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)

The content of cytokines of type Tx1 (IL-2 and IFN-gamma) and type Tx2 (IL-4) in blood sera of 132 patients with hepatitis C and the combined form of hepatitis B + C was studied. For control, blood sera taken from healthy donors were used. A significant increase, in comparison with the control, in the content of IL-4 in all subgroups of the patients was registered. The content of IFN-gamma reached the maximum level in patients with acute hepatitis C with the positive result of the polymerase chain reaction (PCR) for the virus (216.4 and 46.4 pg/ml respectively) and was somewhat lower in acute hepatitis C with the negative PCR-result (77.7 and 9.6 pg/ml), mean while in the chronic course of hepatitis C these data were within the limits of control values irrespective of the results of PCR. In case of mixed infection in the acute clinical form a significant increase in the concentration of IFN-gamma (34.4 pg/ml) in comparison with the control (25.3 pg/ml) was observed. The content of IFN-gamma in patients with acute hepatitis C and the positive result of the test for NS antibodies also reached the maximum level (207.3 and 42.7 pg/mg respectively). But in contrast to hepatitis C in the acute form with the negative results of PCR in patients with hepatitis C in the acute form and the negative results of the NS test these data were within the limits of control values, as well as in the chronic course of hepatitis C irrespective of the results of the NS antibodies serum test. In case of mixed infection a significant increase in the concentration of IFN-gamma was registered in the subgroup of patients with the acute form of NS+ (39.9 pg/ml). The data obtained in this study were indicative of significant changes in the serum profile of serum cytokines of types Tx1 and Tx2 in different forms and courses of virus hepatitis. This makes it possible to believe that the chronization of the process was associated with the prevalence of the Tx2 function.
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PMID:[Level of Tx1- and Tx2-type cytokines in blood sera of hepatitis C patients]. 1123 7

Administration of Con A induces severe injury to hepatocytes in mice and is considered to be a model for human hepatitis. In the current study, we investigated the role of CD44 in Con A-induced hepatitis. Intravenous administration of Con A (20 mg/kg) caused 100% mortality in C57BL/6 CD44-knockout (KO) mice, although it was not lethal in C57BL/6 CD44 wild-type (WT) mice. Administration of lower doses of Con A (12 mg/kg body weight) into CD44 WT mice induced hepatitis as evident from increased plasma aspartate aminotransferase levels accompanied by active infiltration of mononuclear cells and neutrophils, and significant induction of apoptosis in the liver. Interestingly, CD44 KO mice injected with similar doses of Con A exhibited more severe acute suppurative hepatitis. Transfer of spleen cells from Con A-injected CD44 KO mice into CD44 WT mice induced higher levels of hepatitis when compared with transfer of similar cells from CD44 WT mice into CD44 WT mice. The increased hepatitis seen in CD44 KO mice was accompanied by increased production of cytokines such as TNF-alpha, IL-2 and IFN-gamma, but not Fas or Fas ligand. The increased susceptibility of CD44 KO mice to hepatitis correlated with the observation that T cells from CD44 KO mice were more resistant to activation-induced cell death when compared with the CD44 WT mice. Together, these data demonstrate that activated T cells use CD44 to undergo apoptosis, and dysregulation in this pathway could lead to increased pathogenesis in a number of diseases, including hepatitis.
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PMID:CD44-deficient mice exhibit enhanced hepatitis after concanavalin A injection: evidence for involvement of CD44 in activation-induced cell death. 1134 3

Real-time polymerase chain reaction (PCR) assays were developed for woodchuck leukocyte cluster of differentiation (CD) and cytokine mRNA expression. Plasmid DNA standards of each marker (CD3, CD4, CD8, IL-2, IFN-gamma, TNF-alpha, IL-4, IL-10), and RNA standards from mitogen-stimulated woodchuck peripheral blood mononuclear cells (PBMCs) were used to validate and optimize the assays for TaqMan 7700 and iCycler PCR instruments. The complementary DNAs (cDNAs) produced by reverse transcription (RT) of RNA were quantified by real-time PCR against the plasmid DNA standards (6-8 log range) with detection of as few as 10-50 copies of amplicon cDNA per reaction. Analysis of unstimulated and concanavalin A-stimulated woodchuck PBMC demonstrated increased CD and cytokine mRNA expression following mitogenic activation. A liver sample from a woodchuck hepatitis virus (WHV) infected woodchuck with histologically confirmed acute hepatitis had increased intrahepatic CD and cytokine mRNAs compared to liver from an uninfected control woodchuck. The real-time PCR assays were highly specific for the woodchuck markers in PBMC and liver samples and were equally applicable for use in alternate real-time PCR instrumentation. These assays will enable the high-throughput analyses of mRNA markers during WHV infection, and thereby facilitate continued modelling of the immunopathogenesis and immunotherapy of human hepatitis B virus (HBV) infection.
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PMID:Real-time polymerase chain reaction assays for leukocyte CD and cytokine mRNAs of the Eastern woodchuck (Marmota monax). 1205 47

The activation of T-cells and macrophages and subsequent induction of cytokines are critical factors in the development of hepatitis. Up-regulation of pro-inflammatory cytokines, e.g. TNF has been shown to induce liver injury while counter regulation by anti-inflammatory cytokines, e.g. IL-10 is protective. We compared the induction of liver injury and the expression pattern of a variety of cytokines in T-cell- versus non-T-cell-dependent mouse models of liver injury. TNF, IFNgamma, IL-2, IL-4, IL-6, IL-10 and IL-12 were measured in plasma and liver tissue after either Concanavalin A (Con A), D-galactosamine/lipopolysaccharide (GalN/LPS) or high dose LPS induced liver injury. Additionally, the intra-hepatic expression of the putative pathogenicity factor high mobility group 1 protein (HMG-1) was compared in all three models.
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PMID:Cytokine expression in three mouse models of experimental hepatitis. 1224 77

Although several mouse models of AIH have been described, no model is ideal. Indeed, the disease is self-limited in each model, and none is associated with significant liver fibrosis or progression to cirrhosis. Nevertheless, these models should be useful for testing different hypotheses regarding the initiation of AIH. Still, each model poses unique limitations. The EAIH model initiated by immunization with crude liver antigens in CFA has been plagued by a high prevalence of hepatitis lesions in CFA controls and inconsistencies in results. The TGF beta-1 and IL-2 deficient models lead to high in utero mortality and short median life spans in the surviving animals. Lastly, all models require more detailed characterization of the antigen specificity of infiltrating liver T cells and the pathogenesis of liver cell injury.
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PMID:Animal models of autoimmunity. 1236 80

We have previously reported several CTL epitopes derived from the hepatitis B viral X Ag (HBx). In this study, we evaluated whether HBx-specific CTLs can be effectively used in adoptive cancer immunotherapy. To validate the possibility, four peptides containing a HLA-A2.1-restricted binding consensus motif were identified from the HBx protein and tested for their ability to activate CTL from PBMCs isolated from chronic carriers of HBV (n = 12). We selected two highly potent epitopes, HBx 52-60 (HLSLRGLFV) and HBx 115-123 (CLFKDWEEL), that are capable of inducing Ag-specific cytotoxic T cells in patient PBMCs. For adoptive immunotherapy using HBx-specific CTLs, we generated CTL clones restricted to the HBx 52-60 or HBx 115-123 peptide using a limiting dilution technique. LC-46, an HBx 52-60-specific clone, is CD62L(-)CD69(+)CD45RO(+)CD45RA(-)CD25(dim) and is stained by IFN-gamma (approximately 92%), IL-2 (30%), and TNF-alpha (56%), but not by IL-5, IL-10, IL-12, or TNF-beta, indicating that the cells are fully activated T cytotoxic 1-type cells. When LC-46 cells were adoptively transferred into xenografted nude mice bearing human hepatomas expressing HLA-A2.1 molecules and intracellular HBx proteins, the tumors were eradicated. Taken together, our data provide solid evidence for the feasibility of adoptive immunotherapy with HBx-sensitized CTLs in hepatitis disease, including hepatocellular carcinoma (HCC).
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PMID:Tumor eradication by hepatitis B virus X antigen-specific CD8+ T cells in xenografted nude mice. 1253 74

An experimental model of the viral C-hepatitis (VCH) infection was worked out in vitro and it was found suitable to study the influence of interferon (IFN) preparations produced on the infection caused by an HCV cytopathogenic variations, i.e. the SW-13 human adrenocarcinoma cellular culture sensitive to the anti-VCH action of alpha-IFN and the MT-4 human lymphoblastoid cellular culture non-sensitive to the anti-VCH action of alpha-IFN. The above cellular models were employed to study, by using the methods of reverse transcription and polymerize chain reaction (RT-PCR), the influence produced by alpha-IFN on the VCH infectious activity as well as to study the changes in the activity of the below cytokine mRNAs: alpha-IFN, gamma-IFN, IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18 and TNF-alpha. A double treatment of the SW-13 alpha-IFN cellular cultures 24 and 48 hours after the infection was found to essentially suppress (by 4 Ig) reproduction of the VCH cytopathogenic variant. It was detected that the VCH reproduction is mediated by the regulation of a number of cytokine genes. The study results can be a basis for a more effective use of the alpha-IFN preparations in the therapy of VCH-infections.
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PMID:[Antiviral effect of alpha-interferon and cytokine mRNA level in cell cultures infected with a cytopathogenic variant of the hepatitis C virus]. 1260 58

Immune response messenger RNAs (mRNA) were compared in liver during self-limited (resolved) and chronic neonatal woodchuck hepatitis virus (WHV) infection. At week 14 postinfection (mid-acute phase), mRNAs for leukocyte markers (CD3, CD4, CD8), type 1 cytokines and related transcription factors (IFN-gamma, TNF-alpha, STAT4, T-bet), and IL-10 were increased in livers from resolving infections, but mRNAs of other type 1 (IL-2) and type 2 (IL-4, STAT6, and GATA3 markers remained at baseline levels. Increased coexpression of IFN-gamma and TNF-alpha mRNAs correlated in most cases with lower levels of intrahepatic WHV covalently closed circular DNA (cccDNA). At the same time point postinfection, livers from woodchucks that eventually progressed to chronic infection had baseline or slightly elevated levels of CD and type 1 mRNAs, which were significantly lower (or elevated less frequently) compared with resolving woodchucks. Earlier, at week 8, there were no differences between the two outcome settings. During these early time points and at a later stage in chronic infection (15 months), type 2 mRNAs in carrier liver remained at baseline levels or, when elevated, were never in excess of those in resolving woodchucks. In conclusion, the onset and maintenance of neonatal chronic WHV infection are not associated with antagonistic type 2 immunoregulation of type 1 responses in liver. Accordingly, chronicity develops in association with a primary deficiency in the intrahepatic CD responses, especially involving CD8(+) T lymphocytes, and in both extracellular (cytokine) and intracellular (transcriptional) type 1 response mediators. This has relevant implications for future treatment of chronic hepatitis B virus (HBV) infection in humans.
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PMID:Role of type 1 versus type 2 immune responses in liver during the onset of chronic woodchuck hepatitis virus infection. 1266 69

Chronic hepatitis B virus (HBV) infection can cause a broad spectrum diseases, including from asymptomatic HBV carriers or cryptic hepatitis, to acute hepatitis, chronic hepatitis, Liver cirrhosis and primary hepatocellular carcinoma. The variable pattern and clinical outcome of the infection were mainly determined by virological itself factors, host immunological factors and genetic factors as well as the experimental factors. Among the human genetic factors, major candidate or identified genes involved in the process of HBV infection fall into the following categories: (1) genes that mediate the processes of viral entry into hepatocytes, including genes involved in viral binding, fusion with cellular membrane and transportation in target cells; (2) genes that modulate or control the immune response to HBV infection; (3) genes that participate in the pathological alterations in liver tissue; (4) genes involved in the development of liver cirrhosis and hepatocellular carcinoma associated with chronic HBV infection, including genes related to mother-to-infant transmission of HBV infection; and (5) those that contribute to resistance to antiviral therapies. Most of the reports of human genes associated with HBV infection have currently focused on HLA associations. For example, some investigators reported the association of the HLA class II alleles such as DRB1*1302 or HLA-DR13 or DQA1*0501-DQB1*0301-DQB1*1102 haplotypes with acute and/or chronic hepatitis B virus infection, respectively. Several pro-inflammatory cytokines such as Th1 cytokines (including IL-2 and IFN-gamma) and TNF-alpha have been identified to participate the process of viral clearance and host immune response to HBV. In contrast, the Th2 cytokine IL-10 serves as a potent inhibitor of Th1 effector cells in HBV diseases. The MBP polymorphisms in its encoding region were found to be involved in chronic infection. Thus, reports from various laboratories have shown some inconsistencies with regard to the effects of host genetic factors on HBV clearance and persistence. Since genetic interactions are complex, it is unlikely that a single allelic variant is responsible for HBV resistance or susceptibility. However, the collective influence of several single nucleotide polymorphisms (SNPs) or haplotype (s) may underlie the natural combinational or synergistic protection against HBV. The future study including the multi-cohort collaboration will be needed to clarify these preliminary associations and identify other potential candidate genes. The ongoing study of the distributions and functions of the implicated allele polymorphisms will not only provide insight into the pathogenesis of HBV infection, but may also provide a novel rationale for new methods of diagnosis and therapeutic strategies.
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PMID:Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection. 1267 1

In the presented studies HBcAg-specific cytokine production (IFN-gamma, IL-2, IL-4, IL-5 and IL-10) was evaluated, by Th lymphocytes isolated from peripheral blood of children with acute or chronic B hepatitis. Moreover, effect of IL-10 neutralization was examined on HBcAg-induced secretory response of Th lymphocytes obtained from children with chronic B hepatitis. The studies were performed on 12 children with acute self-limited B hepatitis and 20 children with chronic active B hepatitis. CD4 T cells were isolated from peripheral blood of the patients, cultured for 48h in presence of rHBcAg or in its absence (control). Production of studied cytokines was monitored using ELISPOT and ELISE assays. The course of acute self-limited B hepatitis was associated with preferential Th1-type response, manifested by elevated production of IFN-gamma and IL-2. On the other hand, in chronic B hepatitis a diminished response to HBcAg of both Th1 and Th2 types was disclosed, characterized by very low secretion of IFN-gamma, IL-2, IL-4 and IL-5. In parallel, preferential antigen-specific production of IL-10 was noted and its suppressive effect on HBcAg-induced response of Th1 cells. The results permitted to conclude that in children with acute self-limited B hepatitis preferential HBcAg-specific activation of Th1 lymphocytes may be of significance for efficient anti-HBV immune response. On the other hand, development of chronic B infection in children seems to be determined by disturbed HBcAg-specific functions of both Th1 and Th2 cells whereas activity of the disease may be controlled by anti-inflammatory response of antigen-presenting cells and/or of regulatory CD4 T lymphocytes, involving IL-10 production.
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PMID:HBcAg-specific cytokine production by CD4 T lymphocytes of children with acute and chronic hepatitis B. 1460 4


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