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)

Interleukin-18 (IL-18) is a recently cloned cytokine, produced from activated macrophages, including Kupffer cells. IL-18 is originally called interferon-gamma inducing factor (IGIF), due to its action to induce IFN-gamma production from Th 1 cells and NK cells. However, recent studies suggested that, IL-18 also enhances expression of FasL and NK activity as well as GM-CSF production. These data revealed this novel cytokine is pleiotropic. Recently, cDNA encoding human IL-18 receptor (IL-18R) was cloned. And, we had cloned murine IL-18R cDNA by RT-PCR, using human IL-18R sequence. Northern blot analysis of cytoplasmic RNA from T cells stimulated with IL-12 clearly demonstrated that, T cells stimulated with IL-12 induced high level of IL-18R-mRNA, whereas non-stimulated T cells did not have. Interestingly, we had several reports, indicated the involvement of IL-18 on the progressions of pathogenicity in chronic inflammatory diseases, including endotoxin-shock, hepatitis and autoimmune-diabetes. We need further studies to reveal physiological roles of this novel cytokine in various inflammatory or autoimmune diseases.
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PMID:[IL-18 and IL-18 receptor]. 970 56

Propagermanium is an organic germanium compound with immunopotentiating activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute liver injury induced with Corynebacterium parvum (C. parvum) and lipopolysaccharide (LPS) injection. Oral pretreatment with propagermanium decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in a dose-dependent manner. Significant attenuation of ALT and AST activity was obtained at a dose of 3 mg/kg. Administration of propagermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examination revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-positive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine levels increased rapidly after LPS injection, causing severe hepatitis. Notably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production of interleukin-12 (IL-12). These results indicate that propagermanium inhibits cell infiltration in the liver and cytokine production, and improves massive liver injury in C. parvum/LPS mice.
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PMID:Hepatoprotective effect of propagermanium on Corynebacterium parvum and lipopolysaccharide-induced liver injury in mice. 971 10

The liver injury in the concanavalin A (Con A)-induced mouse hepatitis model has been well studied. However, there has been little study on the effects of Con A on extrahepatic organs. The aim of the present work was to determine the effects of Con A on the spleen, kidney and lung. A histopathological study showed that Con A (15 mg/kg, i.v.) administration affects not only the liver, but also all these extrahepatic organs. Messenger RNA expression was studied by the using polymerase chain reaction. Treatment with Con A induced interleukin-2 mRNA in the spleen, but only slightly induced it in the kidney. The mRNAs of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were induced in all these organs. At 24 hr after Con A treatment, the expression of IFN-gamma mRNA, but not that of TNF-alpha mRNA, was inhibited by cyclosporine A (50 mg/kg, i.p.), suggesting that Con A induced these cytokine mRNAs through different mechanisms. In the kidney and lung, CD4+ and CD8+ T-cell infiltration was suggested by the Con A-induced CD4 and CD8 mRNAs. The present study showed the histopathological effects of Con A and Con A-induced cytokine mRNA expression on the spleen, kidney and lung.
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PMID:Expression of cytokine mRNA in extrahepatic organs in a mouse concanavalin A-hepatitis model. 971 69

Expression of Bgp1a, a glycoprotein that serves as receptor for mouse hepatitis virus-A59 has been analyzed in various mouse tissues and correlated with the pathogenicity that this virus induces in the corresponding organs. Expression of Bgp1a was observed in many cells of epithelial origin, including hepatocytes and endothelial cells. It was also shown on macrophages and B lymphocytes. Bgp1a localization may easily explain infection and lysis of some cell types like hepatocytes. In contrast, other cell types that express the viral receptor are not infected after in vivo inoculation with mouse hepatitis virus-A59, which may be due to inaccessibility of the receptor to the virus during mouse infection, or to resistance to this virus in some cell types. This may account for the ability of the blood-brain barrier to prevent mouse hepatitis virus-A59 spreading into the central nervous system. In other organs, the virus may induce pathogenesis indirectly, resulting in the destruction of cells that do not express Bgp1a, like thymic lymphocytes, or else impair cell functions such as cytokine and immunoglobulin production by macrophages and B lymphocytes, respectively.
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PMID:Role of mouse hepatitis virus-A59 receptor Bgp1a expression in virus-induced pathogenesis. 978 31

Hepatitis B virus (HBV) transgenic mice that are immunologically tolerant to HBV-encoded Ags represent a model of chronic HBV infection suitable for the development of therapeutic immunization strategies before testing in humans. Five lineages of HBV transgenic mice were immunized with plasmid DNA that encodes hepatitis B surface Ag (HBsAg) or with cytokine-activated bone marrow-derived dendritic cells (DCs) in an attempt to break tolerance to HBsAg at the B and T cell levels. DNA immunization stimulated an Ab response but not a cytotoxic T lymphocyte response to HBsAg in two of the five transgenic lineages studied. In contrast, infusion of activated transgenic or nontransgenic DCs stimulated a splenic CTL response in all three transgenic lineages immunized in this manner at precursor frequencies comparable to those in nontransgenic mice, indicating that DC function is normal, and HBsAg-specific CTLs are present but functionally silent in these transgenic animals. Importantly, none of the animals developed hepatitis or displayed suppressed viral gene expression or replication following either DNA immunization or DC administration even in the presence of anti-hepatitis B surface (HBs) Abs and HBs-specific CTLs. These results indicate that Ag presentation by cytokine-activated DCs can break tolerance and trigger an anti-viral CTL response in HBV transgenic mice, and they suggest that this strategy is more efficient than DNA immunization in this setting. Nonetheless, more efficient immunization strategies are needed to stimulate an immune response of sufficient quality and magnitude to achieve an immunotherapeutic antiviral effect.
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PMID:Dendritic cell immunization breaks cytotoxic T lymphocyte tolerance in hepatitis B virus transgenic mice. 979 77

Elevated concentrations of plasma proinflammatory cytokines have been detected in patients with alcoholic hepatitis (AH) and in a model of lipopolysaccharide-induced hepatitis in ethanol-fed Wistar rats. These cytokines have been implicated in the pathogenesis of the liver damage. Considering the likely involvement of the immune system in AH, and the frequent use of Lewis rats in autoimmune disease models, Lewis rats were examined in the model to determine whether they would more closely mimic the immune status of a chronic alcoholic and be a preferable strain for use in future experiments. Lipopolysaccharide-induced hepatic tumor necrosis factor-alpha, interleukin-1alpha, interleukin-1beta, and interleukin-6 mRNA expression was examined in both rat strains. The overall pattern of histological (panlobular piecemeal necrosis) and biochemical liver damage (plasma ALT levels), and cytokine expression was similar in both strains. Thus, it would appear that, despite the known susceptibility of Lewis rats to autoimmune phenomena, they do not respond to the experimental regime significantly better than Wistar rats. This study confirms that unknown mediators are contributing to the liver damage seen in this model and possibly in AH.
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PMID:A comparison of lipopolysaccharide-induced hepatitis in ethanol-fed Wistar and Lewis rats. 980 38

Hepatitis B virus (HBV) gene expression is downregulated in the liver of HBV transgenic mice by a posttranscriptional mechanism that is triggered by the local production of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) during intrahepatic inflammation (hepatitis). The molecular basis for this antiviral effect is unknown. In this study, we identified three HBV RNA-binding liver nuclear proteins (p45, p39, and p26) the relative abundance of which correlates with the abundance of HBV RNA in response to the induction of IFN-gamma and TNF-alpha. All three proteins bind to a 91-bp element located at the 5' end of a previously defined posttranscriptional regulatory element that is thought to mediate the nuclear export of HBV RNA. The presence of p45 correlates directly with the presence of HBV RNA, being detectable under baseline conditions when the viral RNA is abundant and undetectable when the viral RNA disappears in response to IFN-gamma and TNF-alpha. In contrast, p26 is inversely related to HBV RNA, being detectable only when the viral RNA disappears following cytokine activation. Finally, p39 is constitutively expressed, and its abundance and mobility appear to be slightly increased by cytokine activation. These results suggest a model in which hepatocellular HBV RNA content might be controlled by the stabilizing and/or destabilizing influences of these RNA-binding proteins whose activity is regulated by cytokine-induced signaling pathways.
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PMID:Hepatitis B virus RNA-binding proteins associated with cytokine-induced clearance of viral RNA from the liver of transgenic mice. 984 53

Cell-mediated immune responses to hepatitis B (HBV) and hepatitis C virus (HCV) antigens are vigorous and multispecific in acute, self-limited infections. Moreover, the prevalent cytokine pattern of circulating virus-specific T cells from patients who recover spontaneously from acute hepatitis is Th1-like. Longitudinal analysis of the T cell response to HCV antigens from the early stages of HCV infection in patients who recover from hepatitis and those who do not indicates that weaker responses and a prevalent Th2 pattern of cytokine production is associated with viral persistence and chronic evolution of disease. Although similar sequential studies are missing in hepatitis B, the observation that HBV-specific T cell responses are very weak or totally undetectable in the peripheral blood of patients with long-lasting chronic hepatitis B suggests that strength and quality of virus-specific T cell responses at the early stages of infection may influence the final outcome of both hepatitis B and C. While T cell hyporesponsiveness seems to be an important determinant for HBV persistence once chronic hepatitis has developed, this mechanism appears to be less critical in chronic HCV infection, because the vigor and quality of HCV-specific T cell responses seem to improve as a function of the duration of infection. This is shown by the finding that HCV-specific CD4- and CD8-mediated responses are easily detectable in the peripheral blood of patients with long-lasting chronic hepatitis C and that production of Th1 cytokines predominates within their livers. HCV therefore seems to be able to persist even in the face of an active T cell response and to acquire the capacity to survive within a host environment apparently unfavorable to its persistence. The high variability of HCV may explain its efficiency in escaping immune surveillance.
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PMID:Antiviral cell-mediated immune responses during hepatitis B and hepatitis C virus infections. 1002 13

The relationship between aplastic anemia and viral hepatitis is well recognized, and such patients usually have a high mortality. We successfully treated a case of aplastic anemia following living-related orthotopic liver transplantation (LROLT) for non-A, non-B, non-C hepatitis. A 2-yr-old boy with fulminant hepatic failure from non-A, non-B, non-C hepatitis received LROLT. Before transplantation, he had pancytopenia which was probably hepatitis associated, and viral suppression was suspected after bone marrow (BM) biopsy. After the transplantation, he developed progressive pancytopenia and a diagnosis of aplastic anemia was made via BM biopsy. With immunosuppressant agents (cyclosporine, methylprednisolone), cytokine therapy (granulocyte-colony stimulating factor (G-CSF), macrophage-colony stimulating factor (M-CSF), recombinant human erythropoietin (rhEPO)) was effectual and the patient recovered from pancytopenia. He was discharged from the hospital 57 d after the liver transplantation and remains well 1 yr after LROLT. Combined cytokine therapy with high doses of G-CSF, M-CSF and rhEPO appeared to be effective in the treatment of aplastic anemia following liver transplantation for non-A, non-B, non-C hepatitis. Since M-CSF activates macrophages, it may have contributed to the graft rejection. Careful consideration should be given to the use of high-dose M-CSF in liver transplant patients.
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PMID:Successful cytokine treatment of aplastic anemia following living-related orthotopic liver transplantation for non-A, non-B, non-C hepatitis. 1008 39

Toxoplasmosis has gained particular attention in the AIDS era as the most common opportunistic encephalitis in HIV-infected patients. Since there are important parallels between the human and rodent infection, experimental murine toxoplasmosis is widely used to study the immune reactions to this protozoal parasite. Oral application of low-virulent Toxoplasma (T.) gondii cysts leads to a biphasic disease characterized by an acute, generalized phase followed by a chronic stage confined to the brain, where an encephalitis with persistence of the parasite develops. Immunity to T. gondii is T cell mediated, and there is increasing evidence for a critical role of cytokines for an effective immune response. In order to address the functional role of interferon (IFN)-gamma in toxoplasmosis, we took advantage of mice lacking the IFN-gamma-receptor. Inactivation of the IFN-gamma-receptor rendered mice highly susceptible to T. gondii, and they died of a fulminant acute toxoplasmosis. Among the various organs affected, hepatitis was severe enough to cause death. In contrast to wild type animals, IFN-gamma-receptor-deficient mice were unable to activate their macrophages as evidenced by a lack of major histocompatibility complex (MHC) class II antigen induction and the absence of an upregulation of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS) mRNA transcripts, two macrophage effector molecules. These observations prompted the investigation of TNF- and TNF-receptor-mediated effects in toxoplasmosis by use of mice deficient in either the TNF-receptor type 1 (TNFR1) and/or the TNF-receptor type 2 (TNFR2). The lethal outcome of T. gondii-infected TNFR1/2- and TNFR1-deficient mice, but not of TNFR2-deficient and wild type animals, illustrated the important role of TNF-alpha and TNFR1-mediated signalling, respectively, in this infection. Histopathology attributed death of TNFR1- and TNFR1/2-deficient mice to a severe, necrotizing encephalitis. Unrestricted intracerebral parasite replication in these strains was associated with reduced numbers of iNOS+ leukocytes and a lack of iNOS mRNA induction in their brains as compared to resistant wild type and TNFR2-deficient mice. To precisely identify the cellular sources of cytokines in the brain, flow cytometry of leukocytes isolated from the brain, in situ hybridization, immunohistochemistry and RT-PCR analysis of cytokine mRNA transcripts of magnetically purified leukocyte populations were performed. These studies disclosed that both CD4+, CD8+ T lymphocytes and macrophages recruited to the brain as well as resident cell populations of the CNS including neurons, astrocytes and microglia contributed to the intracerebral cytokine synthesis. Each population was characterized by a specific cytokine pattern. Interestingly, activation of brain cells is a hallmark of Toxoplasma encephalitis. The marked induction of a variety of immunologically important cell surface molecules as MHC class I and II antigens, cell adhesion molecules and their ligands on microglia points to a particular important role of this cell type for the immune response to T. gondii, since the expression of these molecules is a prerequisite for cellular interactions with T cells. The observation of a prominent interleukin (IL)-10 production in the T. gondii-infected brain initiated studies addressing the function of this powerful immunosuppressive mediator in chronic Toxoplasma encephalitis. Neutralization experiments revealed that IL-10 facilitates persistence of the parasite in the brain by downregulating the intracerebral immune response. On the other hand, IL-10 may exert a regulatory role and may be necessary to prevent immunopathological effects of an uncontrolled immune response. In conclusion, these studies demonstrate the important role of the cytokines IFN-gamma and TNF-alpha and their receptors, respectively, for an effective control of T. gondii. In the CNS, the target organ of the parasite, a
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PMID:[Rudolf-Virchow Prize 1998. Award lecture. Toxoplasmosis: a model infection for studying systemic and intracerebral immune reactions]. 1009 13


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