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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By two exemplary clinical situations--acute viral hepatitis, acute-phase reaction of the liver--the significance of basic research for the understanding of clinical phenomena and for the development of new diagnostic and therapeutic procedures is demonstrated. The very different phenomena following infection with the hepatitis-B-virus can be explained by the variation in the interactions of virus and liver cell, by the immune reaction of the host, and by mutants of the virus. The reaction of the liver to an extrahepatic infection is mediated by interleukin-6, and characterized by an alteration in protein metabolism. The synthesis of acute-phase proteins is increased. The proteins confine the local injury and establish the homeostasis of the organism.
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PMID:[Hepatology. New research results in its significance for the understanding of liver diseases]. 171 53

The potential effects of cytokines on hepatocellular transport functions remain undefined. Interleukin-6 (IL-6) is a cytokine that is produced in sepsis, hepatitis, and other inflammatory conditions often associated with cholestasis. Using cultured rat hepatocytes, we have investigated the effects of IL-6 on hepatocellular bile salt uptake. Because hepatocyte Na(+)-K(+)-adenosinetriphosphatase (ATPase) produces the electrochemical gradient that drives sodium-dependent bile salt contransport, we also examined the effects of IL-6 on Na(+)-K(+)-ATPase activity. Hepatocytes cultured for 20 h in media containing IL-6 exhibited a dose-dependent noncompetitive inhibition of [3H]taurocholate uptake, which was maximal at an IL-6 dose of 100 U/ml. IL-6 treatment had no effect on hepatocyte sodium-independent taurocholate uptake. Northern blotting of RNA from cultured hepatocytes revealed that IL-6 had no effect on steady-state RNA levels of the Na(+)-taurocholate transporter (Ntcp). Hepatocytes incubated with IL-6 for 20 h, however, exhibited a 55% decrease in hepatocyte Na(+)-K(+)-ATPase activity. This effect also was dose dependent, with maximal inhibition occurring at an IL-6 dose of 100 U/ml. Similar treatment with IL-6 did not influence hepatocyte Mg(2+)-ATPase activity. The inhibition of Na(+)-K(+)-ATPase activity induced by IL-6 provides a putative mechanism for the observed inhibition of sodium-dependent taurocholate uptake. Since modulation of bile salt transport and Na(+)-K(+)-ATPase activity occurred at IL-6 concentrations comparable to the serum levels observed in patients with severe inflammatory states, these findings have potential pathophysiological relevance for the cholestasis of sepsis and other inflammatory disorders.
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PMID:Interleukin-6 inhibits hepatocyte taurocholate uptake and sodium-potassium-adenosinetriphosphatase activity. 781 Jun 56

Circulating levels of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in 13 children with autoimmune hepatitis (AIH) (seven with type 1 and six with type 2). In untreated children with type 1 AIH, TNF-alpha, IL-6, and IL-8 levels were elevated when compared to those of healthy controls (p < 0.005, p < 0.02, p = 0.06, respectively), whereas in children with type 2 AIH, cytokine levels were normal in all except one sample. A significant decrease in circulating IL-6, IL-8, and TNF-alpha was observed when patients were evaluated during a subsequent remission. We found no significant correlation of cytokine levels with alanine aminotransferase (ALT) activity, total serum gamma-globulins, or prothrombin activity. In patients with cirrhosis, serum IL-8 and IL-6 levels were higher (significantly in the case of IL-8) than those of patients without cirrhosis. In conclusion, activation of the in vivo production of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha appears to be associated with type 1 but not with type 2 AIH.
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PMID:Circulating levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in children with autoimmune hepatitis. 788 14

We investigated the effect of inflammatory cytokines on the intercellular adhesion molecule-1 expression on primary cultured murine hepatocytes. Tumor necrosis factor-alpha, interferon-gamma and interleukin-1 alpha up-regulated the intercellular adhesion molecule-1 expression on hepatocytes in a dose-dependent fashion; however, interleukin-6 did not. On the basis of kinetic analysis, the expression level reached a peak 24 hr after stimulation, and both cycloheximide and actinomycin D inhibited the expression. Furthermore, T lymphocytes bind more to interferon-gamma-stimulated hepatocytes than to unstimulated hepatocytes. The binding was dependent on the concentration of interferon-gamma. The binding was also up-regulated by stimulating T lymphocytes with phorbol myristate acetate. Tumor necrosis factor-alpha and interleukin-1 alpha demonstrated the same effect as interferon-gamma, whereas interleukin-6 did not increase T-lymphocyte adhesion to the hepatocytes. The adhesion induced by interferon-gamma or tumor necrosis factor-alpha was inhibited by antibody against either intercellular adhesion molecule-1 or lymphocyte function-associated antigen-1, a ligand for intercellular adhesion molecule-1, but was not inhibited by CD44 antibodies. These results demonstrate that inflammatory lymphokines enhance the T-lymphocyte adhesion to primary cultured hepatocytes by up-regulating the intercellular adhesion molecule-1 expression on the stimulated hepatocytes by activating the de novo pathway. This mechanism may play an important role in the pathogenesis of hepatitis.
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PMID:Inflammatory cytokines up-regulate intercellular adhesion molecule-1 expression on primary cultured mouse hepatocytes and T-lymphocyte adhesion. 790 80

Serum levels of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in patients with acute viral hepatitis were investigated. Twelve patients suffering from acute viral hepatitis were studied; 8 patients presented with acute hepatitis B, 2 patients with acute hepatitis A, and 2 patients with acute hepatitis C. Serum levels of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were significantly increased in all patients with acute viral hepatitis. Decreased serum levels of all cytokines were noted in four patients with acute hepatitis B during the recovery phase of infection. In addition, IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were undetectable at the end of a follow-up period of 6 months. Our study shows that increased levels of IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha are probably related to hepatitis activity and thus may have some role in hepatocytic injury.
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PMID:Serum levels of interleukin-1 alpha, interleukin-1 beta, interleukin-6, and tumor necrosis factor in patients with acute viral hepatitis. 816 26

Interleukin-6 (IL-6) induction, as detected by bioassay and Northern analysis, was examined in vitro in endothelial cells or astrocytes derived from BALB/c (susceptible) or SJL (resistant) mice following exposure to mouse hepatitis virus (MHV-4) or UV inactivated MHV-4 (UV-MHV-4). In BALB/c endothelial cells, up to 16-fold more IL-6 (> 640 U/ml) was induced, compared to SJL cells which showed a minimal response (40 U/ml), relative to basal levels (< 20 U/ml). In contrast, both BALB/c and SJL astrocytes showed a substantial IL-6 response to MHV-4 and UV-MHV-4 exposure, although a strain difference persisted. Despite strain and cell specific differences in released IL-6, equivalent levels of IL-6 mRNA were induced in all cell types following exposure to MHV-4 or UV-MHV-4.
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PMID:Interleukin-6 induction in vitro in mouse brain endothelial cells and astrocytes by exposure to mouse hepatitis virus (MHV-4, JHM). 838 Aug 7

In order to investigate whether a difference might exist in blood cholesterol and its subtractions between patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, serum cholesterol, HDL-cholesterol, triglycerides and common liver function tests were measured in 138 patients (92 male, 46 female) with biopsy-proven chronic viral hepatitis without cirrhosis. Twenty-four had hepatitis B and 114 hepatitis C. Mean serum cholesterol was lower in HCV-infected in comparison to HBV-infected patients (175 +/- 36 mg/dl vs. 189 +/- 28 mg/dl, p < 0.05). On multivariate analysis, etiology of hepatitis appeared to be associated with the value of serum cholesterol, independently of age, sex and liver synthetic function (improvement of chi-square 4.40, p < 0.05). In patients with HBV infection, circulating tumor necrosis factor-alpha demonstrated a correlation with serum triglycerides (p = 0.618) and an inverse correlation with serum HDL-cholesterol (p = -0.456); in the group of patients with HCV infection, interleukin-6 correlated with triglycerides (p = 0.370) and HDL-cholesterol (p = -0.355). Thus, differences in the mechanisms of liver damage and of viral clearance in hepatitis C in comparison to hepatitis B, reflected in these patients by the levels of circulating cytokines, may be mirrored by differences in their blood lipid composition.
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PMID:Blood lipids of patients with chronic hepatitis: differences related to viral etiology. 920 35

Activation of the N-myc2 oncogene by integration of woodchuck hepatitis virus (WHV) DNA is a central event in woodchuck liver oncogenesis. In this study, we have evaluated the influence of several cellular and viral trans-acting factors and mediators of inflammation on N-myc2 promoter activity in hepatoma cell lines. Ets oncoproteins, including Ets1, Ets2 and PEA3 efficiently activated a chimeric N-myc2 promoter/luciferase reporter gene. By electrophoretic mobility shift assays, we show that Etsl and Ets2 proteins can efficiently bind two consensus Ets sites located within a 59 bp sequence upstream of the N-myc2 transcription start site. Site-directed mutagenesis of these Ets-binding motifs abolished transactivation of the N-myc2 promoter by Ets proteins. Addition of interleukin-6 (IL-6) induced a weak but reproducible activation of the N-myc2 promoter, while IL-1 was ineffective. We further show that the N-myc2 promoter can be transactivated by the hepadna-virus X protein, and that distal promoter sequences are required for both IL-6 and X responsiveness. Similar effects of these factors were observed in the context of the N-myc2 promoter activated by WHV cis-regulatory elements. In view of the high-level expression of the N-myc2 oncogene in most woodchuck liver tumors, the Ets oncoproteins, inflammation-associated cytokine IL-6 and the viral X transactivator might play important roles in hepadnavirus-associated tumorigenesis.
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PMID:Cellular and viral trans-acting factors modulate N-myc2 promoter activity in woodchuck liver tumors. 928 65

Concanavalin A (ConA) activates T lymphocytes and causes T-cell mediated hepatic injury in mice. The intravenous administration of human immunoglobulins has beneficial effects in T-cell mediated diseases such as experimental autoimmune encephalomyelitis and adjuvant arthritis. In the present study, we examined the effects of intravenous immunoglobulins in a mouse model of T-cell mediated, acute liver injury induced by concanavalin A. Balb/c mice were inoculated with 12 mg/kg concanavalin A with or without intravenous immunoglobulins at doses of 0.4, 0.6, 0.8 g/kg body wt. The serum levels of liver enzymes, tumor necrosis factor-alpha, interferon-gamma and interleukin-6 were assayed 2, 6 and 24 h after concanavalin A administration. Intravenous immunoglobulins did not prevent concanavalin A-induced hepatitis, as manifested by elevation of serum aminotransferases and histopathological evaluation. The serum levels of tumor necrosis factor-alpha in mice pretreated with immunoglobulins, measured 2 h after ConA treatment were reduced, while interferon-gamma levels measured 6 h after ConA inoculation were 5-fold higher than control levels. There was no effect of intravenous immunoglobulins on the release of interleukin 6. In conclusion, these results indicate that intravenous immunoglobulin is not effective in preventing T-cell mediated concanavalin A-induced hepatitis. The increased secretion of interferon-gamma and the incomplete suppression of tumor necrosis factor-alpha release may explain the lack of efficacy of intravenous immunoglobulin in this experimental model.
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PMID:Effects of intravenous immunoglobulins on T-cell mediated, concanavalin A-induced hepatitis in mice. 945 32

A defective-interfering (DI) RNA of mouse hepatitis virus (MHV) was developed as a vector for expressing MHV hemagglutinin/esterase (HE) protein. The virus containing an expressed HE protein (A59-DE-HE) was generated by infecting cells with MHV-A59, which does not express HE, and transfecting the in vitro-transcribed DI RNA containing the HE gene. A similar virus (A59-DE-CAT) expressing the chloramphenicol acetyltransferase (CAT) was used as a control. These viruses were inoculated intracerebrally into mice, and the role of the HE protein in viral pathogenesis was evaluated. Results showed that all mice infected with parental A59 or A59-DE-CAT succumbed to infection by 9 days postinfection (p.i.), demonstrating that inclusion of the DI did not by itself alter pathogenesis. In contrast, 60% of mice infected with A59-DE-HE survived infection. HE- or CAT-specific subgenomic mRNAs were detected in the brains at days 1 and 2 p.i. but not later, indicating that the genes in the DI vector were expressed only in the early stage of viral infection. No significant difference in virus titer or viral antigen expression in brains was observed between A59-DE-HE- and A59-DE-CAT-infected mice, suggesting that virus replication in brain was not affected by the expression of HE. However, at day 3 p.i. there was a slight increase in the extent of inflammatory cell infiltration in the brains of the A59-DE-HE-infected mice. Surprisingly, virus titers in the livers of A59-DE-HE-infected mice were 3 log10 lower than that of the A59-DE-CAT-infected mice at day 6 p.i. Also, substantially less necrosis and viral antigen were detected in the livers of the A59-DE-HE-infected mice. This may account for the reduced mortality of these mice. The possible contribution of the host immune system to this difference in pathogenesis was analyzed by comparing the expression of four cytokines. Results showed that both tumor necrosis factor-alpha and interleukin-6 mRNAs increased in the brains of the A59-DE-HE-infected mice at day 2 p.i., whereas interferon-gamma and interleukin-1 alpha mRNAs were similar between A59-DE-HE- and A59-DE-CAT-infected mice. These data suggest that the transient expression of HE protein enhances an early innate immune response, possibly contributing to the eventual clearance of virus from the liver. This study indicates the feasibility of the DI expression system for studying roles of viral proteins during MHV infection.
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PMID:Expression of hemagglutinin/esterase by a mouse hepatitis virus coronavirus defective-interfering RNA alters viral pathogenesis. 950 Oct 44


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