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)

Interleukin-6 (hepatocyte stimulating factor) is a 26 kd cytokine that plays a major role in the acute phase response, especially the hepatic aspects of the acute phase response. Patients with alcoholic hepatitis manifest many aspects of the acute phase response. In this 6-month study we evaluated serial plasma interleukin-6 levels in 30 consecutive patients with moderate to severe alcoholic hepatitis. Mean admission plasma interleukin-6 activity was markedly increased (49.8 +/- 8.5 U/ml, normal less than 5 U/ml) in patients with alcoholic hepatitis, and levels decreased with clinical improvement to 15.6 +/- 6.1 U/ml at 6 months. Admission interleukin-6 activity correlated significantly (r = 0.82) with the severity of liver disease as assessed by the discriminant function of Maddrey. Also measured were selected assays postulated to be regulated by interleukin-6, including serum albumin (2.3 +/- 0.1 gm/dl), which was significantly depressed; alpha 1-acid glycoprotein (52 +/- 5 mg/dl), which was within normal limits; and IgA (827 +/- 70 mg/dl) and C-reactive protein (3.03 +/- 0.51 mg/dl), which were significantly elevated. Interleukin-6 activity fell over time in a pattern similar to that of bilirubin and C-reactive protein. We suggest that plasma interleukin-6 may not only regulate many aspects of the acute phase response but also may be a marker of inflammation and severity of disease in alcoholic hepatitis.
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PMID:Increased plasma interleukin-6 concentrations in alcoholic hepatitis. 158 11

Although altered cytokine homeostasis has been implicated in the pathogenesis of alcoholic liver disease, the relationship between cytokines and metabolic consequences of alcoholic liver disease is unknown. We, therefore, sought to correlate circulating concentrations of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 to clinical and biochemical parameters of liver disease in chronic alcoholic patients. We used an enzyme-linked immunosorbent assay to measure plasma tumor necrosis factor and interleukin-1 and a bioassay to measure serum interleukin-6 in three groups of alcoholic men as follows: (a) actively drinking alcoholic men without evidence of chronic liver disease, (b) nondrinking alcoholic men with stable cirrhosis and (c) patients with acute alcoholic hepatitis. Mean cytokine concentrations were elevated in cirrhotic patients and alcoholic hepatitis patients compared with controls and alcoholic patients without liver disease. Tumor necrosis factor-alpha and interleukin-1 alpha concentrations remained elevated for up to 6 mo after diagnosis of alcoholic hepatitis, whereas interleukin-6 normalized in parallel with clinical recovery. Concentrations of all three cytokines were correlated with biochemical parameters of liver injury and hepatic protein synthesis plus serum immunoglobulin concentrations. We could not demonstrate a relationship between cytokine concentrations and peripheral endotoxemia. Percentages of peripheral blood monocytes that reacted with monoclonal antibodies to CD25 (interleukin-2 receptor) and human lymphocyte antigen-DR were similar for alcoholic patients and controls. These data suggest that tumor necrosis factor-alpha and interleukin-1 alpha are related to some of the metabolic consequences of both acute and chronic alcohol-induced liver disease, whereas interleukin-6 is related to abnormalities seen in acute liver injury.
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PMID:Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients. 199 37

Recent studies in alcoholic hepatitis have proposed a role for the cytokine tumour necrosis factor-alpha (TNF-alpha) a mediator of endotoxic shock in sepsis. In this study plasma levels of the closely related cytokine interleukin-6 (IL-6) were assayed in 96 samples from 58 patients with severe alcoholic hepatitis, and 69 patients in control groups (21 normal, 10 alcoholic without liver disease, 10 inactive alcoholic cirrhosis, 18 chronic liver disease, 10 chronic renal failure). Plasma IL-6 levels were markedly elevated in patients with alcoholic hepatitis when compared with all control groups (P less than 0.001). IL-6 levels were higher in patients who died (P = 0.04) and correlated with the features of severe disease including: increased grade of encephalopathy, increased neutrophil count, increased prothrombin ratio, hypotension, increased serum creatinine and increased serum bilirubin. Surprisingly, no correlation was found between levels of plasma IL-6 and plasma TNF-alpha or endotoxin, or the presence of infection; an inverse correlation was found between plasma IL-6 and serum globulins. These findings provide further evidence that the IL-6/TNF cytokine system is activated in severe alcoholic hepatitis and may mediate hepatic or extra-hepatic tissue damage.
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PMID:Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis. 204 24

Metallothioneins are attractive substances. One of the features of these proteins is the inducibility in response to heavy metals, to a great variety of metabolites and to stress factors. In mammalia, their synthesis may be induced by interleukin-6 in response to inflammation. Metallothionein could prevent renal toxicity of cDDP without compromising its anticancer activity. However, metallothionein is also implicated in the resistance to cDDP. There are now good evidences that metallothionein is involved in many diseases, such as inflammatory bowel disease, toxemia of pregnancy, liver disease, etc.
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PMID:[Metallothionein and medicine]. 760 19

Ascites is a readily available source of human macrophages (M phi), which can be used to study M phi functions in vitro. We characterized the mediators of inflammation produced by human peritoneal M phi (hp-M phi) obtained from patients with portal hypertension and ascites. The production of the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) was found to be lipopolysaccharide (LPS) concentration dependent (0-10 micrograms/ml) with a maximal production at 10 micrograms/ml and also dependent on the time of exposure to the stimulus (0-36 h). IL-1 beta, IL-6 and TNF-alpha production after LPS administration reached a plateau at 24 h. In vitro stimulation for 24 h with LPS does not influence the eicosanoid production from endogenous arachidonate. 13 min of exposure of the cells to the calcium ionophore A23187 gives a significant increase in eicosanoid production from both exogenous and endogenous arachidonate. The main eicosanoids produced are the 5-lipoxgenase products LTB4 and 5-hydroxyeicosatetraenoic acid (HETE). The increase in production of the other eicosanoids is not significant. The eicosanoid production depends on the stimulus concentration. The optimal A23187 concentration is 1 microM. Oxygen radical production was measured in the M phi by a flowcytometric method. The fluorescence intensity of phorbol 12-myristate 13-acetate stimulated and dihydro-rhodamine 123 loaded hp-M phi increases significantly after 15 min. We conclude that LPS stimulation of hp-M phi from liver disease results in similar production of IL-1 beta, IL-6 and TNF-alpha, but that the profile of the eicosanoid production of these M phi stimulated with LPS and A23187 differs from M phi of other origin and species.
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PMID:Production of inflammatory mediators by human macrophages obtained from ascites. 802 53

To elucidate the precise mechanism of carpal tunnel syndrome (CTS), serum hyaluronic acid (HA), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were measured in 71 chronic hemodialysis patients with or without CTS and/or shoulder pain. Patients were divided into two groups: Group 1 (n = 40) was the control group, and Group 2 (n = 31) patients had carpal tunnel syndrome, shoulder pain, or both. None of the patients had liver disease, rheumatoid arthritis, other inflammatory disease, or cancer. Serum HA concentrations in Groups 1 and 2 were 106.0 +/- 77.5 and 442.6 +/- 564.7 ng/dl (mean +/- SD), respectively. The difference between the groups was significant (p < 0.01). The serum concentrations of IL-6 in Group 1 were significantly lower than in Group 2 (p < 0.05); however, there was no significant difference in serum IL-1 beta and TNF-alpha levels. The mechanisms regulating in vivo synthesis of HA was obscure; however, in vitro studies suggest that inflammatory cytokines may stimulate an increased production of HA. In this study, CTS might be associated with increased serum concentrations of HA, and HA production might be mediated by IL-6.
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PMID:Serum hyaluronic acid and interleukin-6 as possible markers of carpal tunnel syndrome in chronic hemodialysis patients. 806 Feb 50

The existence of a cellular immune deficit in alcoholic cirrhosis, and the alterations described in cytokine synthesis in this disease, led us to compare serum concentrations of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 in a group of 33 patients with alcoholic cirrhosis (classified according to the Child-Pugh grade of severity of liver disease) and 43 healthy volunteers. Serum concentrations of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 were significantly raised in alcoholic cirrhosis patients, with no significant differences between patients with liver disease of different grades of severity. The results suggest that cirrhosis involves the activation of the monocyte-macrophage system, which may contribute to the progression of the disease and its clinical manifestations.
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PMID:Tumour necrosis factor, interleukin-1 and interleukin-6 in alcoholic cirrhosis. 835 43

The pathogenesis of chronic alcoholic liver disease is uncertain, but it may reflect an impaired wound healing response to ethanol-induced liver injury. Cell-to-cell communication such as that mediated by the cytokine tumor necrosis factor is necessary for successful liver regeneration and complete recovery from liver injury. Hence disruption of intercellular regenerative signaling may contribute to the pathogenesis of chronic alcoholic liver disease. To test this hypothesis, the cytokine and regenerative responses triggered by partial hepatectomy were compared in ethanol-fed rats and isocalorically maintained, pair-fed controls. To further clarify the effect of ethanol on tumor necrosis factor-modulated regenerative effects, we evaluated some of the rats in each feeding group after pretreatment with antibodies to tumor necrosis factor. As expected, ethanol inhibited DNA synthesis and liver cell proliferation after partial hepatectomy. Ethanol-associated inhibition of liver regeneration occurred despite apparently similar serum concentrations of the tumor necrosis factor-inducible cytokine interleukin-6. Treatment with antibodies to tumor necrosis factor 1 hr before partial hepatectomy inhibited post-partial hepatectomy induction of interleukin-6 and liver regeneration in ethanol-fed and pair-fed rats. However, serum interleukin-6 was reduced more in ethanol-fed rats than in control rats (93% vs. 66%; p < 0.05). Antibodies to tumor necrosis factor also inhibited hepatic DNA synthesis more in ethanol-fed rats than in controls (85% vs. 50%; p < 0.05). In ethanol-fed rats, the increased effect of tumor necrosis factor antibody on post-partial hepatectomy DNA synthesis suggests heightened sensitivity of hepatocytes to tumor necrosis factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term ethanol consumption alters the hepatic response to the regenerative effects of tumor necrosis factor-alpha. 851 56

Plasma levels of endotoxin and tumor necrosis factor alpha (TNF alpha) and the cytokine response of isolated monocytes were examined in chronic alcohol abusers with various degrees of liver disease. In 35 patients - 19 with alcoholic fatty liver (AF), 7 with alcoholic hepatitis (AH), 9 with cirrhosis (AC) - and in 15 healthy controls (HC), plasma levels of endotoxin were measured in the limulus assay, and plasma TNF alpha in an immunoassay. The cytokine response of monocytes stimulated in vitro with low doses of endotoxin (range: 25 pg/ml to 2.5 ng/ml) was determined in a cytolytic TNF bioassay and in TNF alpha and interleukin-6 (IL-6) immunoassays. All patient groups had elevated plasma endotoxin levels, whereas plasma TNF alpha was elevated only in AC (43.1 +/- 15.2 vs. HC: 5.0 +/- 1.1 pg/ml). Monocytes from all patient groups released increased amounts of bioactive TNF: AF 5.39 +/- 1.70, AH 7.10 +/- 3.28, AC 2.44 +/- 0.54 vs. HC 1.21 +/- 0.30 ng/ml (stimulation with 2.5 ng/ml endotoxin over 3 hrs.). Similar results were obtained in the TNF alpha immunoassay. Increased release of IL-6 from monocytes was shown only for AF, while values in AC were comparable to those in HC. These data confirm that endotoxemia is frequent in chronic alcoholics. In concert with an increased cytokine response of the monocyte/macrophage system, endotoxemia might contribute to the pathogenesis of alcoholic liver disease.
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PMID:Tumor-necrosis-factor and interleukin-6 response of peripheral blood monocytes to low concentrations of lipopolysaccharide in patients with alcoholic liver disease. 852 52

To assess the diagnostic and prognostic value of interleukin-6, interleukin 1 beta, and tumor necrosis factor-alpha assays in plasma and ascites, we measured these cytokines in eight patients with malignancy-related ascites and 32 patients with decompensated cirrhosis. Five patients had an episode of bacterial peritonitis, during which one or more ascitic fluid samples were analyzed. Interleukin-6 and tumor necrosis factor-alpha were not significantly different between the cirrhotic and the malignant groups: ascitic interleukin-6 13,816 +/- 15,314 vs 28,138 +/- 23,403 pg/ml, plasma interleukin-6 542 +/- 719 vs 559 +/- 604 pg/ml; ascitic tumor necrosis factor-alpha 19 +/- 50 vs 12 +/- 31 pg/ml, plasma tumor necrosis factor-alpha 3.4 +/- 8.2 vs 6.1 +/- 13.8 pg/ml. During an episode of bacterial peritonitis there was a significant increase only in ascitic interleukin-6 (133,268 +/- 99,743 pg/ml), which declined after antibiotic treatment. None of the parameters was associated with 6-month survival (11 of the 40 patients died within 6 months). There was a correlation (r = 0.675; p = 0.002) between plasma interleukin-6 levels and the Child-Pugh score in patients with cirrhosis, but not with the etiology of the liver disorder. Plasma interleukin-6 levels correlated with IgA levels (r = 0.649; p = 0.004) but not with C reactive protein, sedimentation rate, fibrinogen, IgM or IgG. These results do suggest that interleukin-6 is produced within the peritoneal cavity in hepatic and malignant ascites. There is a sharp increase in the local production of interleukin-6 during an episode of bacterial peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High interleukin-6 production within the peritoneal cavity in decompensated cirrhosis and malignancy-related ascites. 853 97


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