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

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

Phospholipase A(2) IIA (PLA(2)IIA), which plays a crucial role in arachidonic acid metabolism and in inflammation, is upregulated under various pathological conditions, including in the gallbladder and gallbladder bile from patients with multiple cholesterol gallstones, in the liver and kidney of rats with cirrhosis, as well as in the colonic tissue of animals treated with a chemical carcinogen. The administration of ursodeoxycholic acid (UDCA) partially attenuated the PLA(2)IIA expression level in these different models. The aim of this study was to investigate the modulatory effect of UDCA on the PLA(2)IIA expression level at the cellular level. The HepG2 cells were selected to investigate the direct inhibitory effect of UDCA on PLA(2)IIA expression level. The proinflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) -induced PLA(2)IIA expression in HepG2 cells was partially inhibited by the presence of UDCA in a dose-dependent fashion. The effect of UDCA on proinflammatory cytokines-induced PLA(2)IIA expression occurred at the transcriptional level. In addition, among the bile acids tested, this inhibitory effect was UDCA-specific. In conclusion, this study supports the possible alteration of arachidonic acid metabolism and PLA(2)IIA expression level, in particular, as the protective action of UDCA in patients with chronic liver disease.
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PMID:Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells. 1579 50

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) is an important mediator of liver regeneration and repair that is also elevated in chronic liver diseases, including fatty liver of obesity and cirrhosis. IL-6 has been reported both to delay and accelerate liver regeneration. We examined the effects on liver injury and regeneration of a continuous administration of exogenous IL-6 to mice by injection of an IL-6-expressing CHO-cell line in athymic nude mice and by osmotic mini-pump delivery of recombinant murine IL-6. Short-term IL-6 administration (1-2 days) accelerated early recovery of liver mass, whereas more long-term administration (5-7 days) markedly impaired liver regeneration. Similarly, short-term IL-6 treatment increased hepatic resistance to the lethal effects of the Fas agonist Jo-2, but on more prolonged IL-6 exposure the Jo-2 resistance vanished. IL-6 administration initially induced expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, correlating with protection against Fas-mediated cell death. More prolonged IL-6 administration, however, resulted in marked induction of the pro-apoptotic protein Bax. This result coincided with increased activation of the type II or intrinsic, mitochondrial path to cell death, manifested by increased caspase-9 activation and increased cytochrome c release after Jo-2 exposure. These data demonstrate that IL-6 can function acutely to improve hepatic regeneration and repair, but that more chronic exposure not only abolishes the protective effects of IL-6, but actually sensitizes the liver to injury and death. In conclusion, elevated IL-6 in certain chronic liver diseases contributes to an increased likelihood of liver failure after injury.
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PMID:Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair. 1649 6

Chronic bile duct ligation (BDL) is a useful model of cirrhosis. However, its parallel plasma and liver changes in levels of cytokines and nitric oxide (NO), involved in liver damage, remain unknown. The aims of this work were to quantify both the plasma and hepatic levels of five cytokines and NO in cirrhotic rats, 28 days after bile BDL, and to analyze their relationship with liver damage markers. One group of male Wistar rats was bile duct ligated and another group was sham operated, both groups were sacrificed 28 days after BDL. Plasma and liver cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, -1beta, -10 (IL-6, -1beta, -10) and interferon-gamma (IFN-gamma), were measured by ELISA. Plasma and hepatic NO was determined as NO(2)(-)+NO(3)(-) by an enzymatic method. Alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase and bilirubins were determined in plasma. Collagen, lipid peroxidation and glycogen were quantified in liver. Two histopathological staining techniques were performed. BDL-induced cirrhosis was corroborated by the elevated liver damage markers and histopathological analysis. Chronic BDL significantly increased (P<0.05) most of plasma and hepatic cytokine levels and diminished the hepatic IFN-gamma amount. NO was increased in both tissues, but such change was only significant in plasma. Biliary cirrhosis produces interesting changes in plasma and hepatic levels of cytokines and NO. This finding in chronic BDL model in rats has not been previously described in both tissues for such cytokines and NO. Cytokines and NO imbalance favor establishment and perpetuation of cirrhosis.
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PMID:Chronic bile duct obstruction induces changes in plasma and hepatic levels of cytokines and nitric oxide in the rat. 1661 7

Interleukin-6 (IL-6) is an important cytokine in liver regeneration, and elevated levels of IL-6 have been demonstrated in patients with chronic liver diseases (CLD). Many biological effects of IL-6 depend on naturally occurring soluble IL-6 receptors. In the present study we measured the concentrations of IL-6 and its soluble receptors in the sera of patients with CLD related to hepatitis C virus (HCV) infection. We studied 77 patients with varying degrees of HCV-related CLD. Serum levels of IL-6 and its soluble receptors (sIL-6R, sgp130) were measured by enzyme-linked immunosorbent assay. Serum IL-6 and sIL-6R were elevated in patients with CLD compared with healthy subjects. Serum levels of sgp130 did not differ between patients with chronic hepatitis and healthy subjects. However, in patients with liver cirrhosis, sgp130 was significantly elevated and was positively correlated with total bilirubin and negatively correlated with cholinesterase and prothrombin time. Our study demonstrated that in patients with HCV-related CLD, serum IL-6 and its soluble receptor levels are correlated with both liver function impairment and the degree of liver fibrosis. These observations suggest that the balance of IL-6 and its soluble receptors may correspond to the state of liver damage in patients with CLD.
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PMID:Serum levels of interleukin-6 and its soluble receptors in patients with hepatitis C virus infection. 1669 22

Bacterial DNA (bactDNA) is present in blood and ascitic fluid (AF) in a third of patients with cirrhosis and ascites, but whether this phenomenon represents episodes of bacterial translocation (BT), strictly considered when culture of mesenteric lymph nodes (MLNs) are positive, remains unknown. This study assessed the relationship between bactDNA detection in biological fluids and MLNs and went on to investigate the local and systemic inflammatory status according to its presence. Cirrhosis was induced in rats by ingestion of CCL4. A subgroup of five animals with cirrhosis received norfloxacin (5 mg/kg/day) for 7 days. MLNs and ascitic and pleural fluids were collected at laparotomy and cultured; samples were collected for identification of bactDNA and measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO). BactDNA was detected in MLNs in 12 of 19 animals (63.1%), corresponding in seven cases to culture-positive MLNs, and in five to culture-negative MLNs. BactDNA was detected in biological fluids in 11 of 19 animals (57.9%), and in all cases the same bacteria spp. detected in samples was present in MLNs. BactDNA was not detected in any biological sample from animals receiving norfloxacin. Tumor necrosis factor alpha (TNF-alpha), IL-6, and NO were similar in culture-positive and culture-negative/bactDNA-positive samples, and significantly higher than those observed in animals with culture-negative/bactDNA-negative MLNs, animals with cirrhosis that were receiving norfloxacin, and controls. In conclusion, the presence of bactDNA in biological fluids in rats with cirrhosis constitutes a marker of BT, and it is associated with a marked inflammatory response, independent of the result of the culture.
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PMID:The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation. 1694 89

Binge ethanol (EtOH) consumption suppresses inflammatory responses and resistance to infection, but paradoxically it is associated with increased levels of acute phase proteins (which are indicators of inflammation) and an increased risk of inflammation-mediated pathologies such as cardiovascular disease and cirrhosis of the liver. The latter effect may be mediated by increased translocation of bacteria leading to activation of toll-like receptor 4 (TLR4). In this study, the dose-response and time course of the effects of EtOH alone or EtOH in conjunction with a TLR4 agonist (lipopolysaccharide [LPS]) were evaluated in mice. EtOH alone at a dosage of 6 g/kg induced an acute phase response (as indicated by enzyme-linked immunosorbent assay for serum amyloid A and serum amyloid P) that was maximal 24 h after dosing. Lower dosages of EtOH did not have this effect but did suppress the acute phase response to LPS and the production of interleukin-6 up to 3 h after dosing. EtOH at 6 g/kg did not induce an acute phase response in C3H/HeJ (TLR4 mutant) mice, indicating that this response is mediated through TLR4. These results provide a resolution for the apparently paradoxical pro- and anti-inflammatory actions of EtOH with regard to acute phase responses.
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PMID:An explanation for the paradoxical induction and suppression of an acute phase response by ethanol. 1713 63

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