitation and inhibition resulting in a higher synaptic excitatory/inhibitory ratio. This review summarizes the current knowledge of the cellular and molecular mechanisms by which TNF-α links the neuroinflammatory and excitotoxic processes that occur in several neurodegenerative diseases, but with a special emphasis on amyotrophic lateral sclerosis (ALS. As microglial activation and upregulation of TNF-α expression is a common feature of several CNS diseases, as well as chronic opioid exposure and neuropathic pain, modulating TNF-α signaling may represent a valuable target for intervention.

  5. Combined use of serum adiponectin and tumor necrosis factor-alpha receptor 2 levels was comparable to 2-hour post-load glucose in diabetes prediction.

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    Yu-Cho Woo

    Full Text Available BACKGROUND: Adipose tissue inflammation and dysregulated adipokine secretion are implicated in obesity-related insulin resistance and type 2 diabetes. We evaluated the use of serum adiponectin, an anti-inflammatory adipokine, and several proinflammatory adipokines, as biomarkers of diabetes risk and whether they add to traditional risk factors in diabetes prediction. METHODS: We studied 1300 non-diabetic subjects from the prospective Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS. Serum adiponectin, tumor necrosis factor-alpha receptor 2 (TNF-α R2, interleukin-6 (IL-6, adipocyte-fatty acid binding protein (A-FABP and high-sensitivity C-reactive protein (hsCRP were measured in baseline samples. RESULTS: Seventy-six participants developed diabetes over 5.3 years (median. All five biomarkers significantly improved the log-likelihood of diabetes in a clinical diabetes prediction (CDP model including age, sex, family history of diabetes, smoking, physical activity, hypertension, waist circumference, fasting glucose and dyslipidaemia. In ROC curve analysis, "adiponectin + TNF-α R2" improved the area under ROC curve (AUC of the CDP model from 0.802 to 0.830 (P = 0.03, rendering its performance comparable to the "CDP + 2-hour post-OGTT glucose" model (AUC = 0.852, P = 0.30. A biomarker risk score, derived from the number of biomarkers predictive of diabetes (low adiponectin, high TNF-α R2, had similar performance when added to the CDP model (AUC = 0.829 [95% CI: 0.808-0.849]. CONCLUSIONS: The combined use of serum adiponectin and TNF-α R2 as biomarkers provided added value over traditional risk factors for diabetes prediction in Chinese and could be considered as an alternative to the OGTT.

  6. Hubungan antara Kadar Interleukin-6 (IL-6) dengan Disease Activity Score-28 (DAS28) pada Artritis Reumatoid

    OpenAIRE

    Ariestine, Dina Aprillia

    2012-01-01

    Background and Aim: Rheumatoid arthritis is a chronic inflammation disorder which various cytokines have important roles in inflammatory process and joint destruction. One of these is interleukin-6 (IL-6), abundantly expressed in the serum and synovial fibroblasts of patients with rheumatoid arthritis and its level correlates with the disease activity and joint destruction. Disease Activity Score-28 (DAS28) has been the most commonly used to measure the disease activity. This study aimed to d...

  7. Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary disease: effect of carbocysteine lysine salt monohydrate (SCMC-Lys).

    Science.gov (United States)

    Carpagnano, Giovanna E; Resta, O; Foschino-Barbaro, Maria P; Spanevello, Antonio; Stefano, Antonio; Di Gioia, Giuseppe; Serviddio, Gaetano; Gramiccioni, Enzo

    2004-11-28

    Chronic obstructive pulmonary disease (COPD) is characterized by an airways inflammation and by an enhanced generation of reactive oxygen species. The aim of our study was to assess the inflammation and the oxidative stress in airways of COPD patients with acute exacerbation of disease and in stability. Furthermore, we investigated the anti-inflammatory and antioxidant effects of 6 months treatment with carbocysteine lysine salt monohydrate (SCMC-Lys) in COPD. We studied 30 mild acute COPD, 10 mild stable COPD and 15 healthy subjects. 8-isoprostane and Interleukine-6 were measured in their breath condensate through immunoassay. Significantly higher concentrations of exhaled 8-isoprostane and Interleukine-6 were found in acute COPD patients compared to stable COPD and healthy controls (21.8+/-5.1 vs. 13.2+/-2.0 vs. 4.7+/-1.8 pg/ml and 7.4+/-0.9 vs. 5.8+/-0.2 vs. 2.7+/-0.6 pg/ml, p<0.0001). COPD patients treated with SCMC-Lys showed a marked reduction of exhaled 8-isoprostane and Interleukine-6 (8.9+/-1.5 and 4.6+/-0.8 pg/ml, p<0.0001). These findings suggest that there is an increase of 8-isoprostane and Interleukine-6 concentrations in the breath condensate of COPD patients compared to healthy controls especially during acute exacerbations of the disease. Moreover, we showed an anti-inflammatory and antioxidant effect of short-term administration of SCMC-Lys in COPD, suggesting the importance of a further placebo-controlled study that should evaluate the effects of this drug.

  8. A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth

    DEFF Research Database (Denmark)

    Greenberger, Lee M; Horak, Ivan D; Filpula, David

    2008-01-01

    Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays a critical role in angiogenesis, survival, metastasis, drug resistance, and glucose metabolism. Elevated expression of the alpha-subunit of HIF-1 (HIF-1alpha), which occurs in response to hypoxia or activation of growth facto...

  9. Multiple post-translational modifications in hepatocyte nuclear factor 4{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Atsushi; Katsura, Shogo; Ito, Ryo; Hashiba, Waka; Sekine, Hiroki; Fujiki, Ryoji [Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Kato, Shigeaki, E-mail: uskato@mail.ecc.u-tokyo.ac.jp [Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan)

    2011-07-15

    Highlights: {yields} We performed comprehensive PTM analysis for HNF4{alpha} protein. {yields} We identified 8 PTMs in HNF4{alpha} protein including newly identified PTMs. {yields} Among them, we found acetylation at lysine 458 was one of the prime PTMs for HNF4{alpha} function. {yields} Acetylation at lysine 458 was inhibitory for HNF4{alpha} transcription function. {yields} This modification fluctuated in response to extracellular condition. -- Abstract: To investigate the role of post-translational modifications (PTMs) in the hepatocyte nuclear factor 4{alpha} (HNF4{alpha})-mediated transcription, we took a comprehensive survey of PTMs in HNF4{alpha} protein by massspectrometry and identified totally 8 PTM sites including newly identified ubiquitilation and acetylation sites. To assess the impact of identified PTMs in HNF4{alpha}-function, we introduced point mutations at the identified PTM sites and, tested transcriptional activity of the HNF4{alpha}. Among the point-mutations, an acetylation site at lysine 458 was found significant in the HNF4{alpha}-mediated transcriptional control. An acetylation negative mutant at lysine 458 showed an increased transcriptional activity by about 2-fold, while an acetylation mimic mutant had a lowered transcriptional activation. Furthermore, this acetylation appeared to be fluctuated in response to extracellular nutrient conditions. Thus, by applying an comprehensive analysis of PTMs, multiple PTMs were newly identified in HNF4{alpha} and unexpected role of an HNF4{alpha} acetylation could be uncovered.

  10. HIV-1 gp120 activates the STAT3/interleukin-6 axis in primary human monocyte-derived dendritic cells.

    Science.gov (United States)

    Del Cornò, Manuela; Donninelli, Gloria; Varano, Barbara; Da Sacco, Letizia; Masotti, Andrea; Gessani, Sandra

    2014-10-01

    Dendritic cells (DCs) are fundamental for the initiation of immune responses and are important players in AIDS immunopathogenesis. The modulation of DC functional activities represents a strategic mechanism for HIV-1 to evade immune surveillance. Impairment of DC function may result from bystander effects of HIV-1 envelope proteins independently of direct HIV-1 infection. In this study, we report that exposure of immature monocyte-derived DCs (MDDCs) to HIV-1 R5 gp120 resulted in the CCR5-dependent production of interleukin-6 (IL-6) via mitogen-activated protein kinase (MAPK)/NF-κB pathways. IL-6 in turn activated STAT3 by an autocrine loop. Concomitantly, gp120 promoted an early activation of STAT3 that further contributed to IL-6 induction. This activation paralleled a concomitant upregulation of the STAT3 inhibitor PIAS3. Notably, STAT3/IL-6 pathway activation was not affected by the CCR5-specific ligand CCL4. These results identify STAT3 as a key signaling intermediate activated by gp120 in MDDCs and highlight the existence of a virus-induced dysregulation of the IL-6/STAT3 axis. HIV-1 gp120 signaling through STAT3 may provide an explanation for the impairment of DC function observed upon HIV exposure. This study provides new evidence for the molecular mechanisms and signaling pathways triggered by HIV-1 gp120 in human DCs in the absence of productive infection, emphasizing a role of aberrant signaling in early virus-host interaction, contributing to viral pathogenesis. We identified STAT3 as a key component in the gp120-mediated signaling cascade involving MAPK and NF-κB components and ultimately leading to IL-6 secretion. STAT3 now is recognized as a key regulator of DC functions. Thus, the identification of this transcription factor as a signaling molecule mediating some of gp120's biological effects unveils a new mechanism by which HIV-1 may deregulate DC functions and contribute to AIDS pathogenesis. Copyright © 2014, American Society for Microbiology

  11. Replication and meta-analysis of the gene-environment interaction between body mass index and the interleukin-6 promoter polymorphism with higher insulin resistance.

    Science.gov (United States)

    Underwood, Patricia C; Chamarthi, Bindu; Williams, Jonathan S; Sun, Bei; Vaidya, Anand; Raby, Benjamin A; Lasky-Su, Jessica; Hopkins, Paul N; Adler, Gail K; Williams, Gordon H

    2012-05-01

    Insulin resistance (IR) is a complex disorder caused by an interplay of both genetic and environmental factors. Recent studies identified a significant interaction between body mass index (BMI) and the rs1800795 polymorphism of the interleukin-6 gene that influences both IR and onset of type 2 diabetes mellitus, with obese individuals homozygous for the C allele demonstrating the highest level of IR and greatest risk for type 2 diabetes mellitus. Replication of a gene-environment interaction is important to confirm the validity of the initial finding and extend the generalizability of the results to other populations. Thus, the objective of this study was to replicate this gene-environment interaction on IR in a hypertensive population and perform a meta-analysis with prior published results. The replication analysis was performed using white individuals with hypertension from the Hypertensive Pathotype cohort (N = 311), genotyped for rs1800795. Phenotype studies were conducted after participants consumed 2 diets--high sodium (200 mmol/d) and low sodium (10 mmol/d)--for 7 days each. Measurements for plasma glucose, insulin, and interleukin-6 were obtained after 8 hours of fasting. Insulin resistance was characterized by the homeostatic model assessment (HOMA-IR). In Hypertensive Pathotype, BMI was a significant effect modifier of the relationship between rs1800795 and HOMA-IR; higher BMI was associated with higher HOMA-IR among homozygote CC individuals when compared with major allele G carriers (P = .003). Furthermore, the meta-analysis in 1028 individuals confirmed the result, demonstrating the same significant interaction between rs1800795 and BMI on HOMA-IR (P = 1.05 × 10(-6)). This rare replication of a gene-environment interaction extends the generalizability of the results to hypertension while highlighting this polymorphism as a marker of IR in obese individuals.

  12. Host genetic variants in the interleukin-6 promoter predict poor outcome in patients with estrogen receptor-positive, node-positive breast cancer.

    Science.gov (United States)

    DeMichele, Angela; Gray, Robert; Horn, Michelle; Chen, Jinbo; Aplenc, Richard; Vaughan, William P; Tallman, Martin S

    2009-05-15

    Interleukin-6 modulates immune response, estrogen production, and growth pathways in breast cancer. We evaluated the effect of several common, functional interleukin-6 promoter variants in node-positive breast cancer patients enrolled on a multicenter, cooperative group, adjuvant chemotherapy trial to determine whether these variants were associated with clinical outcome overall and by estrogen receptor tumor phenotype. Genomic DNA and clinical data were collected from a clinical trial of adjuvant anthracycline-based chemotherapy followed by randomization to high-dose cyclophosphamide/thiotepa or observation (Intergroup Trial 0121). Genotyping for -174G>C (rs1800795), -597G>A (rs1800797), and -572G>C (rs1800796) was done by site-specific PCR and PyroSequencing, whereas the -373A(n)T(n) repeat was directly sequenced. Log-rank tests and Cox modeling were used to compare outcomes by genotype/haplotype and other factors. Three hundred forty-six patients (64% of trial) had corresponding genotype/clinical data available and did not differ from overall trial participants. After adjustment, patients with estrogen receptor-positive tumors and genotypes 597 GG or 174 GG had significantly worse disease-free survival [hazard ratio (HR), 1.6; P = 0.02 and HR, 1.71; P = 0.007, respectively], whereas the 373 8A12T repeat appeared to be protective (HR, 0.62; P = 0.02). The presence of at least one copy of the haplotype ([-597G, -572G, -373[10A/11T], -174G]) was associated with worse disease-free survival (HR, 1.46; P = 0.04). Kaplan-Meier plots show that all patients in this group relapsed by 24 months from diagnosis. This poor-risk haplotype was quite common overall (estimated frequency, 0.20) and twice as frequent among Blacks (estimated frequency, 0.41).

  13. Tumor Necrosis Factor alpha (TNF{alpha}) regulates CD40 expression through SMAR1 phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Kamini; Sinha, Surajit; Malonia, Sunil Kumar; Chattopadhyay, Samit, E-mail: samit@nccs.res.in

    2010-01-08

    CD40 plays an important role in mediating inflammatory response and is mainly induced by JAK/STAT phosphorylation cascade. TNF{alpha} is the key cytokine that activates CD40 during inflammation and tumorigenesis. We have earlier shown that SMAR1 can repress the transcription of Cyclin D1 promoter by forming a HDAC1 dependent repressor complex. In this study, we show that SMAR1 regulates the transcription of NF-{kappa}B target gene CD40. SMAR1 recruits HDAC1 and forms a repressor complex on CD40 promoter and keeps its basal transcription in check. Further, we show that TNF{alpha} stimulation induces SMAR1 phosphorylation at Ser-347 and promotes its cytoplasmic translocation, thus releasing its negative effect. Concomitantly, TNF{alpha} induced phosphorylation of STAT1 at Tyr-701 by JAK1 facilitates its nuclear translocation and activation of CD40 through p300 recruitment and core Histone-3 acetylation. Thus, TNF{alpha} mediated regulation of CD40 expression occurs by dual phosphorylation of SMAR1 and STAT1.

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

    Directory of Open Access Journals (Sweden)

    Wei Xia

    2015-01-01

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

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

    Science.gov (United States)

    Xia, Wei; Peng, Guo-Yi; Sheng, Jiang-Tao; Zhu, Fang-Fang; Guo, Jing-Fang; Chen, Wei-Qiang

    2015-04-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Wei Xia; Guo-yi Peng; Jiang-tao Sheng; Fang-fang Zhu; Jing-fang Guo; Wei-qiang Chen

    2015-01-01

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

  17. Sesamin modulates tyrosine hydroxylase, superoxide dismutase, catalase, inducible NO synthase and interleukin-6 expression in dopaminergic cells under MPP+-induced oxidative stress.

    Science.gov (United States)

    Lahaie-Collins, Vicky; Bournival, Julie; Plouffe, Marilyn; Carange, Julie; Martinoli, Maria-Grazia

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Vicky Lahaie-Collins

    2008-01-01

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

  19. Transcription factors interacting with herpes simplex virus alpha gene promoters in sensory neurons.

    Science.gov (United States)

    Hagmann, M; Georgiev, O; Schaffner, W; Douville, P

    1995-01-01

    Interference with VP16-mediated activation of herpes virus immediate-early (or alpha) genes is thought to be the major cause of establishing viral latency in sensory neurons. This could be brought about by lack of a key activating transcription factor(s) or active repression. In this study we find that sensory neurons express all important components for VP16-mediated alpha gene induction, such as the POU transcription factor Oct-1, host cell factor (HCF) and GABP alpha/beta. However, Oct-1 and GABP alpha/beta are only present at low levels and the VP16-induced complex (VIC) appears different. We do not find protein expression of the transcription factor Oct-2, implicated by others as an alpha gene repressor. The POU factor N-Oct3 (Brn 2 or POU3F2) is also present in sensory neurons and binds viral TAATGARAT motifs with higher affinity than Oct-1, indicating that it may be a candidate repressor for competitive binding to TAATGARAT motifs. When transfected into HeLa cells, where Oct-1 and GABP alpha/beta are highly abundant, N-Oct3 represses model promoters with multimerized TAATGARAT motifs, but fails to repress complete alpha gene promoters. Taken together our findings suggest that modulation of alpha gene promoters could contribute to viral latency when low concentrations of the activating transcription factors Oct-1 and GABP alpha/beta prevail. Our data, however, refute the notion that competing Oct factors are able to block alpha gene transcription to achieve viral latency. Images PMID:8559654

  20. Density-dependent nerve growth factor regulation of Gs-alpha RNA in pheochromocytoma 12 cells.

    Science.gov (United States)

    Tjaden, G; Aguanno, A; Kumar, R; Benincasa, D; Gubits, R M; Yu, H; Dolan, K P

    1990-01-01

    Nerve growth factor (NGF) affects levels of the alpha subunit of the stimulatory G protein (Gs-alpha) in pheochromocytoma 12 cells in a bidirectional, density-dependent manner. Cells grown at high density responded to NGF treatment with increased levels of Gs-alpha mRNA and protein. Conversely, in cells grown in low-density cultures, levels of this mRNA were lowered by NGF treatment. Images PMID:2160599

  1. Antioxidant alpha-lipoic acid inhibits osteoclast differentiation by reducing nuclear factor-kappaB DNA binding and prevents in vivo bone resorption induced by receptor activator of nuclear factor-kappaB ligand and tumor necrosis factor-alpha.

    Science.gov (United States)

    Kim, Hyon Jong; Chang, Eun-Ju; Kim, Hyun-Man; Lee, Seung Bok; Kim, Hyun-Duck; Su Kim, Ghi; Kim, Hong-Hee

    2006-05-01

    The relationship between oxidative stress and bone mineral density or osteoporosis has recently been reported. As bone loss occurring in osteoporosis and inflammatory diseases is primarily due to increases in osteoclast number, reactive oxygen species (ROS) may be relevant to osteoclast differentiation, which requires receptor activator of nuclear factor-kappaB ligand (RANKL). Tumor necrosis factor-alpha (TNF-alpha) frequently present in inflammatory conditions has a profound synergy with RANKL in osteoclastogenesis. In this study, we investigated the effects of alpha-lipoic acid (alpha-LA), a strong antioxidant clinically used for some time, on osteoclast differentiation and bone resorption. At concentrations showing no growth inhibition, alpha-LA potently suppressed osteoclastogenesis from bone marrow-derived precursor cells driven either by a high-dose RANKL alone or by a low-dose RANKL plus TNF-alpha (RANKL/TNF-alpha). alpha-LA abolished ROS elevation by RANKL or RANKL/TNF-alpha and inhibited NF-kappaB activation in osteoclast precursor cells. Specifically, alpha-LA reduced DNA binding of NF-kappaB but did not inhibit IKK activation. Furthermore, alpha-LA greatly suppressed in vivo bone loss induced by RANKL or TNF-alpha in a calvarial remodeling model. Therefore, our data provide evidence that ROS plays an important role in osteoclast differentiation through NF-kappaB regulation and the antioxidant alpha-lipoic acid has a therapeutic potential for bone erosive diseases.

  2. The role of transforming growth factor alpha in rat craniofacial development and chondrogenesis.

    Science.gov (United States)

    Huang, L; Solursh, M; Sandra, A

    1996-08-01

    To explore the possible role of transforming growth factor alpha (TGF-alpha) in craniofacial development, its expression in the craniofacial region of rat embryos from embryonic day (d) 9 to d 20 was examined by in situ hybridisation and immunostaining. The TGF-alpha transcripts were first detected in the neural fold of embryonic d 9 and 10 embryos. In the craniofacial region, the TGF-alpha transcripts were not detected until embryonic d 16 in mesenchyme surrounding the olfactory bulb, within the olfactory bulb, the nasal capsule, vomeronasal organ, and vibrissal follicle. In addition, TGF-alpha message was detected in mesenchyme in the vicinity of Meckel's cartilage, and in the dental epithelium and lamina. This expression pattern of TGF-alpha transcripts persisted until embryonic d 17 but disappeared by d 18. The presence of TGF-alpha protein largely coincided with TGF-alpha message although, unlike the message, it persisted throughout later embryogenesis in the craniofacial region. The possible function of TGF-alpha in chondrogenesis was explored by employing the micromass culture technique. Cartilage nodule formation in mesenchymal cells cultured from rat mandibles in the presence of TGF-alpha was significantly inhibited. This inhibitory effect of TGF-alpha on chondrogenesis was reversed by addition of antibody against the EGF receptor, which crossreacts with the TGF-alpha receptor. The inhibitory effect of TGF-alpha on chondrogenesis in vitro was further confirmed by micromass culture using mesenchymal cells from rat embryonic limb bud. Taken together, these results demonstrate the involvement of TGF-alpha in chondrogenesis during embryonic development, possibly by way of a specific inhibition of cartilage formation from mesenchymal precursor cells.

  3. Estimation of the Alpha Factor Parameters Using the ICDE Database

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Dae Il; Hwang, M. J.; Han, S. H

    2007-04-15

    Detailed common cause failure (CCF) analysis generally need for the data for CCF events of other nuclear power plants because the CCF events rarely occur. KAERI has been participated at the international common cause failure data exchange (ICDE) project to get the data for the CCF events. The operation office of the ICDE project sent the CCF event data for EDG to the KAERI at December 2006. As a pilot study, we performed the detailed CCF analysis of EDGs for Yonggwang Units 3 and 4 and Ulchin Units 3 and 4 using the ICDE database. There are two onsite EDGs for each NPP. When an offsite power and the two onsite EDGs are not available, one alternate AC (AAC) diesel generator (hereafter AAC) is provided. Two onsite EDGs and the AAC are manufactured by the same company, but they are designed differently. We estimated the Alpha Factor and the CCF probability for the cases where three EDGs were assumed to be identically designed, and for those were assumed to be not identically designed. For the cases where three EDGs were assumed to be identically designed, double CCF probabilities of Yonggwang Units 3/4 and Ulchin Units 3/4 for 'fails to start' were estimated as 2.20E-4 and 2.10E-4, respectively. Triple CCF probabilities of those were estimated as 2.39E-4 and 2.42E-4, respectively. As each NPP has no experience for 'fails to run', Yonggwang Units 3/4 and Ulchin Units 3/4 have the same CCF probability. The estimated double and triple CCF probabilities for 'fails to run' are 4.21E-4 and 4.61E-4, respectively. Quantification results show that the system unavailability for the cases where the three EDGs are identical is higher than that where the three EDGs are different. The estimated system unavailability of the former case was increased by 3.4% comparing with that of the latter. As a future study, a computerization work for the estimations of the CCF parameters will be performed.

  4. Tumor necrosis factor (TNF)-alpha, soluble TNF receptors and endometrial cancer risk : the EPIC study

    NARCIS (Netherlands)

    Dossus, Laure; Becker, Susen; Rinaldi, Sabina; Lukanova, Annekatrin; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Chabbert-Buffet, Nathalie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise; Teucher, Birgit; Chang-Claude, Jenny; Pischon, Tobias; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Valanou, Elisavet; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Galasso, Rocco; Redondo, Maria-Luisa; Bonet Bonet, Catalina; Molina-Montes, Esther; Altzibar, Jone M.; Chirlaque, Maria-Dolores; Ardanaz, Eva; Bueno-de-Mesquita, H. Bas; van Duijnhoven, Franzel J. B.; Peeters, Petra H. M.; Onland-Moret, N. Charlotte; Lundin, Eva; Idahl, Annika; Khaw, Kay-Tee; Wareham, Nicholas; Allen, Naomi; Romieu, Isabelle; Fedirko, Veronika; Hainaut, Pierre; Romaguera, Dora; Norat, Teresa; Riboli, Elio; Kaaks, Rudolf

    2011-01-01

    Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-alpha (TNF-alpha), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospect

  5. Influence of some factors on alpha energy spectrum of 241Am fire alarm source

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Several primary factors influencing the alpha energy spectrum of 241Am fire alarm source have been studied in order to get betteralpha energy spectrum.The results show that the homogeneity andthe thickness of metal surface coat and the size of active area of thesource have considerable influence on the alpha energy spectrum of thesource.

  6. Consideration of Real World Factors Influencing Greenhouse Gas Emissions in ALPHA

    Science.gov (United States)

    Discuss a variety of factors that influence the simulated fuel economy and GHG emissions that are often overlooked and updates made to ALPHA based on actual benchmarking data observed across a range of vehicles and transmissions. ALPHA model calibration is also examined, focusin...

  7. Factors affecting the solubility of Bacillus halmapalus alpha-amylase

    DEFF Research Database (Denmark)

    Faber, Cornelius; Hobley, Timothy John; Mollerup, Jørgen

    2008-01-01

    A detailed study of the solubility of recombinant Bacillus halmapalus alpha-amylase has been conducted. A semi-purified preparation from a bulk crystallisation was chos en that contained six isoforms with pI-values of between 5.5 and 6.1. The solubility was strongly affected by pH and could...

  8. Tumor necrosis factor-alpha modulates human in vivo lipolysis

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Fischer, Christian P; Ibfelt, Tobias;

    2008-01-01

    in lipolysis, increasing circulatory free fatty acid (FFA) levels. SUBJECTS AND METHODS: Using a randomized controlled, crossover design, healthy young male individuals (n = 10) received recombinant human (rh) TNF-alpha (700 ng/m(-2).h(-1)) for 4 h, and energy metabolism was evaluated using a combination...

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  10. Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6.

    Directory of Open Access Journals (Sweden)

    William Whiteley

    2009-09-01

    Full Text Available BACKGROUND: The objective of this study was to determine whether: (a markers of acute inflammation (white cell count, glucose, interleukin-6, C-reactive protein, and fibrinogen are associated with poor outcome after stroke and (b the addition of markers to previously validated prognostic models improves prediction of poor outcome. METHODS AND FINDINGS: We prospectively recruited patients between 2002 and 2005. Clinicians assessed patients and drew blood for inflammatory markers. Patients were followed up by postal questionnaire for poor outcome (a score of>2 on the modified Rankin Scale and death through the General Register Office (Scotland at 6 mo. We performed a systematic review of the literature and meta-analysis of the association between interleukin-6 and poor outcome after stroke to place our study in the context of previous research. We recruited 844 patients; mortality data were available in 844 (100% and functional outcome in 750 (89%. After appropriate adjustment, the odds ratios for the association of markers and poor outcome (comparing the upper and the lower third were interleukin-6, 3.1 (95% CI: 1.9-5.0; C-reactive protein, 1.9 (95% CI: 1.2-3.1; fibrinogen, 1.5 (95% CI: 1.0-2.36; white cell count, 2.1 (95% CI: 1.3-3.4; and glucose 1.3 (95% CI: 0.8-2.1. The results for interleukin-6 were similar to other studies. However, the addition of inflammatory marker levels to validated prognostic models did not materially improve model discrimination, calibration, or reclassification for prediction of poor outcome after stroke. CONCLUSIONS: Raised levels of markers of the acute inflammatory response after stroke are associated with poor outcomes. However, the addition of these markers to a previously validated stroke prognostic model did not improve the prediction of poor outcome. Whether inflammatory markers are useful in prediction of recurrent stroke or other vascular events is a separate question, which requires further study. Please

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    was to determine the effect of Interleukin-6 (IL6) infusion on circulating adipokines and on gene expression in human adipose tissue. To do this we used real-time RT-PCR. Methods  Both diabetic and control subjects underwent basal skeletal muscle and subcutaneous adipose tissue biopsies. A subset...... (PPARGC1A), carnitine palmitoyltransferase 1B and solute carrier family 2 (facilitated glucose transporter), member 4 (formerly known as glucose transporter 4/GLUT4), was higher in adipose tissue, but lower in skeletal muscle of diabetic patients than in that of control subjects. In addition, uncoupling...

  12. Interleukin-6 gene knockout influences energy balance regulating peptides in the hypothalamic paraventricular and supraoptic nuclei.

    Science.gov (United States)

    Benrick, A; Schéle, E; Pinnock, S B; Wernstedt-Asterholm, I; Dickson, S L; Karlsson-Lindahl, L; Jansson, J-O

    2009-07-01

    Interleukin (IL)-6 is a pro-inflammatory cytokine that also affects metabolic function because IL-6 depleted (IL-6(-/-)) mice develop late-onset obesity. IL-6 appears to act in the central nervous system, presumably in the hypothalamus, to increase energy expenditure that appears to involve stimulation of the sympathetic nervous system. In the present study, we explored possible central mechanisms for the effects exerted by IL-6 on body fat. Therefore, we measured the effects of IL-6 depletion in IL-6(-/-) mice on expression of key hypothalamic peptide genes involved in energy balance by the real time polymerase chain reaction. Additionally, co-localisation between such peptides and IL-6 receptor alpha was investigated by immunohistochemistry. IL-6 deficiency decreased the expression of several peptides found in the paraventricular nucleus (PVN), which is a nucleus that has been attributed an adipostatic function. For example, corticotrophin-releasing hormone (CRH), which is reported to stimulate the sympathetic nervous system, was decreased by 40% in older IL-6(-/-) mice. Oxytocin, which is reported to prevent obesity, was also decreased in older IL-6(-/-) animals, as was arginine vasopressin (AVP). The IL-6 receptor alpha was abundantly expressed in the PVN, but also in the supraoptic nucleus, and was shown to be co-expressed to a high extent with CRH, AVP, oxytocin and thyrotrophin-releasing hormone. These data indicate that depletion of endogenous IL-6, a body fat suppressing cytokine, is associated with the decreased expression of CRH and oxytocin (i.e. energy balance regulating peptides) as well as AVP in the PVN. Because IL-6 receptor alpha is co-expressed with CRH, oxytocin and AVP, IL-6 could stimulate the expression of these peptides directly.

  13. Interleukin-6 and diabetes: the good, the bad, or the indifferent?

    DEFF Research Database (Denmark)

    Kristiansen, Ole P; Mandrup-Poulsen, Thomas

    2005-01-01

    Inflammatory mechanisms play a key role in the pathogenesis of type 1 diabetes. Individuals who progress to type 2 diabetes display features of low-grade inflammation years in advance of disease onset. This low-grade inflammation has been proposed to be involved in the pathogenetic processes...... been proposed to affect glucose homeostasis and metabolism directly and indirectly by action on skeletal muscle cells, adipocytes, hepatocytes, pancreatic beta-cells, and neuroendocrine cells. Here we argue that IL-6 action-in part regulated by variance in the IL-6 and IL-6alpha receptor genes...

  14. Persistence of interleukin 7 activity and levels on tumour necrosis factor alpha blockade in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    van Roon, Joel A. G.; Hartgring, Sarita A. Y.; Wijk, Marion Wenting-van; Jacobs, Kim M. G.; Tak, Paul-Peter; Bijlsma, Johannes W. J.; Lafeber, Floris P. J. G.

    2007-01-01

    Objectives: To identify the mechanism of interleukin (IL)7-stimulated tumour necrosis factor alpha (TNF alpha) production and to determine the relationship between intra-articular IL7 and TNF alpha expression levels in patients with rheumatoid arthritis ( RA). In addition, the effect of TNF alpha bl

  15. Regulation of ciliary neurotrophic factor receptor alpha in sciatic motor neurons following axotomy.

    Science.gov (United States)

    MacLennan, A J; Devlin, B K; Neitzel, K L; McLaurin, D L; Anderson, K J; Lee, N

    1999-01-01

    Spinal motor neurons are one of the few classes of neurons capable of regenerating axons following axotomy. Injury-induced expression of neurotrophic factors and corresponding receptors may play an important role in this rare ability. A wide variety of indirect data suggests that ciliary neurotrophic factor receptor alpha may critically contribute to the regeneration of injured spinal motor neurons. We used immunohistochemistry, in situ hybridization and retrograde tracing techniques to study the regulation of ciliary neurotrophic factor receptor alpha in axotomized sciatic motor neurons. Ciliary neurotrophic factor receptor alpha immunoreactivity, detected with two independent antisera, is increased in a subpopulation of caudal sciatic motor neuron soma one, two and six weeks after sciatic nerve transection and reattachment, while no changes are detected at one day and 15 weeks post-lesion. Ciliary neurotrophic factor receptor alpha messenger RNA levels are augmented in the same classes of neurons following an identical lesion, suggesting that increased synthesis contributes, at least in part, to the additional ciliary neurotrophic factor receptor alpha protein. Separating the proximal and distal nerve stumps with a plastic barrier does not noticeably affect the injury-induced change in ciliary neurotrophic factor receptor alpha regulation, thereby indicating that this injury response is not dependent on signals distal to the lesion traveling retrogradely through the nerve or signals generated by axonal growth through the distal nerve. The prolonged increases in ciliary neurotrophic factor receptor alpha protein and messenger RNA found in regenerating sciatic motor neurons contrast with the responses of non-regenerating central neurons, which are reported to display, at most, a short-lived increase in ciliary neurotrophic factor receptor alpha messenger RNA expression following injury. The present data are the first to demonstrate, in vivo, neuronal regulation of

  16. Is male factor infertility associated with midlife low-grade inflammation?

    DEFF Research Database (Denmark)

    Hærvig, Katia Keglberg; Kierkegaard, Lene; Lund, Rikke

    2017-01-01

    Male factor infertility is associated with an increased risk of disease and mortality, which has been related to markers of chronic systemic inflammation. The objective of this study was to investigate the association between male factor infertility and low-grade inflammation and furthermore...... to examine the lifetime prevalence of male factor infertility and overall infertility (also including female and couple infertility). The study population consisted of 2140 members of the Metropolit 1953 Danish Male Birth Cohort who had participated in the Copenhagen Aging and Midlife Biobank data collection...... in 2009-2011. Information on male factor infertility and overall infertility was obtained from a questionnaire, and low-grade inflammation was evaluated as the highest plasma levels of C-reactive protein, interleukin-6 and tumour necrosis factor-alpha in the population. The level of interleukin-6...

  17. Salivary transforming growth factor alpha in patients with Sjögren's syndrome and reflux laryngitis

    Directory of Open Access Journals (Sweden)

    Marco Antonio dos Anjos Corvo

    2014-12-01

    Full Text Available Introduction: Saliva plays a key role in the homeostasis of the digestive tract, through its inorganic components and its protein growth factors. Sjögren's syndrome patients have a higher prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux. Decreased salivary transforming growth factor alpha levels were observed in dyspeptic patients, but there have been no studies in patients with Sjögren's syndrome and laryngopharyngeal reflux. Objective: To compare the salivary transforming growth factor alpha levels of patients with Sjögren's syndrome and laryngopharyngeal reflux to those of healthy controls. Methods: This is a prospective controlled study. Twelve patients with Sjögren's syndrome and laryngopharyngeal reflux and 11 controls were prospectively evaluated. Spontaneous and stimulated saliva samples were obtained to establish salivary transforming growth factor alpha concentrations. Results: The salivary transforming growth factor alpha levels of patients were significantly higher than those of healthy controls. Five patients with laryngopharyngeal reflux also had erosive esophagitis; their salivary transforming growth factor alpha levels were comparable to controls. Conclusion: Salivary transforming growth factor alpha level was significantly higher in patients with Sjögren's syndrome and laryngopharyngeal reflux when compared to the control group.

  18. Suppression of estrogen receptor-alpha transactivation by thyroid transcription factor-2 in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eunsook; Gong, Eun-Yeung [Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Romanelli, Maria Grazia [Department of Life and Reproduction Sciences, University of Verona, Strada le Grazie 8, 37134 Verona (Italy); Lee, Keesook, E-mail: klee@chonnam.ac.kr [Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer TTF-2 was expressed in mammary glands and breast cancer cells. Black-Right-Pointing-Pointer TTF-2 repressed ER{alpha} transactivation. Black-Right-Pointing-Pointer TTF-2 inhibited the proliferation of breast cancer cells. -- Abstract: Estrogen receptors (ERs), which mediate estrogen actions, regulate cell growth and differentiation of a variety of normal tissues and hormone-responsive tumors through interaction with cellular factors. In this study, we show that thyroid transcription factor-2 (TTF-2) is expressed in mammary gland and acts as ER{alpha} co-repressor. TTF-2 inhibited ER{alpha} transactivation in a dose-dependent manner in MCF-7 breast cancer cells. In addition, TTF-2 directly bound to and formed a complex with ER{alpha}, colocalizing with ER{alpha} in the nucleus. In MCF-7/TTF-2 stable cell lines, TTF-2 repressed the expression of endogenous ER{alpha} target genes such as pS2 and cyclin D1 by interrupting ER{alpha} binding to target promoters and also significantly decreased cell proliferation. Taken together, these data suggest that TTF-2 may modulate the function of ER{alpha} as a corepressor and play a role in ER-dependent proliferation of mammary cells.

  19. Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

    Science.gov (United States)

    Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

    1999-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

  20. Intragraft platelet-derived growth factor-alpha and transforming growth factor-beta1 during the development of accelerated graft vascular disease after clinical heart transplantation

    NARCIS (Netherlands)

    de Groot-Kruseman, H A; Baan, C C; Mol, W M; Niesters, H G; Maat, A P; Balk, A H; Weimar, W

    1999-01-01

    This study was to determine whether the growth factors platelet-derived growth factor-alpha (PDGF-alpha) and transforming growth factor-beta1 (TGF-beta1) contribute to the development of graft vascular disease (GVD) after clinical heart transplantation. We analysed intragraft PDGF-alpha and TGF-beta

  1. Epigenetic modifications of interleukin-6 in synovial fibroblasts from osteoarthritis patients

    Science.gov (United States)

    Yang, Fei; Zhou, Song; Wang, Chuandong; Huang, Yan; Li, Huiwu; Wang, You; Zhu, Zhenan; Tang, Jian; Yan, Mengning

    2017-01-01

    Osteoarthritis (OA) is the most common degenerative disease of the synovial joint. The synovial membrane is responsible for the inflammatory reaction leading to the secretion of macrophage-derived pro-inflammatory cytokines, such as IL-6. Suppressing IL-6 over-expression in synovial fibroblasts (SF) is a promising method to prevent OA development and progression, in which the prerequisite is the elucidation of the molecular mechanisms underlying IL-6 over-expression in SF. Currently, there are few reports concerning epigenetic modifications in IL-6 in OA SF. In the present study, we attempted to investigate this phenomenon. SF over-expressing IL-6 was collected from OA patients. DNA hypomethylation and histone hyperacetylation were observed in the IL-6 promoter regions in OA SF compared with normal SF. No differences in the status of H3K9 di-methylation, H3K27 tri-methylation and H3K4 tri-methylation were observed in the IL-6 promoter regions between normal and OA SF. DNA (cytosine-5-)-methyltransferase 3 alpha (Dnmt3a) overexpression and anacardic acid (histone acetyltransferase inhibitor) treatment increased DNA methylation and decreased histone acetylation in the IL-6 promoter, and IL-6 over-expression in OA SF was suppressed. These observations provide deeper insight into the pathogenesis of OA and can be used to design new drugs and develop new therapeutic methods to treat OA. PMID:28262826

  2. Effect of vitamin D therapy on interleukin-6, visfatin, and hyaluronic acid levels in chronic hepatitis C Egyptian patients

    Directory of Open Access Journals (Sweden)

    Sabry D

    2015-02-01

    Full Text Available Dina Sabry,1 Mohamed AS Al-Ghussein,2 Gehan Hamdy,3 Amr Abul-Fotouh,4 Tarek Motawi,5 Amany Y El Kazaz,6 Ahmed Eldemery,7 Marwa Shaker8,9 1Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Giza, Egypt; 2Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Gaza, State of Palestine, 3Internal Medicine Department, 4Tropical Medicine Department, Faculty of Medicine, 5Biochemistry Department, Faculty of Pharmacy, Cairo University, Giza, Egypt; 6Medical Biochemistry Department, Faculty of Medicine, Suez Canal University, Ismaileya, Egypt; 7Medical Biochemistry Department, Faculty of Medicine, October 6 University, Giza, Egypt; 8Tropical Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt; 9Tropical Medicine Department, Bny Swif University, Bny Swif, Egypt Objectives: We aimed to compare serum levels of interleukin-6, visfatin, and hyaluronic acid in chronic hepatitis C Egyptian patients who received standard of care (SOC therapy for chronic hepatitis C virus (HCV consisting of pegylated interferon (PEG-IFN and ribavirin (RBV and in those who received SOC with vitamin D (vit D for 48 weeks in HCV genotype 4a subjects. Design and methods: One hundred chronic HCV patients were classified into two groups: study 50 patients received SOC therapy PEG-IFN/RBV + vit D and control 50 patients received SOC PEG-IFN/RBV without vit D. Both groups were followed up at 12 weeks, 24 weeks, and 48 weeks of treatment. Results: Results showed a significant elevation in vit D levels in the group treated with SOC and vit D compared to SOC group and a reduction in HCV RNA from the 12th week to reach zero level in the 24th week. Interleukin-6, visfatin, and hyaluronic acid levels were also reduced significantly. Alanine transaminase and aspartate transaminase biomarkers were significantly reduced, indicating decreased liver injury. Conclusion: SOC PEG-IFN/RBV + vit D therapy for chronic HCV led

  3. Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression.

    Science.gov (United States)

    Freedman, R; Wetmore, C; Strömberg, I; Leonard, S; Olson, L

    1993-05-01

    The nicotinic cholinergic antagonist alpha-bungarotoxin (alpha-BT) binds throughout the rat hippocampal formation. The binding is displaceable by d-tubocurarine. The most heavily labeled cells are GABA-containing interneurons in the dentate and in Ammon's horn. These neurons have several different morphologies and contain several neuropeptides. alpha-BT-labeled interneurons in the dentate are small cells between the granular and molecular layers that often contain neuropeptide Y. alpha-BT-labeled interneurons in CA1 are medium-sized interneurons, occasionally found in stratum pyramidale, but more often found in stratum radiatum and stratum lacunosum moleculare. These neurons often contain cholecystokinin. The largest alpha-BT-labeled interneurons are found in CA3, in both stratum radiatum and stratum lucidum. These neurons are multipolar and frequently are autofluorescent. They often contain somatostatin or cholecystokinin. These large interneurons have been found to receive medial septal innervation and may also have projections that provide inhibitory feedback directly to the medial septal nucleus. The cholinergic innervation of the hippocampus from the medial septal nucleus is under the trophic regulation of NGF and brain-derived neurotrophic factor, even in adult life. Expression of mRNA for both these factors is increased in CA3 and the dentate after intraventricular administration of alpha-BT, but not after administration of the muscarinic antagonist atropine. alpha-BT-sensitive cholinergic receptors on inhibitory interneurons may be critical to medial septal regulation of the hippocampal activity, including the habituation of response to sensory input.

  4. The effects of retinoic acid on immunoglobulin synthesis: Role of interleukin 6

    Energy Technology Data Exchange (ETDEWEB)

    Ballow, M.; Xiang, Shunan; Wang, Weiping; Brodsky, L. [Children`s Hospital of Buffalo, NY (United States)]|[State Univ. of New York, Buffalo, NY (United States)

    1996-05-01

    Retinoic acid (RA) and its parent compound, retinol (ROH, vitamin A), have been recognized as important immunopotentiating agents. Previous studies from our laboratory have demonstrated that PA can augment formalin-treated Staphylococcus aureus (SAC) stimulated immunoglobulin (Ig) synthesis of cord blood mononuclear cells (CBMC). To determine the mechanism(s) by which RA modulates Ig synthesis, we studied the effects of RA on B cells and cytokine production. The addition of RA (10{sup -5} to 10{sup -10} M) to Epstein-Barr virus (EBV)-transformed B-cell clones derived from either adult or cord blood B cells augmented Ig secretion twofold. In contrast, cell proliferation was inhibited as measured by {sup 3}H-thymidine incorporation. We evaluated two cytokines known to be constitutively produced by EBV cell lines, IL-1 and IL-6. While RA had no effect on IL-1 production, IL-6 synthesis was greatly enhanced (20- to 45-fold), which was also reflected by an increase in steady-state mRNA levels for IL-6 but not TNF-{alpha} or TGF-{beta} on Northern blot analysis. Polyclonal rabbit anti-IL-6 antibodies were used to block the augmenting effects of RA on Ig synthesis of adenoidal B cells. RA-induced augmentation in IgG and IgA synthesis was blocked 58 and 29%, respectively, by anti-IL-6 antibodies. These studies suggest that the enhancing effects of RA on Ig synthesis are mediated, at least in part, by the autocrine or paracrine effects of IL-6 on B-cell differentiation. 37 refs., 5 figs.

  5. Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production.

    Science.gov (United States)

    Bowers, Laura W; Brenner, Andrew J; Hursting, Stephen D; Tekmal, Rajeshwar R; deGraffenried, Linda A

    2015-01-01

    Obesity is associated with a worse breast cancer prognosis, particularly in estrogen receptor alpha (ERα) positive, postmenopausal patients. We hypothesized that this is mediated in part by an elevation in breast cancer cell cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production that results in greater local pre-adipocyte aromatase expression. We utilized an in vitro model of the obese patient's tumor microenvironment in which cultured MCF-7 breast cancer cells and pre-adipocytes were exposed to pooled serum from obese (OB; BMI ≥ 30.0 kg/m(2)) or normal weight (N; BMI 18.5-24.9 kg/m(2)) postmenopausal women. Exposure to OB versus N sera significantly increased MCF-7 cell COX-2 expression and PGE2 production. Pre-adipocyte aromatase expression was 89 % greater following culture in conditioned media (CM) from MCF-7 cells exposed to OB versus N sera (OB-CM and N-CM, respectively), a difference nullified by MCF-7 cell treatment with the COX-2 inhibitor celecoxib. Previous analysis of the sera revealed significantly higher interleukin-6 (IL-6) concentrations in the OB versus N samples. Depletion of IL-6 from the sera neutralized the difference in pre-adipocyte aromatase expression stimulated by OB-CM versus N-CM. Finally, CM from pre-adipocyte/MCF-7 cell co-cultures exposed to OB sera stimulated greater MCF-7 and T47D breast cancer cell ERα activity and proliferation in comparison to N sera. This study indicates that obesity-associated systemic IL-6 indirectly enhances pre-adipocyte aromatase expression via increased breast cancer cell PGE2 production. Investigation regarding the efficacy of a COX-2 inhibitor/aromatase inhibitor combination therapy in the obese postmenopausal patient population is warranted.

  6. Alpha Decay Preformation Factors for Even-Even 280-316116 Superheavy Isotopes

    Science.gov (United States)

    Alsaif, Norah A. M.; Radiman, Shahidan; Yahaya, Redzuwan; Ahmed, Saad M. Saleh

    2016-06-01

    The success of the cluster formation model (CFM) in deriving an energy-dependent formula for the preformation factors of heavy nuclei has motivated us to expand this approach to the superheavy isotopes (SHI). In this paper, the alpha-cluster formation (preformation factor) behavior inside the parent nuclei of SHI with atomic number Z = 116 and neutron numbers 164 ≤ N ≤ 200 is determined using the alpha preformation formula contained within the CFM. The cluster formation energy of the alpha particles and the total energy of the parent nuclei are calculated on the basis of the various binding energies. Our results clearly show that the CFM remains valid for superheavy nuclei (SHN). In addition, our calculations reveal that the alpha clustering mechanism and formation probability in 280-316116 even-even SHI are similar to those of even-even heavy nuclei in a general sense.

  7. Astrophysical S factor for {alpha}-capture on {sup 115}Sn

    Energy Technology Data Exchange (ETDEWEB)

    Filipescu, D.; Cata-Danil, I.; Ivascu, M.; Bucurescu, D.; Zamfir, N.V.; Glodariu, T.; Stroe, L.; Mihai, C.; Marginean, N.; Ghita, D.G.; Marginean, R.; Suliman, G.; Sava, T.; Pascu, S. [Horia-Hulubei National Institute for Physics and Nuclear Engineering, Magurele-Ilfov (Romania); Cata-Danil, G. [Physics Department, University Politehnica, Bucharest (Romania)

    2009-07-01

    The s and r processes calculations can only account for 50% of the {sup 115}Sn abundance, and recent p process calculations cannot explain the remaining fraction. For this reason, the experimental measurement of the S factor of {alpha} capture on {sup 115}Sn is of high importance in explaining the origin of {sup 115}Sn. The cross section of {sup 115}Sn({alpha}, {gamma}){sup 119}Te reaction has been measured in the effective center of mass energy from 9.5 to 14.7 MeV. Enriched self-supporting {sup 115}Sn (56%) foils were bombarded with {alpha} beam delivered by the Bucharest IFIN-HH Tandem Accelerator. The induced activity of {sup 119}Te was measured with two large volume GeHP detectors in close geometry to maximize the detector efficiency. The experimental cross section and astrophysical S factor are compared with statistical model predictions for different global {alpha}-nucleus optical potential.

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

    Science.gov (United States)

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

    2000-03-01

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

  9. Colchicine Inhibited the Expression of Tissue Inhibitor of Metalloprotenase-1 and Interleukin-6 in Cultured Activated Hepatic Stellate Cells

    Institut