UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incidence of bacterial infections in hospitalised patients with liver disease is high. Due to a liver dysfunction immune reactivity is significantly impaired and bacterial infections are more frequent. Also incidence of nosocomial infections is higher in patients with liver disease compared to patients hospitalised for other conditions. To make a differential diagnosis of infectious and non-infectious aetiology of an inflammation is very difficult. Characteristic laboratory tests for bacterial infection include test of a number of leucocytes in peripheral blood, differential count of leucocytes, erythrocyte sedimentation, procalcitonin, C-reactive protein, tumor necrosis factor alpha, interleukin-1, interleukin-6, interleukin-8, and complement fragment C3a. Clinically the most significant are C-reactive protein test and procalcitonin test. Procalcitonin is a protein, a calcitonin precursor, which is in healthy individuals produced by cells of thyroid gland. A half-life of procalcitonin in serum is 20-24 hours which makes it suitable for daily monitoring and enables to control a course of treatment and to distinguish bacterial infection from other types of inflammations. Procalcitonin levels rise in bacterial, parasite, and yeast infections. Elevated procalcitonin levels appear only in inflammations of an infectious etiology with systemic signs. In patients with liver cirrhosis bacterial infections are more frequent. They usually include spontaneous bacterial peritonitis, infection of the respiratory system, urinary infections, and bacteremia. A timely proof of a bacterial infection and an appropriate and effective antibiotic therapy lead to an improvement of the general state of a patient and to his/her better prognosis. Procalcitonin determination is appropriate for diagnosing infections and control of treatment.
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PMID:[Procalcitonin as an indicator of infection in patients with liver cirrhosis]. 1507 92

Patients with cirrhosis and ascites show systemic and splanchnic arterial vasodilation, which causes a reduction in effective arterial blood volume and the activation of hormonal anti-natriuretic systems. Renal impairment is the most important predictor of hospital mortality in cirrhotic patients with SBP. In patients with SBP, the inflammatory response to the infection (TNF-alpha, IL-6) may be an important mechanism of renal dysfunction. Ascitic-fluid NO metabolites are related independently to the development of renal impairment. Treatment of SBP with intravenous albumin in addition to cefotaxime prevents renal impairment and reduces mortality in comparison with treatment with cefotaxime alone. As soon as ascites develops, liver transplantation should be considered in eligible patients, especially when local mean waiting times exceed life expectancy. Nitric oxide (NO), tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) have been implicated in the pathogenesis of circulatory alterations observed in cirrhotic patients with ascites. Kidney failure is one of the main factors associated with mortality in patients with end-stage liver disease developing complications, particularly severe infections and variceal haemorrhage. Renal impairment occurs in patients with the highest concentration of cytokines in plasma and ascitic fluid and is associated with marked activation of the renin-angiotensin system. In patients with spontaneous bacterial peritonitis (SBP), serum and ascitic fluid levels of NO metabolites (nitrites and nitrates) were higher than those of patients with sterile ascites, and renal impairment is considered to be caused by a decrease in effective arterial blood volume as a result of the infection. The administration of albumin prevents deterioration of renal function and reduces mortality in these patients. However, SBP and renal dysfunction are late complications in the course of liver cirrhosis. As soon as ascites develops, liver transplantation should be considered in eligible patients, especially when local mean waiting times exceed life expectancy. A better knowledge of metabolic disorders associated with the early stage of cirrhosis is essential for the development of optimal therapeutic strategies for the prophylaxis and treatment of portal hypertension and its complications.
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PMID:Nitric oxide and renal function in cirrhotic patients with ascites: from physiopathology to practice. 1516 58

Serum interleukin-6 concentrations in patients with alcoholic liver disease Pathogenesis of alcoholic liver disease (ALD) is not well defined, but immune mediated hepatic injury is thought to be important. The main aim of this study was estimation of serum concentrations of IL-6 in patients with chronic alcoholic liver disease and determination of correlations between IL-6 serum concentration and occurrence of clinical manifestations, biochemical parameters and a stage of ALD. 85 patients with the diagnosis of chronic ALD and 35 healthy subjects (mached for age and sex) were enrolled into the study. Serum concentration of IL-6 was measured with ELISA. Serum IL-6 concentrations were markedly elevated in the all analyzed groups of patients with ALD when compared with healthy controls. When compared in groups, patients with alcoholic cirrhosis and chronic alcoholic hepatitis had the highest and patients with fatty liver had the lowest serum IL-6 concentrations. In addition, IL-6 concentrations were higher in patients with hepatic encephalopathy than in those without liver failure. Furthermore, we found statistically significant correlation between serum IL-6 and albumin concentrations. High IL-6 concentrations were associated with high mortality in patients with ALD. These findings suggest that IL-6 is an important immunological factor associated with alcoholic liver disease.
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PMID:[Serum interleukin-6 concentrations in patients with alcoholic liver disease]. 1562 53

Alcoholic liver disease is a major cause of illness and death in the United States. In the initial stages of the disease, fat accumulation in hepatocytes leads to the development of fatty liver (steatosis), which is a reversible condition. If alcohol consumption is continued, steatosis may progress to hepatitis and fibrosis, which may lead to liver cirrhosis. Alcoholic fatty liver has long been considered benign; however, increasing evidence supports the idea that it is a pathologic condition. Blunting of the accumulation of fat within the liver during alcohol consumption may block or delay the progression of fatty liver to hepatitis and fibrosis. To achieve this goal, it is important to understand the underlying biochemical and molecular mechanisms by which chronic alcohol consumption leads to fat accumulation in the liver and fatty liver progresses to hepatitis and fibrosis. In addition to alcohol consumption, dietary fatty acids and obesity have been shown to affect the degree of fat accumulation within the liver. Again, it is important to know how these factors modulate the progression of alcoholic liver disease. The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on "Role of Fatty Liver, Dietary Fatty Acid Supplements, and Obesity in the Progression of Alcoholic Liver Disease" in Bethesda, Maryland, USA, October 2003. The following is a summary of the symposium. Alcoholic fatty liver is a pathologic condition that may predispose the liver to further injury (hepatitis and fibrosis) by cytochrome P450 2E1 induction, free radical generation, lipid peroxidation, nuclear factor-kappa B activation, and increased transcription of proinflammatory mediators, including tumor necrosis factor-alpha. Increased acetaldehyde production and lipopolysaccharide-induced Kupffer cell activation may further exacerbate liver injury. Acetaldehyde may promote hepatic fat accumulation by impairing the ability of peroxisome proliferator-activated receptor alpha to bind DNA, and by increasing the synthesis of sterol regulatory binding protein-1. Unsaturated fatty acids (corn oil, fish oil) exacerbate alcoholic liver injury by accentuating oxidative stress, whereas saturated fatty acids are protective. Polyenylphosphatidylcholine may prevent liver injury by down-regulating cytochrome P450 2E1 activity, attenuating oxidative stress, reducing the number of activated hepatic stellate cells, and up-regulating collagenase activity. Nonalcoholic steatohepatitis may develop through several mechanisms, such as oxidative stress, mitochondrial dysfunction and associated impaired fat metabolism, dysregulated cytokine metabolism, insulin resistance, and altered methionine/S-adenosylmethionine/homocysteine metabolism. Obesity (adipose tissue) may contribute to the development of alcoholic liver disease by generating free radicals, increasing tumor necrosis factor-alpha production, inducing insulin resistance, and producing fibrogenic agents, such as angiotensin II, norepinephrine, neuropeptide Y, and leptin. Finally, alcoholic fatty liver transplant failure may be linked to oxidative stress. In vitro treatment of fatty livers with interleukin-6 may render allografts safer for clinical transplantation.
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PMID:Role of fatty liver, dietary fatty acid supplements, and obesity in the progression of alcoholic liver disease: introduction and summary of the symposium. 1567 Jun 59

Donor organ shortage significantly hinders orthotopic liver transplantation therapy, the only effective treatment for chronic end-stage liver disease and acute liver failure. Further complicating this matter is the prevalence of steatosis in 13% to 50% of donor livers obtained from obese and alcoholic individuals. When transplanted, these livers are associated with primary nonfunction and an elevated risk of dysfunction. New therapeutic approaches to render marginal fatty livers worthy for clinical transplantation are actively being sought. Study findings obtained from my group show that in vitro treatment with interleukin-6 (IL-6) dramatically reduces mortality, liver injury, and necrapoptosis in steatotic Zucker rat liver isografts. Findings of additional studies indicate that IL-6 induces hepatoprotection of steatotic liver isografts by preventing sinusoidal endothelial cell damage and, consequently, the amelioration of hepatic microcirculation, and by protecting against hepatocyte death, which is likely mediated through activation of signal transducer and activator of transcription 3/Bcl-x(L). Finally, in vitro IL-6 treatment also prevents mortality associated with alcoholic fatty liver transplants. Relative to the protective effect of IL-6 on steatotic Zucker rat liver, IL-6 is less effective in alcoholic fatty livers, which may be due to the inhibitory effects of ethanol on IL-6 activation of signal transducer and activator of transcription 3 in hepatocytes and sinusoidal endothelial cells. Collectively, these results support the assertion that in vitro IL-6 treatment of steatotic livers may render allografts usable for clinical transplantation, thereby decreasing the gap between the short supply of cadaver liver allografts and high demands for replacement livers. Higher concentrations of IL-6 may be required to protect against alcoholic fatty liver isograft injury because alcohol inhibits IL-6 signaling in the liver.
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PMID:Therapeutic potential of interleukin-6 in preventing obesity- and alcohol-associated fatty liver transplant failure. 1567 Jun 67

The aim of this study was to evaluate a possible relationship between lymphomonocyte expression of heat shock proteins (HSP) 60/27 and plasma levels of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) and markers of antioxidant/oxidative status [glutathione (GSH), alpha glutathione-S-transferase activity (alpha GST), malonyldialdeyde (MDA), 4-hydroxinonenal (4-HNE), and S-nitrosothiols (S-NO)] in patients with chronic liver diseases. Entered into the study were 47 subjects: 10 healthy controls, 16 patients with HCV-related chronic hepatitis (CH), and 16 patients with HCV-related and 5 with alcohol-related liver cirrhosis (10 Child A and 11 Child B+C). HSP60 was clearly expressed only in 5% of patients and lowly in the control group. HSP27 was clearly expressed in 46.7% of CH and 71.4% of cirrhotic patients but was lowly present in healthy subjects. A significant difference was found between patients with a low expression of HSP27 (negative patients) and those with a high HSP27 expression (positive patients) of plasma levels both of antioxidants (GSH, p < 0.05), and of markers of enhanced production of free radicals and cytokines (alpha GST, TNF-alpha and IL-6, p < 0.05; MDA, 4-HNE and S-NO, p < 0.01) as well as for alcohol use and degree of liver impairment. The present data are the first showing that, particularly in conditions of enhanced oxidative stress, lymphomonocytes from liver disease patients present an increased expression of HSP27.
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PMID:Heat shock protein 27 expression in patients with chronic liver damage. 1596 49

Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however, the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression of ethanol-induced oxidative stress and mitochondrial dysfunction. To test this hypothesis, we examined the effects of IL-6 on ethanol-induced oxidative stress, mitochondrial injury, and energy depletion in the livers of IL-6 (-/-) mice and hepatocytes from ethanol-fed rats. Ethanol consumption leads to stronger induction of malondialdehyde (MDA) in IL-6 (-/-) mice compared to wild-type control mice, which can be corrected by administration of IL-6. In vitro, IL-6 treatment prevents ethanol-mediated induction of reactive oxygen species (ROS), MDA, mitochondrial permeability transition (MPT), and ethanol-mediated depletion of adenosine triphosphate (ATP) in hepatocytes from ethanol-fed rats. Administration of IL-6 in vivo also reverses ethanol-induced MDA and ATP depletion in hepatocytes. Finally, IL-6 treatment induces metallothionein protein expression, but not superoxide dismutase and glutathione peroxidase in cultured hepatocytes. In conclusion, IL-6 protects against ethanol-induced oxidative stress and mitochondrial dysfunction in hepatocytes via induction of metallothionein protein expression, which may account for the protective role of IL-6 in alcoholic liver disease.
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PMID:IL-6-deficient mice are susceptible to ethanol-induced hepatic steatosis: IL-6 protects against ethanol-induced oxidative stress and mitochondrial permeability transition in the liver. 1621 69

In animals, the bone marrow (BM) is a source of liver-repopulating cells with therapeutic potential in case of tissue damage. However, the early response of human BM-derived stem cells (SC) to liver injury is still unknown. Here, we studied 24 patients undergoing orthotopic liver transplantation (OLT) for end-stage liver disease or hepatocellularcarcinoma, and 13 patients submitted to liver resection. The concentration of circulating BM-derived SC was determined by phenotypic analysis and clonogenic assays. Moreover, we assessed the serum level of inflammatory and tissue-specific cytokines. Reverse transcriptase-polymerase chain reaction and fluorescence-in situ hybridization were also used to characterize mobilized SC. At baseline, patients showed a significant lower concentration of circulating CD133(+), CD34(+) SC and clonogenic progenitors (colony-forming unit cells) than healthy controls. However, the time-course evaluation of peripheral blood cells after OLT demonstrated the significant early mobilization of multiple subsets of hematopoietic and endothelial stem/progenitor cells. Cytogenetic and molecular analyses of CD34(+) cells showed the host origin of mobilized SC and the expression of transcripts for GATA-4, cytokeratin 19, and alpha-fetoprotein hepatocyte markers. In contrast with OLT, only total circulating CD34(+) cells significantly increased after liver resection. Mobilization of BM cells after OLT or liver surgery was associated with increased serum levels of granulocyte-colony stimulating factor, interleukin-6, stem cell factor, hepatocyte growth factor, and vascular endothelial growth factor. In summary, we demonstrate that tissue damage after OLT and liver resection induces increased serum levels of multiple cytokines but only ischemia/reperfusion injury associated with OLT results in the remarkable mobilization of BM stem/progenitor cells.
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PMID:Mobilization of bone marrow-derived hematopoietic and endothelial stem cells after orthotopic liver transplantation and liver resection. 1693 69

Alcohol abuse is a major cause of liver cirrhosis as well as chronic liver disease. The aim of the present study was to investigate the possible correlation, between liver dysfunction biological markers and vitamin B12, with interleukin-6, in the serum of alcohol-dependent individuals without liver disease (AWLD). In a sample of 43 alcohol abusing/dependent subjects (33 males and 10 females) treated on an inpatient basis according to a standard detoxification protocol, the serum activities of the hepatic enzymes (ASAT, ALAT, gamma-GT), as well as the concentration of B12 and IL-6, were determined on admission. A strong positive correlation has been observed between IL-6 and B12, ASAT, ALAT, and gamma-GT at the beginning of the detoxification period. The results confirmed that in alcohol-dependent individuals, the median serum concentration of IL-6, before the beginning of the treatment, had a significant positive correlation with the liver dysfunction biological markers and B12. In conclusion, IL-6 might be used as an additional diagnostic marker for the degree of liver dysfunction in alcohol dependent individuals.
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PMID:Vitamin B12 and hepatic enzyme serum levels correlate with interleukin-6 in alcohol-dependent individuals without liver disease. 1744 94

In this study, we examined the relative contribution of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO), two major proinflammatory pathways up-regulated in liver disease, to the progression of hepatic inflammation and fibrosis. Separate administration of 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-236), a selective COX-2 inhibitor, and CJ-13,610, a 5-LO inhibitor, to carbon tetrachloride-treated mice significantly reduced fibrosis as revealed by the analysis of Sirius Red-stained liver sections without affecting necroinflammation. Conversely, combined administration of SC-236 and 4-[3-[4-(2-methylimidazol-1-yl)-phenylthio]]phenyl-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide (CJ-13,610) reduced both necroinflammation and fibrosis. These findings were confirmed in 5-LO-deficient mice receiving SC-236, which also showed reduced hepatic monocyte chemoattractant protein 1 expression. Interestingly, SC-236 and CJ-13,610 significantly increased the number of nonparenchymal liver cells with apoptotic nuclei (terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive). Additional pharmacological profiling of SC-236 and CJ-13,610 was performed in macrophages, the primary hepatic inflammatory cell type. In these cells, SC-236 inhibited prostaglandin (PG) E2 formation in a concentration-dependent manner, whereas CJ-13,610 blocked leukotriene B4 biosynthesis. Of note, the simultaneous addition of SC-236 and CJ-13,610 resulted in a higher inhibitory profile on PGE2 biosynthesis than the dual COX/5-LO inhibitor licofelone. These drugs differentially regulated interleukin-6 mRNA expression in macrophages. Taken together, these findings indicate that both COX-2 and 5-LO pathways are contributing factors to hepatic inflammation and fibrosis and that these two pathways of the arachidonic acid cascade represent potential targets for therapy.
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PMID:Comparative protection against liver inflammation and fibrosis by a selective cyclooxygenase-2 inhibitor and a nonredox-type 5-lipoxygenase inhibitor. 1776 77

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