Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Supplementary vitamin C (2 x 500 mg tablets daily) or a matched placebo was administered to 10 and 6 ultramarathon athletes respectively for 7 days prior to participation in a 90 kilometer running event, as well as on the day of the race and for 2 days after its completion. Circulating concentrations of vitamins A, C and E, as well as those of leukocytes and platelets, myeloperoxidase, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF), cortisol, and creatine kinase were measured 16 hours before the race and at 30 min, 24 hours, and 48 hours after completion. Pre-race vitamin C concentrations in the supplemented group were unchanged after the race (118.2 +/- 15.9 and 115.9 +/- 11.9 micromol/l) while an increase was observed in the placebo group immediately post-race (85.8 +/- 11.9 to 107.4 +/- 18.8 micromol), with a return to pre-race values after 24 hours. Immediately on completion of the race transient elevations occurred in the concentrations of circulating neutrophils, monocytes and platelets, IL-6, cortisol, CRP, and creatine kinase in both groups. In the supplemented group the concentrations of CRP were significantly higher (p < 0.01) at each of the post-race time-points while those of cortisol were 30% lower immediately post-race. These observations provide evidence that supplementation with vitamin C may blunt the adaptive mobilization of this vitamin from the adrenals during exercise-induced oxidative stress and may be associated with an enhancement of the acute phase protein response and attenuation of the exercise-induced increase in serum cortisol.
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PMID:Attenuation of increase in circulating cortisol and enhancement of the acute phase protein response in vitamin C-supplemented ultramarathoners. 1128 14

The aim of this study was to evaluate the diagnostic capacity of a number of blood components such as soluble adhesion molecules, interleukin-6 (IL-6), myeloperoxidase (MPO) and lysozyme in the distinction of acute bacterial and viral infections. Blood was taken from 115 acutely infected patients at admission before any treatment and in some cases on several consecutive days. 35 of the patients had a definite viral cause for their infection and 66 a bacterial cause. All variables were raised in patients with acute bacterial infections. Soluble vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, lysozyme and MPO were also raised in acute viral infections, but for sE-selectin and MPO less so than in bacterial infections. Evaluation of the diagnostic power showed that for MPO and IL-6 at cut-offs of 1300 microg/l and 100 ng/l, respectively, the positive predictive value was 97% and 100% and the negative predictive value 78% and 76%, respectively, in the classification of acute bacterial infections. In the distinction between viral or bacterial causes of acute infections in otherwise healthy subjects serum measurements of MPO and IL-6 are valuable tools and should be considered as diagnostic aids in the routine setting. The soluble adhesion molecules did not offer any further information in this respect.
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PMID:Soluble adhesion molecules, cytokines and cellular markers in serum in patients with acute infections. 1134 22

It has been shown that human thyrocytes can synthesize cytokines which activate T and B lymphocytes. These immune cells play important roles in the initiation and continuation of thyroid autoimmunity. The aim of this study was to estimate serum concentrations of soluble interleukin-6 receptor (sIL-6R), interleukin-6 (IL-6) and interleukin-8 (IL-8) in patients with Graves' disease (GD) (n=44, mean age 14.8 years), in patients with nontoxic nodular goiter (NTNG) (n=36, mean age 15.6 years) and in a group of healthy controls (n=20, mean age 14.5 years). ELISA was used to determine the concentration of cytokines, antithyroglobulin and antithyroid peroxidase antibodies in patients with thyroid disease. Radio receptor assay (RRA) was performed to detect anti-TSH receptor autoantibodies (TRAb). Serum levels of IL-6, sIL-6R and IL-8 were markedly elevated in patients with GD before treatment with methimazole (p<0.0001 for IL-6, p<0.006 for sIL-6R, p<0.004 for IL-8) and after 8 weeks of therapy (p<0.011 for IL-6, p<0.04 for IL-8). However, following 24 months of treatment, normal serum concentrations of these cytokines were restored. Furthermore, patients with NTNG showed a slightly elevated concentration of cytokines (IL-6, IL-8). Serum levels of tri-iodothyronine in patients with GD positively correlated with serum concentrations of IL-6 (r = 0.35, p<0.025) and sIL-6R (r = 0.31, p<0.047), while no correlation was found between thyroxine and cytokines. Moreover, we observed a positive correlation between serum levels of TPO-Abs, TRAb and IL-6 (r = 0.43, p<0.008; r = 0.5, p<0.003) and between TPO-Abs and IL-8 (r = 0.67, p<0.0001). However, in patients with NTNG no correlation was observed between serum levels of antithyroid antibodies or thyroid hormones and serum levels of cytokines. We conclude that the cytokines (IL-6, sIL-6R, IL-8) could play an important role in the development of Graves' disease and that their levels are modulated by thyreostatic treatment.
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PMID:Serum levels of cytokines in children and adolescents with Graves' disease and non-toxic nodular goiter. 1145 24

WF10 is a chlorite-based drug that modulates macrophages functional states and can be safely administered to humans. WF10 potentially modulates disease-related up-regulation of immune responses both in vitro and in vivo. Thus immune response is influenced in a way that inappropriate inflammatory reactions are downregulated. The molecular mechanisms involved are not completely understood. Biochemical data suggest the reaction of chlorite with hemoproteins as the central step in the activation process of the drug. Thereby a chlorinating agent is generated, resulting in the oxidation of reduced sulfur-containing molecules and in the conversion of amino residues into more or less stable chloramines. The most prominent chloramine in vivo is taurine chloramine. Taurine chloramine is a long-lived molecule with immunomodulatory properties. For instance, taurine chloramine inhibits the generation of macrophage inflammatory mediators such as nitric oxide, prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). This study on the biochemical mechanism of WF10 gives evidence that hemoprotein dependent chlorination of taurine is not only observed in vitro but also very likely in vivo. To characterize the oxidant, generated during heme activation, different methods were used: Chemiluminescence, EPR-spectroscopy, UV/VIS-spectroscopy, gas (GC) and size exclusion chromatography. In summary, the results indicate as the first products of hemoprotein catalyzed chlorite activation a chloroxygen-species (probably HOCl/OCl-) and a ferryl-oxygen species at the hemoprotein active site in analogy to the known peroxidase (compound I and II) intermediates. Moreover, hydrogen peroxide and chlorite seem to react in a similar way with heme centers. It is proposed that WF10 represents an "inactive" transport form of potentially active chlorine. Reactivity of the latter is restricted unless heme moieties in proteins or enzymes activate the "transport form" to perform reactions in analogy to peroxidases (i.e. myeloperoxidase-catalyzed formation of HOCl/OCl-).
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PMID:Chlorite-hemoprotein interaction as key role for the pharmacological activity of the chlorite-based drug WF10. 1150 86

There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH), creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2alpha; 8-Iso-PGF2alpha) and antioxidant enzyme activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid hydroperoxides and 8-Iso-PGF2alpha 2 d after the exercise. This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress.
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PMID:Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. 1155 12

Hepatic cytochrome P450 (CYP) expression and antioxidant activity have been shown to decrease following endotoxin (lipopolysaccharide [LPS]) or proinflammatory cytokine administration. Using mice deficient in interleukin-6 (IL-6), the role of IL-6 in the regulation of hepatic CYP activity, glutathione (GSH) metabolism, and catalase (CAT) activity was analyzed after LPS administration. Administration of LPS produced comparable decreases in hepatic CYP3A activity in WT B6x129 (WT) mice and IL-6 knockout mice. No decrease was observed for CYP2D9 activity after LPS administration in either WT or IL-6 knockout mice. LPS administration significantly increased hepatic and renal CYP2E1 and CYP4A activity in WT mice, with no effect in IL-6 knockout mice. CYP2A12 activity increased in IL-6 knockout, mice with no change in WT mice after LPS administration. LPS administration had no significant effect on hepatic GSH reductase, GST peroxidase, GSH-S-transferase (GST), or total GSH in either WT or IL-6 knockout. However, hepatic CAT activity was significantly reduced in WT mice after LPS administration, with no effect in IL-6 knockout mice. These results support IL-6 as a critical mediator of the effects of LPS on specific hepatic and renal CYP activities and hepatic CAT activity.
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PMID:Cytochrome P450 and antioxidant activity in interleukin-6 knockout mice after induction of the acute-phase response. 1171 Sep 94

Laparoscopy to treat abdominal infections is becoming more and more popular. The effects of the CO(2) pneumoperitoneum have not yet been completely clarified. In a rat peritonitis model, therefore, we investigated the influence of laparoscopic lavage in comparison with the conventional technique. A defined multibacterial fecal specimen was installed in the abdominal cavities of 80 rats. These animals were randomized to three groups: group 1 (n = 32), no intervention; group 2 (n = 24), conventional; group 3 (n = 24), laparoscopic lavage. At 1, 2, and 8 hours after the surgical intervention, animals were killed and autopsied. The main outcome measures were bacteremia, interleukin-6 (IL-6) in plasma and ascites, changes in the blood count, and myeloperoxidase (MPO) activity in lung, liver, kidney, and pancreas. Differences of bacteremia were not found. In the ascites a marked increase in IL-6 was observed after 8 hours, which was lower in the treatment groups than in the controls (p <0.025). MPO activity as a measure of the granulocytes present in the tissue showed significant changes only in lung tissue. Two hours after the surgical intervention, the MPO in the lung in the laparoscopy group was significantly lower than that in the controls and the laparotomy group. In conclusion, conventional and laparoscopic lavage reduce inflammation. In this model, laparoscopic lavage with a CO(2) pneumoperitoneum appeared to have no negative influence on the inflammatory reaction during the early postoperative phase. Reduced neutrophil sequestration in lung tissue following laparoscopic lavage reflects the lower level of trauma caused by laparoscopy.
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PMID:Reduced neutrophil sequestration in lung tissue after laparoscopic lavage in a rat peritonitis model. 1189 33

Interleukin-10 (IL-10) exerts a wide spectrum of regulatory activities in the immune and inflammatory response. The aim of this study was to investigate the role of endogenous IL-10 on the modulation of the inflammatory response in mice subjected to carrageenan-induced lung injury. When compared to carrageenan-treated IL-10 wild-type (WT) mice, carrageenan-treated IL-10 knock-out mice (IL-10KO) mice experienced a higher rate of pleural exudation, and polymorphonuclear cell migration. Exudate levels of the pro-inflammatory cytokines tumour necrosis factor, interleukin-1beta and interleukin-6 were also greatly enhanced in IL-10KO mice in comparison to wild-type mice. Lung myeloperoxidase (MPO) activity was significantly reduced in IL-10WT mice when compared to IL-10KO mice-treated with carrageenan. The degree of oxidative and nitrosative damage was significantly higher in IL-10KO mice than in wild-type littermates, as indicated by elevated malondialdehyde levels and formation of nitrotyrosine and poly (ADP-ribose) synthetase (PARS). Staining of lung tissue sections obtained from carrageenan-treated IL-10WT with an anti-COX-2 antibody showed a positive staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase (iNOS) was found mainly in the macrophages of the inflamed lungs from carrageenan-treated IL-10WT mice. The intensity and degree of the staining for COX-2 and iNOS were markedly enhanced in tissue sections obtained from carrageenan-treated IL-10KO mice. Most notably, the degree of lung injury caused by carrageenan was also enhanced in IL-10KO mice. Taken together, our results clearly demonstrate that endogenous IL-10 exerts an anti-inflammatory role during acute inflammation and tissue damage associated with carrageenan-induced pleurisy, possibly by regulating neutrophil recruitment, and the subsequent cytokine and oxidant generation.
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PMID:Absence of endogenous interleukin-10 enhances the evolution of acute lung injury. 1223 72

Mesenteric ischemia-reperfusion injury is a serious complication of shock. Because activation of nuclear factor-kappaB (NF-kappaB) has been implicated in this process, we treated rats with vehicle or the IkappaB-alpha inhibitor BAY 11-7085 (25 mg/kg ip) 1 h before mesenteric ischemia-reperfusion (45 min of ischemia followed by reperfusion at 30 min or 6 h) and examined the ileal injury response. Vehicle-treated rats subjected to ischemia-reperfusion exhibited severe mucosal injury, increased myeloperoxidase (MPO) activity, increased expression of interleukin-6 and intercellular adhesion molecule 1 protein, and a biphasic peak of NF-kappaB DNA-binding activity during the 30-min and 6-h reperfusion courses. In contrast, BAY 11-7085-pretreated rats subjected to ischemia-reperfusion exhibited less histological injury and less interleukin-6 and intercellular adhesion molecule 1 protein expression at 30 min of reperfusion but more histological injury at 6 h of reperfusion than vehicle-treated rats subjected to ischemia-reperfusion. Studies with phosphorylation site-specific antibodies demonstrated that IkappaB-alpha phosphorylation at Ser(32),Ser(36) was induced at 30 min of reperfusion, whereas tyrosine phosphorylation of IkappaB-alpha was induced at 6 h of reperfusion. BAY 11-7085 inhibited the former, but not the latter, phosphorylation pathway, whereas alpha-melanocyte-stimulating hormone, which is effective in limiting late ischemia-reperfusion injury to the intestine, inhibited tyrosine phosphorylation of IkappaB-alpha. Thus NF-kappaB appears to play an important role in the generation and resolution of intestinal ischemia-reperfusion injury through different activation pathways.
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PMID:Effects of NF-kappa B inhibition on mesenteric ischemia-reperfusion injury. 1246 47

Metallothioneins (MT) are ubiquitous found in eukaryotic organism. MT have a potential for metal-storage and protect the cells against stress. On the genomic level, proinflammatory cytokines like interleukin-6 and transition metals like copper cause induction of MT. Therefore, an estimation of MT in liver-biopsies from patients with different diseases probably could help in identifying acute-phase reactions and processes which lead to increased copper. We investigated paraffin embedded liver biopsies from 170 patients and 13 control biopsies from cases of sudden death. Tissue was stained with a primary antibody against MT and a peroxidase technique was used to make results visible. A grading was performed using an immunoreactive score (IRS from 0-24) and by computer-aided measurement of the optical density (OD) of the stained tissue slides. Patients with cholestasis (IRS: 12.1 +/- 2.8, n = 11), autoimmune (10.6 +/- 3.1, n = 7) or inflammatory bowel diseases (IBD) (13.3 +/- 5.1, n = 4) and lymphoma (9.8 +/- 5.8, n = 21) showed marked increases in MT compared to the controls (5.2 +/- 2.8, n = 13). Patients with chronic hepatitis B or C or chronic alcoholic abuse had no elevation of MT. Furthermore, no correlation was found between histological damage and amount of MT except in cases of cholestasis, in which increased MT was observed. Results by OD confirmed the findings. In summary, we were able to demonstrate a clear increase of MT content in liver-biopsies in proinflammatory and cholestatic conditions. Marked elevation in patients with systemic diseases (like autoimmune-, IBD and lymphoma) seems to be best explained by an acute-phase induction of MT by proinflammatory cytokines. This could help in identifying these conditions in liver biopsies.
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PMID:Metallothionein in liver-biopsies from patients with different diseases. 1248 63


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