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)

Pretreatment with recombinant human granulocyte CSF (G-CSF) protected mice in two different models of septic shock. Intravenous injection of 250 micrograms/kg G-CSF to mice prevented lethality induced by 5 mg/kg LPS. Injection of 50 micrograms/kg G-CSF protected galactosamine-sensitized mice against LPS-induced hepatitis. In either case, this protection was accompanied by a suppression of LPS-induced serum TNF activity. In contrast, when galactosamine-sensitized mice were pretreated with 50 micrograms/kg murine recombinant granulocyte/macrophage CSF instead of G-CSF and subsequently challenged with LPS, serum TNF activity was significantly enhanced and mortality was increased. The suppressive effect of G-CSF on LPS-induced TNF production was also demonstrated in rats. In vivo, no TNF was detectable in the blood of LPS-treated rats, which had been pretreated with G-CSF. Ex vivo, alveolar macrophages, bone marrow macrophages, Kupffer cells, or peritoneal macrophages prepared from G-CSF-treated rats produced significantly less TNF upon stimulation with LPS than corresponding populations from control rats. However, when these macrophage populations were incubated with G-CSF in vitro, LPS-induced TNF production was unaffected. These data suggest that the G-CSF-mediated suppression of TNF production is not a direct effect of G-CSF on macrophages. To examine whether, independent of the protection against LPS, G-CSF treatment still activated neutrophils, it was demonstrated that granulocytes from G-CSF-treated rats were primed for PMA-induced oxidative burst and for ionophore/arachidonic acid-stimulated lipoxygenase product formation. The experiments of this study support the notion that G-CSF is a negative feedback signal for macrophage-derived TNF-alpha production during Gram-negative sepsis.
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PMID:Granulocyte colony-stimulating factor treatment protects rodents against lipopolysaccharide-induced toxicity via suppression of systemic tumor necrosis factor-alpha. 137 68

Pretreatment with the reactive oxygen species scavengers superoxide dismutase (SOD) and catalase or with the xanthine oxidase inhibitor allopurinol protected mice against hepatitis induced by the combined administration of lipopolysaccharide (endotoxin) and D-galactosamine. In the sera of protected animals no tumor necrosis factor (TNF alpha) was detectable in contrast to abundant amounts in the sera of injured control animals. A similar protection by the suppression of systemic TNF alpha was observed following the pretreatment of mice with polystyrene-coupled SOD prior to endotoxic challenge. Both pretreatments were ineffective when hepatitis was evoked by administration of the mediator TNF alpha instead of endotoxin. These findings indicate that the formation of extracellular reactive oxygen species is a condition needed to induce the release of TNF alpha and thus to mediate endotoxin-induced toxicity.
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PMID:A link between extracellular reactive oxygen and endotoxin-induced release of tumour necrosis factor alpha in vivo. 155 88

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

The role of tumor necrosis factor alpha (TNF alpha) in the immunopathological events induced by infection with lymphocytic choriomeningitis (LCM) virus (LCMV) was assessed by treatment of C57Bl/6 mice with a sheep antibody to murine TNF alpha antiserum to strongly interfere with anti-Listeria host defense. However, despite its effectiveness in Listeria infections in vivo, antibody to TNF alpha used at 6 x 10(4) neutralizing units per day subcutaneously had no detectable influence on the kinetics of maturation of antiviral cytotoxic T-cell activity, inflammatory processes, or clearance of virus. First, onset and severity of LCMV-induced hepatitis, as assessed by cytotoxic T-cell activity, viral titers in the liver, serum liver enzyme values, and histology, were not detectably affected by antibody to TNF alpha. Second, incidence of lethal LCM disease after intracerebral infection and the kinetics of the primary footpad swelling reaction observed after local foot inoculation were not altered by anti-TNF alpha antibody treatment. From the data presented we conclude that TNF alpha as assayed by in vivo therapy with a polyclonal anti-TNF alpha antibody plays no detectable role in the host reaction against LCMV.
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PMID:Treatment with anti-tumor necrosis factor alpha does not influence the immune pathological response against lymphocytic choriomeningitis virus. 212 99

We determined serum and peripheral blood mononuclear cell (PBM) TNF activity in 8 healthy donors and 47 patients with hepatitis by using 3H-thymidine release method of Maennel et al. The serum TNF levels were significantly increased in chronic active hepatitis and subacute hepatic failure (13.8 +/- 6.3, and 19.4 +/- 3.9). Patients with serum bilirubin more than 10 mg/ml showed a higher serum TNF level than those with lower serum bilirubin. A significant elevation of TNF level was also observed in patients with positive endotoxemia or concurrent bacterial or viral infections. Experimental liver injury in Wistar rats induced by galactosamine (GLN) and LPS produced marked increase of serum TNF level and submassive liver necrosis. It is noteworthy that normal serum TNF and markedly ameliorated liver injury were observed in rats that received combined treatment with GLN, LPS and hepatopoietin (HPN), a low molecular peptide extracted from suckling porcine liver. In vitro, HPN also significantly suppressed TNF activity when it was co-incubated with PBM and LPS. An encouraging result was observed in preliminary clinical trial of HPN for the treatment of subacute liver failure. It suggests that Serum TNF appears to play an important role in the pathogenesis of liver injury from viral hepatitis and HPN seems to be a protection in liver injury against TNF activity.
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PMID:[Tumour necrotic factor (TNF) in the pathogenesis of liver necrosis in viral hepatitis and strategy for its prevention and treatment]. 217 82

Mice pretreated by intravenous injection of 42 mg/kg of the serine protease inhibitor alpha 1-antitrypsin prior to a hepatotoxic dose of D-galactosamine/lipopolysaccharide (GalN/LPS) were fully protected against hepatitis. Pretreatment with alpha 1-antitrypsin with doses up to 300 mg/kg at different times failed to protect galactosamine sensitized animals against tumor necrosis factor alpha (TNF alpha)-induced hepatitis. No bioactive TNF alpha was detectable in serum of mice protected against GalN/LPS-induced hepatitis by pretreatment with alpha 1-antitrypsin. In contrast, abundant amounts of TNF were found in sera of GalN/LPS-treated control animals. It is concluded that a serine protease sensitive to alpha 1-antitrypsin provides bioactive TNF alpha by proteolytic cleavage of a TNF alpha precursor.
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PMID:In vivo evidence for protease-catalysed mechanism providing bioactive tumor necrosis factor alpha. 222 15

Subtoxic doses of endotoxin (salmonella abortus equi lipopolysaccharide, LPS) (5 micrograms/kg i.p.) or tumor necrosis factor alpha (TNF alpha) (15 micrograms/kg i.v.) induced fulminant hepatitis within 8 hr, when mice had been sensitized by a subtoxic dose of D-galactosamine (700 mg/kg i.p.). LPS-treatment led to the release of TNF into the circulation, independently of the presence of D-galactosamine. The TNF-dependent development of hepatitis was accompanied by a severe lymphopenia and neutrophilia as assessed by leukocyte differential count. The total leukocyte count was not significantly affected. Lymphopenia and neutrophilia were induced by LPS or TNF alpha alone; however, the differential count was not influenced by D-galactosamine. A quantity of 260 micrograms/kg phorbol myristate acetate (PMA) i.p. or 5 micrograms/kg platelet activating factor (PAF) i.v. or 3.3 mg/kg N-formyl-methionyl-leucyl-phenylalanine methylester (FMLP) i.v. or 167 mg/kg zymosan i.v. also caused lymphopenia and neutrophilia in mice. However, none of these agents induced the production of systemic TNF and therefore failed to induce hepatitis in D-galactosamine-sensitized mice. In LPS-insensitive C3H/HeJ mice administration of LPS produced neither differential count changes nor hepatitis while both events were observed when TNF alpha was given. This shows that TNF alpha alone gives rise to lymphopenia/neutrophilia as well as hepatitis independent of LPS. When the action of TNF alpha was blocked by anti TNF alpha antiserum pretreatment of LPS-sensitive mice, the animals were protected against LPS-induced hepatitis. However, lymphopenia and neutrophilia still occurred to a similar extent. The involvement of a putative additional mediator of LPS-induced leukocyte alterations was checked. The findings suggest that this mediator, if present, is different from IL-1, IL-2, eicosanoids or superoxide. We conclude from our findings that changes in leukocyte numbers and composition following D-galactosamine LPS or D-galactosamine/TNF alpha administration is an epiphenomenon rather than a causal event of leukocyte stimulation in the process of inducing a fulminant hepatitis in mice.
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PMID:Leukocyte alterations do not account for hepatitis induced by endotoxin or TNF alpha in galactosamine-sensitized mice. 240 85

Our study was undertaken to determine whether human recombinant interferon alpha(rIFN alpha), gamma(rIFN gamma), and tumor necrosis factor alpha(rTNF alpha) exert an effect on the HLA-A, B, C expression of human liver cell lines. The HLA-A, B, C expression was assayed by immunoperoxidase staining and enzyme-linked immunosorbent assay. rIFN alpha and gamma enhanced the HLA-A, B, C expression of the three cell lines tested, Chang cells, SK-Hep-1, and PLC/PRF/5. The activity of rIFN gamma proved more than 8000 times more potent than that of rIFN alpha in Chang cells, 30 times in SK-Hep-1, and 20 times in PLC/PRF/5, respectively. rTNF alpha also enhanced the HLA-A, B, C expression of the three cell lines. The enhancement of HLA-A, B, C expression by rIFN alpha and gamma reached a peak on day 3, and that by rTNF alpha on day 5. These findings suggest that IFN alpha, IFN gamma, and TNF alpha may play similar roles in enhancement of HLA-A, B, C expression of hepatocytes in hepatitis and hepatoma cells.
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PMID:Effect of interferon alpha, gamma, and tumor necrosis factor alpha on the HLA-A, B, C expression of cell lines derived from human liver. 249 41

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

Plasma soluble tumor necrosis factor receptor (sTNFR) was detected by radioimmunoprecipitation-polyethylene glycol assay in 64 patients with viral hepatitis B. The levels of two distinct receptors (sTN-FR1 and sTNFR2) were significantly higher in chronic severe hepatitis (CSH) followed by chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and acute hepatitis (AH) or controls (P < 0.01). A more markedly increased sTNFR was observed in patients with high SB (> 342 mumol/L), low Pa (< 20%), and secondary infection or fatal outcome. For patients with 20% below of sTNFR levels, the increase of TNF was proportional to that of sTNFR. But, for patients with exceeding 20% of sTNFR, the ratio of TNF/sTNFR became higher. The ratio of TNF to sTNFR may be greatly indicative to determine the clinical severity and outcome. Administration of sTNFR could prevent the adverse pathologic sequence caused by the exaggerated TNF and open a new therapeutical field.
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PMID:[Relation of plasma soluble tumor necrosis factor receptor to tumor necrosis factor and clinical features of hepatitis B]. 784 35


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