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

I propose that central nervous system endothelial cells are directly or indirectly responsible for the brain pathology in hepatic encephalopathy, and that this damage to the central nervous system is mediated by specific cytokines and nitric oxide which activate endothelial cells and thereby alter their cell functions. Liver diseases are conditions characterized by high circulating levels of cytokines, namely interleukin-1, interleukin-6 and tumor necrosis factor. Interactions between these cytokines and central nervous system endothelial cells may trigger a cascade of events including enhanced blood-brain barrier permeability, brain edema, astrocyte alterations and gliosis. Cytokine-induced production of nitrogen reactive molecules by endothelial cells themselves may also lead to further cellular damage and neuronal dysfunction. This hypothesis may explain several characteristics of hepatic encephalopathy including reversibility, disease progression and clinical features. It also suggests potential ways of intervention.
 ...
PMID:The role of central nervous system endothelial cell activation in the pathogenesis of hepatic encephalopathy. 867 59

The plasma level of soluble E-selectin (sE) reflects the activation of endothelial cells induced by cytokines such as tumor necrosis factor-alpha and interleukin-1 in vitro. These cytokines are important in the development of coagulation abnormalities in patients with sepsis. We compared the plasma levels of sE in patients with infections suspected of having disseminated intravascular coagulation (DIC) (n = 33) and in patients with underlying disorders other than infections, including solid tumors (n = 28), obstetric disorders (n = 13), hematologic malignancies (n = 13), and liver disease (n = 9), to clarify the involvement of cytokines in the development of coagulation abnormalities in patients with sepsis. Plasma levels of sE in patients with infection were significantly higher than in patients with the other underlying disorders. The plasma level of sE was also significantly higher in patients with infection with DIC (114.6 +/- 77.9 ng/ml, n = 21) than in patients with infection without DIC (54.5 +/- 53.1 ng/ml, n = 12, P < 0.02). There was no significant difference in sE level between patients with the other underlying disorders with and without DIC. The plasma level of sE was significantly correlated with the serum level of FDP(E) in patients with infection. The plasma level of sE was significantly higher in patients with infection with organ failure compared to patients without organ failure. There was no significant difference between patients with the other underlying disorders with and without organ failure. Plasma levels of tumor necrosis factor-alpha and interleukin-6 were detected in only 12.1% and 20.0% of patients with infections, respectively. These observations strongly suggest that plasma levels of sE reflect the activation of endothelial cells induced by cytokines, which may lead to DIC and organ failure in the presence of sepsis. Furthermore, determination of plasma level of sE may be useful for detecting the endothelial activation induced by cytokines in the pathologic conditions of sepsis, even when plasma levels of cytokines cannot be detected.
 ...
PMID:Plasma levels of soluble E-selectin in patients with disseminated intravascular coagulation. 906 1

Interleukin-6 (IL-6) induced activation of Signal Transducer and Activator Transcription Factor 3 (Stat3) is a critical step in liver regeneration. Chronic ethanol consumption is known to increase the plasma concentration of IL-6, yet the ability of the liver to regenerate and the regenerative induction of several IL-6 initiated events are impaired in chronic alcoholic liver disease. We hypothesized that chronic ethanol consumption inhibits IL-6 dependent signal transduction. To test this hypothesis, the effect of ethanol on the Stat3 signal transduction pathway was studied in the adult rat liver. In vitro treatment of freshly isolated normal adult rat hepatocytes with 50-100 mM ethanol for 30 min blocked IL-6-induced Stat3 activation. Long-term ethanol intake in vivo significantly attenuated the activation of Stat3 induced either in vivo by partial hepatectomy or in vitro by IL-6. In contrast, short-term ethanol consumption enhanced the regenerative induction of Stat3 but inhibited IL-6 induced Stat3 activation. These data suggest that the inhibition of liver regeneration by chronic ethanol consumption is, at least in part, mediated by modulating the activation of Stat3.
 ...
PMID:Effects of short and long term ethanol on the activation of signal transducer and activator transcription factor 3 in normal and regenerating liver. 936 25

The role of T-cell activation in alcoholic liver disease was investigated in rats fed alcohol and subsequently exposed to concanavalin A (Con A). Following Con A injection (20 mg/kg body weight), greater increases in liver-to-body weight ratio and ALT levels were observed at 12 and 24 hr in rats fed ethanol, compared with control rats fed sucrose. Furthermore, increases in serum interleukin-6 and tumor necrosis factor-alpha levels were noted in ethanol-fed rats, with maximal levels detected at 4 hr declining thereafter, but remaining above control levels at 24 hr. Analysis of T-cell subpopulations showed an increased percentage of CD4+, CD5+, and CD8+ T cells in blood from all groups, but not in liver perfusate. In contrast, a significant increase in the percentage of activated CD25+ T cells was detected in both blood and liver perfusate from rats fed ethanol even 24 hr after Con A injection. When CD4+ and CD8+ T cells from liver perfusate were cultured in the absence or presence of Con A, an increase in interleukin-6 and tumor necrosis factor-alpha production in supernatants was observed in ethanol-fed rats. In cultures stimulated with Con A, a 2- to 8-fold increase in cytokine production was detected, with intrahepatic CD4+ T cells being the major source. Immunohistological analysis revealed infiltration of CD4+ T cells around portal vein and central vein areas associated with fatty liver and severe hepatic necrosis. The results suggest that alcohol consumption induced a dysregulated T-cell population that mediated hepatic necrosis following polyclonal activation with Con A.
 ...
PMID:Altered T-lymphocyte responsiveness to polyclonal cell activators is responsible for liver cell necrosis in alcohol-fed rats. 962 56

The aims of the present study were to examine (1) the inflammatory response system (IRS), through measurements of serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sgp130 (the soluble form of the IL-6 transducer signal protein), CC16 (Clara Cell protein; an endogenous anti-cytokine), IL-1R antagonist (IL-1RA), IL-8 and sCD14; and (2) the availability of plasma total tryptophan to the brain in chronic alcoholic patients without apparent liver disease (AWLD). Detoxified AWLD patients had significantly lower plasma tryptophan and serum CC16 and significantly higher serum IL-1RA and IL-8 concentrations than normal volunteers. There were significant correlations between the availability of tryptophan to the brain and serum IL-6, IL-8 and IL-1RA (all negative) and CC16 (positive). The results suggest that (1) there is, in detoxified AWLD patients, an activation of the monocytic arm of cell-mediated immunity and a lowered anti-inflammatory capacity of the serum; and that (2) lower availability of plasma tryptophan to the brain in detoxified AWLD patients is related to activation of the IRS. Lower CC16 may be one factor predisposing chronic alcoholic patients toward infectious disorders.
 ...
PMID:Serotonin-immune interactions in detoxified chronic alcoholic patients without apparent liver disease: activation of the inflammatory response system and lower plasma total tryptophan. 965 19

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.
 ...
PMID:Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. 966 31

Increased levels of hepatic and serum tumor necrosis factor (TNF) have been documented in animal models of alcoholic liver disease and in human alcoholic liver disease. This dysregulated TNF metabolism has been postulated to play a role in many of the metabolic complications and the liver injury of alcoholic liver disease. One potential therapy for alcoholic liver disease may be agents that downregulate TNF production or block TNF activity. Indeed, agents such as prostaglandins and glucocorticoids (both inhibit TNF production) have been used in both human liver disease and experimental models of liver injury, and anti-TNF antibody has recently been shown to attenuate the hepatotoxicity in an animal model of alcoholic-related liver disease. In this study, we demonstrate that a simple ex vivo system can be used to initially assess potential efficacy of anticytokine agents when administered to humans. Both prednisone and a prostaglandin analog were effective in downregulating TNF and interleukin-8 production. The liver is normally resistant to TNF cytotoxicity. Sensitivity to TNF cytotoxicity is thought to occur when there is inadequate production of hepatic protective factors. In this study, we showed that, when patients with acute alcoholic hepatitis were matched with trauma patients for serum levels of interleukin-6, they had similar depressions in the negative acute phase protein, albumin, but markedly different increases in the major acute phase protein, C reactive protein. Patients with alcoholic hepatitis had a very blunted response. We also showed that inhibiting activation of the redox sensitive transcription factor NFkappaB sensitizes to TNF-induced hepatocyte death in vitro. This transcription factor is important for the production of both cytokines and many acute phase protective factors. Several hepatic protective factors are induced by TNF. One possible mechanism for liver injury in alcoholic hepatitis may be inadequate generation of hepatic protective factors. Our future understanding of mechanisms of alcoholic liver disease will involve understanding the balance between noxious and protective factors in the liver, and this should lead to rational therapy for this disease process.
 ...
PMID:Tumor necrosis factor and alcoholic liver disease. 972 45

This study examines i) the activity of serum prolyl endopeptidase (PEP) and dipeptidlyl peptidase IV (DPP IV) in detoxified alcohol-dependent patients without liver disease versus normal controls, and ii) the relationships between serum DPP IV and PEP activity and the production of cytokines or cytokine receptors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interferon-y (IFN-y), IL-1 receptor antagonist (IL-1RA), and IL-10, and granulocyte-macrophage colony stimulatory factor (GM-CSF). Alcohol-dependent patients had significantly lower serum PEP and DPP IV activity than normal controls. We found that 58.3% and 50.0% of the alcohol-dependent patients, respectively, had PEP and DPP IV activities, which were lower than the mean control values minus 2 SD. There were significant inverse correlations between lowered serum DPP IV and PEP activity and the increased production of IL-6, INF-gamma, IL-IRA, IL-10, and GM-CSF. These results show that lower serum DPP IV and PEP activity may be related to the pathophysiology of alcohol dependence.
 ...
PMID:Lower activity of serum peptidases in abstinent alcohol-dependent patients. 989 30

Hepatocyte growth factor (HGF), interleukin-6 (IL-6), and C-reactive protein (CRP) are acute-phase reactants that are usually present at high concentrations in the serum of patients with liver disease. However, the origin of these high serum concentrations is not completely understood, and whether hepatocellular carcinoma (HCC) tissue is a contributing factor is a controversial issue. The purpose of this study was to investigate the profiles of these three proteins in patients with HCC before and after tumor resection, and to study factors that might affect the serum concentrations of these proteins. A retrospective cohort study was performed in 34 consecutive patients who underwent HCC resection at the National Taiwan University Hospital. Blood samples were collected before surgery and on days 1, 3, 5, 7, and 14 postoperatively for serum concentration determinations of these three proteins. Twenty-three patients admitted for health examinations were enrolled as normal controls. Multiple regression analysis was conducted to evaluate the correlations between the pre- and postoperative cytokine concentrations and various clinical parameters. Compared with normal controls, the HCC patients had a significantly higher preoperative concentration of HGF (1,472 +/- 73 vs 948 +/- 54 ng/mL, p < 0.001) and IL-6 (44.1 +/- 6.9 vs 8.1 +/- 3.2 pg/mL, p = 0.012). These concentrations peaked on the first postoperative day and then declined to preoperative values on the fifth postoperative day. The CRP concentration was also higher in HCC patients (0.88 +/- 0.22 vs 0.21 +/- 0.06 mg/dL, p = 0.222), but the difference was not statistically significant. However, the CRP concentration did not return to the preoperative value within 2 weeks postoperatively. Preoperatively, HGF and CRP concentrations were positively affected by larger tumor size, and IL-6 concentration was negatively affected by hepatitis B surface antigen positivity and a higher indocyanine green (ICG) retention rate. In summary, the serum concentrations of HGF and IL-6 were significantly higher in HCC patients than in normal controls. The serum concentrations of HGF, IL-6, and CRP rose dramatically after HCC resection. The concentrations of these proteins were affected by different clinical parameters. We proved indirectly that high serum concentrations of HGF, IL-6, and CRP in patients with HCC do not result primarily from synthesis by the tumor cells. Whether the preoperative concentrations of these proteins correlate with the clinical outcome needs further follow-up.
 ...
PMID:Secretion of acute-phase proteins before and after hepatocellular carcinoma resection. 1008 62

Recently, it was reported that there may be an activation of the inflammatory response system in detoxified alcohol-dependent patients without apparent liver disease (AWLD). The aims of the present study were to examine serum zinc (Zn) concentrations, total serum protein (TSP) and patterns obtained in the electrophoretically separated protein fractions in relation to serum interleukin-6 (IL-6) and IL-8 concentrations in detoxified AWLD patients. Zn, TSP, SP electrophoresis, and serum IL-6 and IL-8 concentrations were determined in detoxified AWLD patients and age-matched healthy volunteers. Serum Zn, TSP and the serum concentrations of albumin (Alb) and the beta fraction were significantly lower in detoxified AWLD patients than in healthy volunteers. The percentage of the alpha2 fraction was significantly higher in detoxified AWLD patients. Lower serum Zn in detoxified AWLD patients was attributable to lowered serum Alb. Lower serum Alb was significantly and negatively correlated to increased serum IL-8. The percentage of the alpha1 and alpha2 fractions were significantly and positively related to serum IL-6 and IL-8. The results show that there is an in vivo activation of the inflammatory response system in detoxified AWLD patients and that lower serum Zn may be causally related to lower serum Alb.
 ...
PMID:Lower serum zinc in relation to serum albumin and proinflammatory cytokines in detoxified alcohol-dependent patients without apparent liver disease. 1008 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>