Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum bile acids have been shown to serve as useful indicators of liver disease. We have confirmed these findings and added an analysis of interleukin-1 beta (IL-1 beta) profiles to further differentiate viral hepatitis from toxic liver damage associated with exposure to vinyl chloride (VC) or trinitrotoluene (TNT). The frequency of elevated cholylglycine (CG) was 100%, 75%, and 37.5% in viral hepatitis, VC- and TNT-linked liver injury patients, respectively. The mean levels, expressed in micrograms/dL, were 578, 507, 142, and 65 in hepatitis B, hepatitis non-A non-B, VC and TNT liver injury patients, respectively. Thus, the CG test could detect viral hepatitis and, VC liver injury, and (less frequently) liver injury associated with exposure to TNT. The mean level of IL-1 beta in patients with hepatitis type B was 424 pg/mL and hepatitis non A non B was 384 pg/mL compared with a mean of 33-40 pg/mL in those with VC or TNT-linked liver disease. The IL-1 beta detection test proved further to be an important distinguishing parameter as it was 100% positive in patients with viral hepatitis but only 12.5% to 25% positive in patients with VC/TNT-induced liver damage.
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PMID:Cholylglycine measured in serum by RIA and interleukin-1 beta determined by ELISA in differentiating viral hepatitis from chemical liver injury. 144

Macrophage infiltration is a constant feature of human virus-infected tissues. However, the in situ functional status of these cells remains undetermined. In order to document an activation of macrophages in virus-infected tissues, the expression of IL-1 beta and IL-6 genes was analyzed using in situ hybridization. Several tissues were studied, as well as infections induced by different viruses: lymph nodes infected by HIV-1 (9 cases) or EBV (one case), lungs infected by CMV (5 cases) or adenovirus (1 case), livers infected by HBV, either chronically (2 cases) or acutely (7 cases presenting a fulminant hepatitis). With the exception of fulminant HBV hepatitis, IL-1 beta and IL-6 genes were expressed in all cases. IL-1 beta and IL-6 genes were usually coordinately regulated, as cells containing IL-1 beta or IL-6 mRNA were present in identical amounts and displayed a similar distribution. Analysis of the location and the morphology of monokine gene-expressing cells indicated that both small macrophages and endothelial cells expressed IL-1 beta and IL-6 genes. However, neither tingible body macrophages present in lymph node follicles nor Kupffer cells expressed these genes at a detectable level. Infected cells themselves were also negative for monokine gene expression. These findings indicate that expression of IL-1 beta and IL-6 genes by reactive cells may play a role in viral spreading limitation as well as virus-induced tissue damage.
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PMID:In vivo expression of IL-1 beta and IL-6 genes during viral infections in human. 165 44

The genes for interferon (IFN) alpha, IFN gamma, IL-1 beta, IL-6, and TNF alpha were transcribed at readily detectable levels both in liver biopsies from individuals with normal liver function and in samples of normal viable liver taken for transplantation. These results provided evidence for the concept that such multifunctional cytokines play a role in homeostasis in normal human tissues. In normal human liver, in situ hybridization studies showed that, in the absence of a detectable inflammatory response, both hepatocytes and mononuclear cells exhibited a similar degree of expression of IL-6 mRNA in keeping with the finding that IL-6 is produced by cells of different lineages. The levels of IL-1, IL-6, and TNF mRNA were found to be markedly reduced in extracts of the livers of patients with primary biliary cirrhosis and other forms of autoimmune liver disease at a time when extensive liver lesions were apparent, compared to the levels of expression of these cytokines in the livers of normal individuals. The reduced expression of IL-1, IL-6, and TNF mRNAs appeared to be a specific effect and not due to a general reduction in RNA synthesis as the IFN alpha, IFN gamma and actin mRNAs were expressed at similar levels in both normal and diseased livers. The levels of IL-1 beta, IL-6, and TNF mRNAs were also reduced in samples of liver from a patient with a drug induced fulminant hepatitis suggesting that this specific pattern of altered cytokine gene expression was characteristic of the advanced stage of severe liver disease.
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PMID:Genes for interleukin-1, interleukin-6, and tumor necrosis factor are expressed at markedly reduced levels in the livers of patients with severe liver disease. 177 64

Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV-JHM) develop a demyelinating encephalomyelitis several weeks after infection. Astrogliosis and infiltration of inflammatory cells are prominent findings in the brains and spinal cords of infected mice. In this report, astrocytes in infected spinal cords were analyzed for expression of three pleiotropic cytokines, TNF-alpha, IL-1 beta, and IL-6; Type 2 nitric oxide synthase (iNOS); and MHC class I and II antigen. The data show that all three cytokines and iNOS are expressed by astrocytes in chronically infected spinal cords. These activated astrocytes are localized to areas of virus infection and demyelination, although most of the astrocytes expressing these proteins are not MHV-infected. MHC class I and II antigen can be detected in these spinal cords as well, but not in cells with the typical morphology of astrocytes. TNF-alpha, IL-6, and iNOS are also evident in the brains of mice with MHV-induced acute encephalitis, but in marked contrast to the results obtained with the chronically infected mice, most of the cells expressing these cytokines or iNOS had the morphology of macrophages or other mononuclear cells and very few appeared to be astrocytes. Additionally, astrocytes and, most likely, oligodendrocytes are infected in the spinal cords of mice with chronic demyelination. These results are consistent with a role for both viral infection of glial cells and high localized levels of proinflammatory cytokines and nitric oxide in the demyelinating process in mice infected with MHV-JHM. They also show that analogously to the human demyelinating disease, multiple sclerosis, astrocytes are a major cellular source for these cytokines in mice with chronic, but not acute disease.
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PMID:Activation of astrocytes in the spinal cord of mice chronically infected with a neurotropic coronavirus. 749 73

Inflammatory cytokines such as tumor necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) and interleukin-1 beta (IL-1 beta) play important roles in the mechanisms of hepatitis. The effects of these cytokines on the expression of vascular cell adhesion molecule-1 (VCAM-1) in hepatocytes were examined. TNF alpha and IL-1 beta but not IFN gamma or IL-6 induced VCAM-1 expression on primary cultured murine hepatocytes in a dose- and a time-dependent fashion. TNF alpha is significantly more effective than IL-1 beta on the induction of VCAM-1 expression. The results of RT-PCR demonstrate that these cytokines regulate VCAM-1 expression at mRNA level. These results suggest that TNF alpha and IL-1 beta participate in the pathogenesis of hepatitis via induction of VCAM-1 molecules on hepatocytes.
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PMID:Tumor necrosis factor alpha and interleukin-1 beta but not interferon gamma induce vascular cell adhesion molecule-1 expression on primary cultured murine hepatocytes. 753 41

We examined the interactive effect of several cytokines (interleukin-1 beta [IL-1 beta], tumor necrosis factor alpha [TNF-alpha], interferon gamma [IFN-gamma], IL-6, IFN-alpha/beta, and hepatocyte growth factor [HGF]) presumably involved in hepatitis, on primary cultured murine hepatocytes. Among these cytokines, only IFN-gamma induced LDH release from hepatocytes in both time- and dose-dependent fashions. The cytotoxic effect was inhibited by antiserum-containing anti-mouse IFN-gamma monoclonal antibodies (R4-6A2). Moreover, intriguingly, IFN-gamma induced DNA fragmentation in the hepatocytes in a time- and dose-dependent fashion according to the gel electrophoresis of genomic DNA and flow cytometry analysis. These results suggest that the cytotoxic effect of IFN-gamma on hepatocytes was caused by inductive apoptosis. The LDH release and DNA fragmentation induced by IFN-gamma were inhibited by HGF in a dose-dependent manner, whereas they seemed to be accelerated by TNF-alpha. Flow cytometry analysis of the nuclei of treated hepatocytes confirmed the interactions in DNA degradation. The DNA synthesis of cultured hepatocytes was also reduced by IFN-gamma but recovered by hepatocyte growth factor. Taken together, IFN-gamma is presumed to be a critical cytokine in hepatic damage, and the network composed of IFN-gamma, TNF-alpha, and HGF may play an important role in the regulation of liver injury.
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PMID:Protective effect of hepatocyte growth factor on interferon-gamma-induced cytotoxicity in mouse hepatocytes. 776 3

Fulminant hepatic failure (FHF) is characterized by massive necroinflammation of the liver tissue and is associated with high mortality. Serum concentrations of IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-1 receptor antagonist (IL-1Ra) were measured in 30 patients with FHF and in 23 patients with acute hepatitis (AH) before start of treatment and in 23 healthy controls. Levels of all four molecules were increased significantly in FHF compared with AH, in which values were higher than in the healthy controls. High serum levels of IL-1 beta and a significantly reduced ratio of IL-1Ra to IL-1 beta (IL-1Ra/IL-1 beta) were observed in FHF patients who subsequently died compared with subjects who survived. TNF-alpha and IL-6 concentrations were correlated with levels of human hepatocyte growth factor (hHGF), an index of hepatocyte regeneration. Although serum cytokine levels varied considerably between patients within each group studied, it is suggested that the striking elevation in proinflammatory cytokine levels in FHF may reflect both the insufficiency of hepatitis virus elimination and a failure to control a vicious cytokine cascade leading to overwhelming hepatocyte destruction rather than regeneration. The high cytokine levels observed in these patients and the significantly elevated IL-1Ra/IL-1 beta ratio in FHF patients who survived compared with those who did not suggest the possible therapeutic use of cytokine antagonists for the control of this life-threatening disease.
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PMID:Circulating proinflammatory cytokines (IL-1 beta, TNF-alpha, and IL-6) and IL-1 receptor antagonist (IL-1Ra) in fulminant hepatic failure and acute hepatitis. 792 88

To investigate the mechanism by which viruses are cleared from neurons in the central nervous system, we have utilized a mouse model involving infection with a neurotropic variant of mouse hepatitis virus (OBLV60). After intranasal inoculation, OBLV60 grew preferentially in the olfactory bulbs of BALB/c mice. Using in situ hybridization, we found that viral RNA localized primarily in the outer layers of the olfactory bulb, including neurons of the mitral cell layer. Virus was cleared rapidly from the olfactory bulb between 5 and 11 days. Athymic nude mice failed to eliminate the virus, demonstrating a requirement for T lymphocytes. Immunosuppression of normal mice with cyclophosphamide also prevented clearance. Both CD4+ and CD8+ T-cell subsets were important, as depletion of either of these subsets delayed viral clearance. Gliosis and infiltrates of CD4+ and CD8+ cells were detected by immunohistochemical analysis at 6 days. The role of cytokines in clearance was investigated by using an RNase protection assay for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-alpha), TNF-beta, and gamma interferon (IFN-gamma). In immunocompetent mice there was upregulation of RNA for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma at the time of clearance. Nude mice had comparable increases in these cytokine messages, with the exception of IFN-gamma. Induction of major histocompatibility complex class I (MHC-I) molecules on cells in infected brains was demonstrated by immunohistochemical analyses in normal and nude mice, suggesting that IFN-gamma may not be necessary for induction of MHC-I on neural cells in vivo.
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PMID:Cytokine induction during T-cell-mediated clearance of mouse hepatitis virus from neurons in vivo. 805 31

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

Hepatocyte growth factor (HGF) is the most potent mitogen of mature hepatocytes in primary culture, and is a molecule composed of 69 kD alpha-chain and 34 kD beta-chain. HGF predominantly acts on various epithelial cells as a mitogen, motogen and a morphogen. HGF mRNA and HGF protein increases rapidly in the liver and plasma of rats with liver injury such as hepatitis, ischemia, physical crush and partial hepatectomy. Production of HGF in the liver occurs in Kupffer cells, sinusoidal endothelial cells, and Ito cells, but not in hepatocytes. HGF mRNA is also rapidly increased in the intact organs such as lung, kidney and spleen. Thus, HGF may act as a hepatotrophic factor for liver regeneration through two mechanisms: a paracrine mechanism and an endocrine mechanism. Moreover, intravenously injected HGF enhances liver regeneration and protects hepatitis in vivo. Consequently, HGF may prove to be useful for the clinical treatment of patients with liver disease. Recently, we found a factor which specially appears in the blood of rats with organ injury and increases the synthesis of HGF, and it was named "injurin". IL-1 alpha and IL-1 beta are also positive regulators for the expression of the HGF gene, while TGF-beta and Dexamethazone down-regulate HGF expression.
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PMID:[Molecular biology of hepatocyte growth factor (HGF)]. 838 41


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