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)

Chronic alcoholism complicated by alcoholic liver disease (ALD) is characterized by activation of inflammatory responses. Alcohol intake increases gut permeability allowing substances such as lipopolysaccharides (LPS) which are strong inducers of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) to enter the circulation. Vitamin C is an antioxidant with many cellular activities seemed to protect cells against alcohol-induced peroxidation. In present study, serum levels of TNF-alpha and IL-6 were measured by ELISA method in four groups of albino rats, each group consists of 10 rats. Group (I) was untreated group (control), group (II) was treated with ethanol, group (III) was treated with ascorbic acid and group (IV) was treated with ethanol + ascorbic acid. Results revealed that both TNF-alpha and IL-6 serum levels were very highly significantly increased in group (II) and (IV) than control group (1) (P < 0.001). Group (III) showed significantly (P < 0.001) decreased TNF-alpha serum level than group (II) and (IV) while it showed significantly (P < 0.001) increased IL-6 serum level than control group (I) and also significantly decreased IL-6 serum level than group (IV). Serum IL-6 level was significantly (P < 0.01) decreased in group (III) than (II). These results indicate that serum levels of the proinflammatory cytokines TNF-alpha and IL-6 may serve as predictive biomarkers for progression of ALD. In addition, using TNF-alpha neutralizing agent (or its antagonist)/or IL-6 as an anti-apoptotic factor could be useful as a treatment strategy of ALD.
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PMID:Effects of chronic ethanol and vitamin C administration on production of tumor necrosis factor-alpha and interleukin-6 in rats. 1797 45

Hepatocyte apoptosis, inflammation, and fibrosis are prominent features of liver disease in general and of alcoholic liver injury in particular. Although the link between these processes remains unclear, one universal characteristic of liver injury is the induction of hepatocellular damage, which results in the generation of apoptotic bodies. Work from our laboratory over the last several years has studied the effect of ethanol administration on the process of apoptosis and a role for altered endocytosis in alcoholic apoptosis. We initially focused our research on the hepatocyte by examining endocytosis using the asialoglycoprotein receptor (ASGP-R) pathway as a model and we identified multiple ethanol-induced impairments in receptor function. We also showed that uptake of apoptotic bodies is impaired in hepatocytes isolated from ethanol-fed animals compared to controls, and that this impairment is linked to altered ASGP-R function. Recent work from our laboratory is examining a link between ethanol-impaired ASGP-R function, apoptotic body accumulation, and inflammation in the liver. We are particularly interested in data showing that factors produced by Kupffer cells incubated with apoptotic bodies can lead to production of tumor necrosis factor-alpha and interleukin-6, and that this effect is exacerbated in the setting of alcohol administration. In addition, we have preliminary data showing that media from Kupffer cell cultures incubated with apoptotic bodies can induce hepatocyte killing. The goal of our future work is to show that inadequate removal of apoptotic cells, in part via altered receptor-mediated endocytosis, plays a role in the course of pathogenesis of alcoholic liver injury.
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PMID:Impaired receptor-mediated endocytosis: its role in alcohol-induced apoptosis. 1833 63

To investigate the effect of taurine on alcoholic liver disease in rats, male Wistar rats were administered alcohol intragastrically for 3 months. The effect of beta-alanine-mediated taurine depletion and taurine administration on the development of alcoholic liver disease was examined. It was found that taurine administration produced lower levels of aspartate aminotransferase and alkaline aminotransferase than that of the untreated group. In addition, the levels of hepatic total protein, glutathione and superoxide dismutase were higher in the taurine treated groups than those in the untreated control or the taurine depleted groups, while hepatic malondialdehyde content exhibited the negative effect. Moreover, the concentrations of hepatic hydroxyproline, serum hyaluronic acid, interleukin-2, interleukin-6, tumor necrosis factor-alpha and laminin were all decreased in the taurine treated groups. The pathological changes showed that the percentage of fatty degeneration and inflammation in the taurine groups were lower than that of the control, taurine depleted and automatic recovery groups. These in vivo findings demonstrate that hepatic disease caused by chronic alcohol consumption can be prevented and cured by administration of taurine.
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PMID:Effect of taurine on alcoholic liver disease in rats. 1850 91

Viral infection of the liver can lead to severe tissue damage when high levels of viral replication and spread in the organ are coupled with strong induction of inflammatory responses. Here we report an unexpected correlation between the expression of a functional X domain encoded by the hepatotropic mouse hepatitis virus strain A59 (MHV-A59), the high-level production of inflammatory cytokines, and the induction of acute viral hepatitis in mice. X-domain (also called macro domain) proteins possess poly-ADP-ribose binding and/or ADP-ribose-1''-phosphatase (ADRP) activity. They are conserved in coronaviruses and in members of the "alpha-like supergroup" of phylogenetically related positive-strand RNA viruses that includes viruses of medical importance, such as rubella virus and hepatitis E virus. By using reverse genetics, we constructed a recombinant murine coronavirus MHV-A59 mutant encoding a single-amino-acid substitution of a strictly conserved residue that is essential for coronaviral ADRP activity. We found that the mutant virus replicated to slightly reduced titers in livers but, strikingly, did not induce liver disease. In vitro, the mutant virus induced only low levels of the inflammatory cytokines tumor necrosis factor alpha and interleukin-6 (IL-6). In vivo, we found that IL-6 production, in particular, was reduced in the spleens and livers of mutant virus-infected mice. Collectively, our data demonstrate that the MHV X domain exacerbates MHV-induced liver pathology, most likely through the induction of excessive inflammatory cytokine expression.
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PMID:Mouse hepatitis virus liver pathology is dependent on ADP-ribose-1''-phosphatase, a viral function conserved in the alpha-like supergroup. 1892 71

To investigate the effect of taurine on alcoholic liver disease in rats, male Wistar rats were administered alcohol intragastrically for 3 months. The effect of beta-alanine-mediated taurine depletion and taurine administration on the development of alcoholic liver disease was examined. It was found that taurine administration produced lower levels of aspartate aminotransferase and alkaline aminotransferase than that of the untreated group. In addition, the levels of hepatic total protein, glutathione and superoxide dismutase were higher in the taurine treated groups than in the untreated control or the taurine depleted group, while hepatic malondialdehyde content exhibited the opposite effect. Moreover, the content of hepatic hydroxyproline, serum hyaluronic acid, interleukin-2, interleukin-6, tumor necrosis factor-alpha and laminin were all decreased in the taurine treated group. The pathological changes showed that the percentage of fatty degeneration and inflammation in the taurine group were less than that of the control, taurine depleted and automatic recovery groups. These in-vivo findings demonstrate that hepatic disease caused by chronic alcohol consumption can be prevented and reversed by administration of taurine.
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PMID:Effect of taurine on alcoholic liver disease in rats. 1923 62

The cytokines are proteins synthetized by lymphoid and monocyte/macrophage system cells in response to a wide variety of infectious stimulus, featuring bacterial endotoxins. These proteins have immunoregulatory effects and have been implicated in inflammation and fibrosis. In this review we refer to the interleukin-1, interleukin-6 and tumor necrosis factor because of their elevated basal levels in acute and chronic hepatopaties and in response to lipopolisacharide mainly in alcoholic liver disease.
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PMID:[Cytokines and the liver]. 1925 29

Nonalcoholic fatty liver disease (NAFLD), comprising its whole spectrum of conditions ranging from simple steatosis to steatohepatitis (nonalcoholic steatohepatitis; NASH) and cirrhosis, is the most frequent liver disease in developed countries and is now regarded as the liver manifestation of the metabolic syndrome. Several studies indicate that NAFLD, especially in its necro-inflammatory form (NASH), is associated with a systemic proinflammatory/prothrombotic state, independently of shared metabolic risk factors. This suggests that NAFLD/NASH is not simply a marker of the proinflammatory/prothrombotic state in the metabolic syndrome but is actively involved in its pathogenesis, possibly through the systemic release of proinflammatory and procoagulant factors from the steatotic liver (C-reactive protein, plasminogen activator inhibitor-1, interleukin-6, fibrinogen, and other proinflammatory cytokines). The clinical impact of NAFLD on the proinflammatory/prothrombotic risk profile deserves particular attention in view of the implications for screening and surveillance strategies in the growing number of patients with NAFLD.
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PMID:Nonalcoholic fatty liver disease as a contributor to hypercoagulation and thrombophilia in the metabolic syndrome. 1945

We investigated haemostatic and inflammatory parameters in patients with cystic fibrosis in an attempt to understand a previous finding of low factor XII levels in this patient population. We selected two groups of patients, adults attending outpatient annual review clinic who were well, chronically inflammed and adult patients with an infective exacerbation requiring antibiotics or admission to hospital, acutely inflammed. We measured known positive acute phase haemostatic factors, fibrinogen and factor VIII. Antithrombin and factor XII were also measured as both these factors have been proposed to be negative acute phase proteins in in-vitro cell models. Interleukin-6 was also measured as the proposed modulator of these factors during inflammation. Activated factor XII was measured to exclude XII activation as a cause of the low XII activity levels. Cystic fibrosis patients admitted to hospital with infective exacerbations, showed significantly more evidence of inflammation than the annual review patients. Fibrinogen and factor VIII were higher and factor XII was lower in these patients. This work suggests that factor XII behaves as a negative acute phase protein with no signs of elevated activated XII levels in either group. This supports similar findings from in-vitro cell culture. This study also shows low antithrombin levels in both patient populations, although there was no statistical difference between groups, which is probably related to their liver disorder.
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PMID:Adult cystic fibrosis patients with and without infective exacerbations and their factor XII levels. 1952 47

The liver plays a central role in the transformation and degradation of endogenous and exogenous chemicals, and in the removal of unwanted cells such as damaged, genetically mutated and virus-infected cells. Because of this function, the liver is susceptible to toxicity caused by the products generated during these natural occurrences. Hepatocyte death is the major feature of liver injury. In response to liver injury, specific intracellular processes are initiated to maintain liver integrity. Inflammatory cytokines including tumor necrosis factor (TNF)alpha and interleukin-6 (IL-6) are key mediators of these processes and activate different cellular response such as proliferation, survival and death. TNFalpha induces specific signaling pathways in hepatocytes that lead to activation of either pro-survival mediators or effectors of cell death. Whereas activation of transcription factor NF-kappaB promotes survival, c-Jun N-terminal kinases (JNKs) and caspases are strategic effectors of cell death in the TNFalpha-mediated signaling pathway. This review summarizes recent advances in the mechanisms of TNFalpha-induced hepatotoxicity and suggests that NF-kappaB plays a protective role against JNK-induced hepatocyte death. Identification of the mechanisms regulating interplay between the NF-kappaB and JNK pathways is required in the search for novel targets for the treatment of liver disease, including hepatitis and hepatocellular carcinoma.
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PMID:Mechanisms of liver disease: cross-talk between the NF-kappaB and JNK pathways. 1964 68

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from benign steatosis to end-stage liver disease. The pathogenesis of non-alcoholic steatohepatitis (NASH) is currently thought to involve a multiple-hit process with the first hit being the accumulation of liver fat which is followed by the development of necroinflammation and fibrosis. There is mounting evidence that cytokines secreted from adipose tissue, namely, adipokines, are implicated in the pathogenesis and progression of NAFLD. In the current review, we explore the role of these adipokines, particularly leptin, adiponectin, resistin, tumor necrosis factor-a, and interleukin-6 in NASH, as elucidated in experimental models and clinical practice. We also comment on their potential use as noninvasive markers for differentiating simple fatty liver from NASH as well as on their potential future therapeutic role in patients with NASH.
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PMID:Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in diagnosis and therapy. 1975 29


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