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)

Resistance of mice to mouse hepatitis virus type 3 (MHV3) infection is genetically determined. Normal adult A/J mice are resistant, and BALB/c mice are susceptible. Higher titers of virus and interferon (IFN) in vivo were found in MHV3-infected BALB/c mice compared with A/J mice. In vitro activation of macrophages (M phi) by lipopolysaccharide (LPS) delayed MHV3 replication only in cells that originated from A/J mice, although cell populations from both A/J and BALB/c mice were able to synthesize comparable amounts of IFN-alpha/beta. Using specific antibodies, we have shown that the delayed MHV3 replication in LPS-activated A/J M phi was due, in part, to IFN-alpha/beta. A/J M phi were found to be more sensitive to IFN-gamma than to IFN-alpha/beta, and BALB/c M phi did not develop an antiviral state to either IFN. Cultured spleen cells from A/J mice synthesized more IFN-gamma than BALB/c spleen cells after specific or non-specific stimulation. The results indicate that IFN-activated M phi may play a crucial role in the resistance to MHV3 infection. Since IFN-gamma is produced in large amounts by A/J spleen cells after specific stimulation with MHV3 and is efficient in activating the A/J M phi, a T cell-dependent mechanism is likely to be involved.
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PMID:A major role of macrophage activation by interferon-gamma during mouse hepatitis virus type 3 infection. I. Genetically dependent resistance. 256 Apr 61

Recent studies have shown that gamma-interferon (IFN-gamma) induces the expression of Ia antigen on astrocytes. This observation is of immunological significance because such activated astrocytes can act as antigen-presenting cells, as demonstrated with myelin basic protein for antigen-specific encephalitogenic T-cell lines. However, the lack of lymphatic drainage in brain and the presence of the so-called blood-brain barrier restricting traffic of cells and macromolecules suggests that IFN-gamma may not be readily available, at least during the initial phases of viral infections. The question therefore arises as to whether astrocytes can be induced to express Ia antigens by other signals directly related to viral infection and possibly independent of IFN-gamma. In the present report we demonstrate that a neurotropic murine hepatitis virus induces expression of Ia antigen on astrocytes in tissue culture without infection, rendering these brain cells competent to participate directly in the immune response to a viral infection.
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PMID:Viral particles induce Ia antigen expression on astrocytes. 300 3

Interferon (IFN) added to cell culture systems alters the capacity of the cells to produce IFN when appropriately stimulated. To evaluate the effects of in vivo administration of IFN on the production of IFN by peripheral blood mononuclear cells (PBMCs), we studied patients with chronic type-B hepatitis who received doses of recombinant human leukocyte (alpha) IFN (IFN-alpha) ranging from 5 X 10(6) units daily to 60 X 10(6) thrice weekly. The production of endogenous IFN stimulated by specific inducers (Sendai virus for IFN-alpha; phytohemagglutinin for IFN-gamma) was studied in cell cultures containing PBMCs obtained from patients before or during courses of IFN treatment. In untreated controls, no change in the mean capacity of PBMCs to produce IFN-alpha was noted after 2 weeks. Priming of endogenous IFN-alpha production, as reflected by earlier production of IFN by PBMCs in culture, occurred in all treated patients irrespective of the dose of IFN-alpha received. Whereas mean 24-hour (total) endogenous IFN-alpha fell in all treatment groups, the response was highly variable in individual patients and half showed no change in total production. Individual variations in endogenous IFN-alpha production were unrelated to serum IFN levels achieved during treatment, changes in serum aminotransferase levels, reduction of hepatitis B virus replication during therapy, or the proportions of T and B lymphocytes in culture. In contrast to the changes in IFN-alpha production, IFN-gamma production by PBMCs was not affected by IFN-alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of recombinant human leukocyte interferon treatment of endogenous interferon production in patients with chronic type-B hepatitis. 308 73

Regarding of microbiological aspects of arthritis three forms of joint diseases are under investigation: the septic arthritis, the reactive arthritis and the Rheumatoid Arthritis. In 95% of patients with septic arthritis microorganisms as causative agents responsible for the disease are described: Staphylococci, Streptococci, some gram-negative bacteria. By an haematogenic route of infection predominantly patients with immunosuppressive therapy are altered. In newborns and children septic arthritis is to observe more rarely. A reactive arthritis is a postinfectious sterile process in dependence on an infection occurred at an earlier time. As etiologic agents Yersinia, Enterobacteriaceae and Campylobacter have been discovered. 80% of the patients suffering such a reactive arthritis are carrier of the HLA-B27 system. The etiology of the Rheumatoid Arthritis is an open, unanswered problem. Of importance are: immunogenetic conditions, autoimmune phenomena, endocrinologic, dietetic and psychologic factors as well as bacteria and viruses as causative agents: cocci, bacilli, Diphteroids, endoparasitic bacteria (Listeria, L-forms, Mycoplasma, Chlamydiae), viruses (Adeno-, Mumps-, Measles-, ECHO-, Coxsackie-A- and B-, Hepatitis-, Cytomegalo-, Para-influenza-, Retro-, Parvo- and Rubella viruses). In the last years the EBV is of interest covering the question of a distinct virus persistence in tissues and the adequate limiting factors. Perhaps a defect of the hu-IFN-gamma-system might be of immunopathological and clinical significance.
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PMID:[Microbiologic aspects of inflammatory joint diseases]. 367 41

Methisoprinol (Isoprinosine), a purine derivative, has been shown to exert a number of immunopharmacological effects, both in vitro and in vivo, in animal and human studies. The agent, somehow mimicking the effects of thymic factors, induces the appearance of phenotypic markers of differentiation on immature precursor T cells; enhances the proliferative response of murine and human lymphocytes to mitogens or antigens, augments helper or suppressor T cell functions and increases the production of lymphotoxin a lymphokine. It has also been shown that this drug can potentiate the effects of macrophage activating factor to stimulate macrophage, and of interferon to protect mice against experimental viral and tumor challenges. In humans, beneficial results have been reported from clinical trials testing the effects of methisoprinol in a variety of diseases including subacute sclerosing panencephalitis (SSPE), acute viral encephalitis, recurrent mucocutaneous infections due to type I and II Herpes viruses as well as in immune restoration of cancer patients with immunodepression following radiotherapy. The drug is also being studied in immunopathological disorders such as rheumatoid arthritis, systemic lupus erythematosus. Sjogren's disease and type A hepatitis. The large spectrum of effects of methisoprinol on a number of immune parameters, the increasing evidence of its therapeutic value in several pathological conditions and its safety of use qualifies this drug as an interesting immunoregulating agent.
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PMID:A recent overview on in vitro and in vivo immunological activities of methisoprinol. 617 7

When the peripheral blood lymphocytes from patients with drug-induced allergic hepatitis were stimulated with a specific drug in vitro in the presence of a liver cytosol fraction containing liver specific antigen, lymphocyte transformation was seen in eight out of 11 patients. The macrophage activating factor (MAF), a kind of lymphokines, was also detectable in the culture medium of activated lymphocytes from seven out of eight patients who showed positive blastogenesis evaluated the uptake of 3H-glucosamine into macrophages. MAF-activated macrophages exhibited a cytotoxic effect on separated liver cells resulting in a marked inhibition of albumin synthesis. This macrophage-mediated cytotoxicity was also observed in eight out of 11 patients who showed positive lymphocyte transformation. These observations suggest that macrophage-mediated cytotoxicity may play some role in the pathogenesis of drug-induced allergic hepatitis.
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PMID:Immunological studies on drug-induced allergic hepatitis--hepatocellular injury by macrophage-mediated cytotoxicity. 698 26

The possible involvement of cell-mediated immune response to liver specific lipoprotein (LSP) in the pathogenesis of liver injury was investigated. The subjects were consisted of one patient with acute hepatitis, five cases with chronic active hepatitis and one case with chronic failure inactive hepatitis. When peripheral blood lymphocytes from these patients were cultured in the presence of LSP and lymphocyte transformation was determined by measuring the uptake of [3H]-thymidine into the acid-insoluble materials, positive blastogenesis was seen in three cases with chronic active hepatitis. Furthermore, when peripheral blood lymphocytes from halothane-induced cholestatic hepatitis were cultured with offending drug in the presence of LSP and lymphocyte transformation was determined, a positive blastogenesis was seen. The factor which activated Kupffer cells (KCAF), a kind of lymphokine, was also detectable in the culture medium of activated lymphocytes from four patients who showed positive blastogenesis by estimating [3H]-glucosamine incorporation into Kupffer cells. The macrophage activating factor (MAF) was detectable in culture medium of activated lymphocytes from three patients who showed positive blastogenesis by estimating [3H]-glucosamine incorporation into macrophages. Furthermore, the KCAF-activated Kupffer cells and MAF-activated macrophages were shown to be cytotoxic for the isolated liver cells causing marked inhibition of albumin synthesis. The observations suggest that Kupffer cell-mediated cytotoxicity and macrophage-mediated cytotoxicity play a role in the pathogenesis of liver disease.
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PMID:The possible involvement of Kupffer cell-mediated hepatocytotoxicity in the pathogenesis of liver injuries. 702 42

The possible involvement of cell-mediated immune responses to liver-specific protein in the pathogenesis of liver injury was investigated. The subjects consisted of seven patients with acute hepatitis, 12 cases with chronic active hepatitis, four cases with chronic inactive hepatitis, and three cases with liver cirrhosis. When peripheral blood lymphocytes from these patients were cultured in the presence of liver specific protein, and lymphocyte transformation was determined by measuring the uptake of [3H]thymidine into acid-insoluble materials, positive blastogenesis was seen in two cases with acute hepatitis and in six cases with chronic active hepatitis. The macrophage activating factor (MAF), a kind of lymphokine, was also detectable in the culture medium of activated lymphocytes from six patients who showed positive blastogenesis by estimating [3H]glucosamine incorporation into macrophages. Furthermore, the MAF-activated macrophages wer shown to be cytotoxic for the isolated liver cells causing marked inhibition of albumin synthesis. This macrophage-mediated cytotoxicity was detected in eight cases that showed positive lymphocyte transformation. These observations suggest that macrophage-mediated cytotoxicity plays a role in the pathogenesis of chronic active hepatitis.
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PMID:Immunological studies on chronic active hepatitis: possible involvement of macrophage-mediated cytotoxicity in its immunopathogenesis. 704 38

To investigate how T cells are involved in hypersensitivity reactions to drugs that become immunogenic after metabolization, e.g., sulfonamides and antiepileptics, we analyzed in vitro the drug-induced activation of CD4+ and CD8+ T cell subsets, cytokine secretion, TCR V beta distribution, and proliferation of T cells from four drug-allergic individuals. In addition, the activation parameters CD25 and HLA-DR were analyzed in vivo on CD4+ and CD8+ T cells from five patients with acute drug allergies, some of them with anticonvulsant hypersensitivity syndrome with hepatitis. Our results show that, in vitro, drug-induced proliferation of PBMC from patients with allergy to sulfamethoxazole, phenytoin, or carbamazepine was specific and dose dependent. CD4+ as well as CD8+ T cells expressed elevated levels of CD25 and HLA-DR molecules after drug stimulation. Drug-activated lymphocytes secreted high amounts of IL-5 and normal or low levels of IL-2, IFN-gamma, IL-4, and TNF-alpha. An enhanced expansion of TCR V beta 17+ T cells 9 days after in vitro stimulation with sulfamethoxazole was observed in one patient with sulfamethoxazole allergy. The drug specificity of the in vitro-activated T cells was confirmed by generation of different sulfamethoxazole specific T cell lines and CD4+ and CD8+ T cell clones. T cell analysis of patients with acute drug allergy to carbamazepine, phenytoin, allopurinol, or paracetamol confirms the in vitro data, because all patients had activated CD4+ or CD8+ T cells in the circulation. Our data clearly show the involvement of drug-specific T cells in drug allergies.
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PMID:Activation of drug-specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine. 760 18

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


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