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)

Cytokines released by infiltrating T cells may contribute to the hepatic injury in chronic hepatitis. Therefore, we characterized peripheral blood- and liver-infiltrating T cells from patients with chronic hepatitis of different etiology and determined the T cell phenotypes and the cytokine release. Liver tissue and peripheral blood-derived T cells from patients with autoimmune hepatitis and primary biliary cirrhosis predominantly expressed CD4-molecules and the alpha- and beta-chains of the T cell receptor (TCR). In chronic viral hepatitis B and C, liver- and blood-derived T cells were preferentially CD8+ T cells expressing the alpha beta TCR. Mitogenic stimulation with irradiated Daudi lymphoma cells and phytohemagglutinin led to a strong release of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) by T cells in patients with chronic hepatitis and in healthy controls. T cells from patients with primary biliary cirrhosis and some patients with autoimmune hepatitis showed a significantly higher secretion of interleukin-4 (IL-4) and interleukin-10 (IL-10) than T cells from patients with chronic viral hepatitis or healthy controls. Histologic inflammatory activity did not correlate with the amount of cytokines released after mitogenic activation. In conclusion, liver tissue and peripheral blood T cells of patients with autoimmune hepatitis and primary biliary cirrhosis were dominated by CD4+ TCR alpha beta+ T helper/inducer cells, whereas in chronic viral hepatitis an enrichment of CD8+ TCR alpha beta + cytotoxic/suppressor T cells was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T lymphocytes from patients with chronic hepatitis of different etiology. 807 96

Rolipram is a type IV phosphodiesterase inhibitor endowed with powerful immunomodulatory properties. In this study, we evaluated the effects of this drug on the development of the T-cell-mediated hepatitis inducible in mice by concanavalin A. The results indicated that prophylactic treatment with either 5 or 10 mg/kg rolipram injected intraperitoneally 24 h and 1 h prior to intravenous (i.v.) challenge with 20 mg/kg concanavalin A successfully ameliorated serological and histological signs of liver damage, so that the treated mice showed lower transaminase levels in the plasma and milder mononuclear cell infiltration of the liver as compared to vehicle-treated controls. Moreover, this effect was associated with profound modifications of circulating levels of cytokines released after concanavalin A injection, with the blood levels of interferon-gamma and tumor necrosis factor-alpha being significantly lower and those of interleukin-10 higher than those of the control mice. In particular, the increased blood levels of interleukin-10 might play an important role in the anti-hepatitic effects of rolipram as coadministering this compound with anti-interleukin-10 monoclonal antibody significantly reduced its anti-inflammatory action. These results suggest that rolipram may be useful in the clinical setting for the treatment of cell-mediated immunoinflammatory diseases such as immunoinflammatory hepatitis.
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PMID:Prevention by rolipram of concanavalin A-induced T-cell-dependent hepatitis in mice. 1007 16

Genetic involvement in type 1 autoimmune hepatitis (AIH) is indicated by a marked female preponderance and strong, well-established, human leukocyte antigen (HLA) associations. These associations, however, are not universal and a number of genes outside the major histocompatibility complex may also play a role in susceptibility to type 1 AIH. Prime candidates at present are those polymorphic genes encoding the proinflammatory and immunoregulatory cytokines. The aim of this study was to investigate, for the first time, 2 members of the interleukin-1 (IL-1) family (IL-1B and IL-1RN), 3 polymorphic sites in the interleukin-10 (IL-10) gene promoter (positions -1082, -819, and -592), and 2 polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) promoter (positions -308 and -238) in type 1 AIH. The study was performed on 2 independently collected DNA banks, each with appropriate controls, and throughout the analysis associations described in the first set were confirmed in the second set. Standard polymerase chain reaction (PCR)-based genotyping techniques were used. Overall there were no significant differences in the distributions of the IL-1B and IL-10 alleles, genotypes, or haplotypes in either study set. In contrast we report a significant association between type 1 AIH and TNF*2 (first set: 34% of controls vs. 49% of patients, Pc =.014 and second set: 26% vs. 56%, P =.00008). However, TNF*2 is found in strong linkage disequilibrium with the HLA A1-B8-DR3 haplotype and stratification analysis indicates that the association with TNF*2 is interdependent with HLA DRB1*0301. This is an indication that there is more than one susceptibility allele for type 1 AIH on chromosome 6p21.3.
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PMID:Frequency and nature of cytokine gene polymorphisms in type 1 autoimmune hepatitis. 1049 33

To assess the relationship between serum cytokine behavior and treatment outcome in type 1 autoimmune hepatitis, serum levels of interferon-gamma, interleukin-2, interleukin-4, and interleukin-10 were measured by enzyme immunoassay in 43 patients and 20 normal subjects. Serum samples were similarly tested in 38 patients after corticosteroid treatment. Serum levels of interleukin-2 and interleukin-4 were significantly lower in patients than in normal subjects. Interleukin-2 was the least common cytokine detected before (3%), during (0%), or after treatment (0%). Serum levels of interleukin-10 at presentation did not differ from those of normal subjects but they did decrease during therapy, especially in patients who entered remission. Changes in these levels, however, did not always parallel treatment outcome or histological activity. We conclude that serum levels of interleukin-2 and interleukin-4 are lower than normal in type 1 autoimmune hepatitis. Serum concentrations of interleukin-10 diminish during corticosteroid therapy but changes do not closely reflect outcome. The rarity of interleukin-2 in serum may be a distinguishing feature.
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PMID:Nature and behavior of serum cytokines in type 1 autoimmune hepatitis. 1079 72

Helicobacter hepaticus has been reported to induce colitis, hepatitis, and hepatocellular carcinoma in several different murine models. The aim of this study was to determine if H. hepaticus will cause colitis in monoassociated mice lacking the interleukin-10 gene (IL-10(-/-) mice) and potentiate colitis in specific-pathogen-free (SPF) IL-10(-/-) mice. Germfree IL-10(-/-) mice on either a mixed (C57BL/6 x 129/Ola) or inbred (129/SvEv) genetic background were monoassociated with H. hepaticus ATCC 51448 by oral feeding and rectal enemas. In a second experiment, germfree IL-10(-/-) mice were colonized with stool from SPF mice that harbored or did not harbor endogenous H. hepaticus. After 7 to 9 weeks of colonization, weight loss and mortality were assessed, the colon was isolated for histology and IL-12 secretion, and mesenteric lymph node cells were assessed for T-cell activation markers. It was found that IL-10(-/-) mice monoassociated with H. hepaticus for up to 16 weeks showed almost no histologic colitis or increased IL-12 production. SPF IL-10-knockout mice had no significant difference in weight loss, mortality rate, histologic scores, colonic IL-12 secretion, or T-cell activation with or without H. hepaticus. We conclude that H. hepaticus does not induce or potentiate disease in our IL-10(-/-) mice and therefore is not required to induce colitis in genetically susceptible hosts.
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PMID:Helicobacter hepaticus does not induce or potentiate colitis in interleukin-10-deficient mice. 1094 32

A mechanism of liver injury such as, viral hepatitis or autoimmune hepatitis is considered to involve the impairment of hepatocytes mainly mediated by T-cell immunity, but the roles of a variety of cytokines involved in regulation remain unclarified. We investigated the involvement of various cytokines, particularly, interleukin-10 (IL-10) which is considered to be an anti-inflammatory cytokine, in a murine model of experimental liver injury induced by Concanavalin A (Con A). The model of liver injury was made by intravenous injection of Con A (0.5 &mgr;g) through the caudal vein in 6-week-old female BALB/c mice weighting 20 g. By collecting blood before and at 1, 3, 6, 12 and 24 h after the injection of Con A, alanine aminotransferase (ALT) levels were sequentially measured, and liver tissue was sampled to examine liver injury. Furthermore, TNF-alpha, IL-4 and IL-10 levels were sequentially determined by enzyme-linked immunosorbent assay (ELISA). Serum ALT significantly increased between 3 and 24 h after the Con A injection, and spotty necrosis was histologically observed, suggesting mild liver injury. TNF-alpha and IL-4 increased soon after the injection of Con A. IL-10 increased bimodally soon after and at 12 h after the Con A injection. After neutralizing antibodies (1 &mgr;g) to IL-10 were intraperitoneally injected into the same model at 6 h before Con A treatment, serum ALT levels and the histology of the liver were examined 12 h after the Con A injection. ALT was significantly higher in the group treated with anti-IL-10 antibody (130.7+/-33.5 IU per I) than in the non-treated group (56.5+/-3.5 IU per I) (P<0.05). Histological examination showed spotty necrosis in the group treated with anti-IL-10 antibody. These results suggest that IL-10 has inhibitory effect on liver injury in a murine model of Con A-induced experimental liver injury mediated by cellular immunity.
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PMID:Involvement of IL-10, an anti-inflammatory cytokine in murine liver injury induced by Concanavalin A. 1134 58

Antigen presenting cells, especially the antigen presenting dendritic cells (DC) in the tissue, regulate the magnitude of antigen-specific immune response. A role of impaired and narrowly focused specific immune response has been implicated in the pathogenesis of chronic hepatitis due to hepatitis B virus and hepatitis C virus. In order to clarify this role, we studied liver DC from interferon gamma (IFN-gamma) transgenic mouse (TgM), an animal model of chronic hepatitis. These mice had high serum levels of alanine transaminase and histological evidence of chronic hepatitis. Transgene negative offspring (littermate control) with normal serum transaminase levels and without any evidence of hepatitis were used as controls. The stimulatory capacity of the liver DC from IFN-gamma TgM in allogenic mixed leukocyte reaction was significantly lower than that of the liver DC from control mouse. The endocytosis capacity was significantly lower in liver DC from IFN-gamma TgM than in that from the control mouse. Most importantly, liver DC from IFN-gamma TgM were unable to induce antigen-specific proliferation. The impaired function of liver DC from these mice may be attributable to increased production or induction of suppressor cytokines such as interleukin-10 and nitric oxide. Defective capacity of liver DC from mouse with chronic hepatitis (IFN-gamma TgM) may be related to impaired magnitude of specific immune response in the liver.
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PMID:Loss of immunogenecity of liver dendritic cells from mouse with chronic hepatitis. 1174

The interleukin-12(IL-12), interleukin-10(IL-10), tumor necrosis factor(TNF) and nitric oxide (NO) levels in serum of 90 patients with hepatitis and cirrhosis were measured by the method of ELISA and colorimeter. The levels of IL-12, IL-10 and NO in serum of the patients with hepatitis were in close proximity to the level of healthy control, but the TNF level was significantly higher than that of healthy control. The IL-12, IL-10, TNF and NO levels in serum of the patients of hepatic cirrhosis were significantly higher than that of healthy control and patients with hepatitis. The results suggested that the NO level was not related with the hepatic damage of acute hepatitis. The dysfunction of immunology in the patients with cirrhosis was related with the increase of NO level.
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PMID:[Relationship of nitric oxide and immunal function of the patients with acute hepatitis and hepatic cirrhosis]. 1208 Jun 55

Inflammation is commonly observed in liver diseases and is frequently complicated by fibrosis and cirrhosis in end-stage disease. The only curative treatment for cirrhotic patients is liver transplantation. However, organ shortage as well as an increasing organ demand call for early treatment of liver disease and prevention of fibrosis. Experimental data have shown the critical role of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the development of liver injury. Here, we review our work on the role of endogenously produced interleukin-10 (IL-10), a potent anti-inflammatory cytokine, in several experimental models of acute and chronic liver injury. First, in acute macrophage-mediated hepatitis induced by galactosamine/lipopolysaccharide administration, IL-10 neutralisation led to a more severe liver damage, whereas IL-10 injection, even delayed, was able to limit liver necrosis. A similar protective effect of IL-10 was observed in acute T cell-mediated hepatitis induced by concanavalin A (Con A) injection. The immunoregulatory role of IL-10 was then established after repeated exposition to Con A. In carbon tetrachloride liver injury, two other properties of IL-10 have been suggested: modulation of hepatocyte proliferation and modulation of liver fibrosis. Finally, the potential therapeutic applications in human liver disease as well as the potential side effects are discussed.
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PMID:Modulation of liver injury by interleukin-10. 1281 43

We have recently reported differences in the hematopoiesis between autoimmune hepatitis type 1 (AIH-1) and primary biliary cirrhosis (PBC). In view of the notion that cytokines are regulators of hematopoiesis, we investigated in our tertiary center the cytokine production in the bone marrow (BM) of the same consecutive cohort of patients (13 AIH-1, 13 PBC, 10 healthy and 7 patients with cirrhosis due to chronic hepatitis B). Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) were determined in the supernatants of long-term BM cultures by ELISAs. IL-4, TNF-alpha and TGF-beta were found significantly increased in the BM of PBC patients compared to AIH-1 and both control groups. AIH-1 patients had significantly higher BM IL-10 compared to PBC patients and higher IL-10, IL-4 and TNF-alpha compared to controls. BM IFN-gamma was significantly higher in PBC and AIH-1 patients compared to controls. In AIH-1 patients, IL-10 was positively correlated with CD34+, CD34+/CD38- and CD34+/CD38+ cell proportions. In conclusion, the BM cytokine microenvironment of PBC and AIH-1 patients differs significantly compared to that of healthy individuals and cirrhotic patients of non-autoimmune etiology. Differences were also found between patients with PBC and AH-1. The implication of BM in the pathogenesis of autoimmune liver diseases is possible and needs further investigation.
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PMID:Autoimmune hepatitis type 1 and primary biliary cirrhosis have distinct bone marrow cytokine production. 1624 12


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