Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-gamma (IFN-gamma) appears to be important for the activation of T cells, and its binding to IFN-gamma receptors on T cells is an essential step for its actions. We investigated the expression of IFN-gamma receptors on T cells in chronic liver disease using radioiodinated recombinant interferon-gamma binding assay, and by Scatchard analysis. The mean numbers of IFN-gamma receptors on T cells from controls, asymptomatic hepatitis B virus carriers (ASC), patients with chronic active hepatitis (CAH), and patients with liver cirrhosis (LC) were 2,205 +/- 497, 2,494 +/- 1,074, 1,925 +/- 735, and 1,666 +/- 653, respectively. The numbers of IFN-gamma receptors on T cells from the patients with LC were significantly smaller than those of controls (P less than 0.05). Kids of IFN-gamma receptor on T cells from control and patient groups were 2.3 4.8 x 10(-9) M, and there was no significant difference among the groups. The percentage of T cells reactive with OKT3, OKT4, or OKT8 was similar in control and patient groups. These findings suggest that the decrease in IFN-gamma receptors in LC is not related to the activity of the liver damage, but is associated with the severity of the underlying disease. The normal expression of IFN-gamma receptors on T cells from CAH may provide a reasonable basis for IFN-gamma therapy to type B CAH.
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PMID:Interferon-gamma receptors on T cells in patients with chronic liver disease. 297 98

The effects of glycyrrhizin, a component of licorice (Glycyrrhiza glabra) roots, on the production of interferon-gamma in human peripheral lymphocyte-macrophage cultures by concanavalin A (Con A) was examined. Interferon-gamma production in normal lymphocyte-macrophage cultures treated with 10 to 100 micrograms/ml of glycyrrhizin at 37 degrees C for 12 hr or longer, and then treated with 10 micrograms/ml of Con A, was enhanced four to eight times compared to control cell cultures. Lymphocyte-macrophage cultures treated with 10 to 100 micrograms/ml of glycyrrhizin alone did not produce interferon. No significant difference in the adsorption of [3H]Con A to glycyrrhizin-treated and control lymphocyte-macrophage cultures was found, but RNA and protein synthesis of the treated lymphocytes was increased compared to control cells; DNA synthesis, however, was reduced. Collaboration between enriched T-lymphocytes and macrophages, both treated with glycyrrhizin, was needed for the enhancement of interferon-gamma production. A smaller increase in interferon production was also observed in the glycyrrhizin-treated peripheral lymphocyte-macrophage cultures derived from an asymptomatic carrier of hepatitis B virus, in response to Con A and surface antigen of hepatitis B virus.
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PMID:Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus. 308 Jul 54

We investigated the role of the interferon system in the pathogenesis of chronic liver disease. Interferon-gamma production by peripheral blood mononuclear cells was measured with an ELISA. While concanavalin A-stimulated and recombinant interleukin 2-stimulated production of interferon-gamma in patients with chronic active hepatitis and liver cirrhosis was significantly decreased when compared with that of controls (518 +/- 189 and 729 +/- 195 units per ml, mean +/- S.D.), there was also a lot of overlap. Addition of indomethacin to the cultures partially restored interferon-gamma production in patients with chronic active hepatitis and liver cirrhosis, indicating that suppressor function of monocytes was, in part, responsible for the diminished interferon-gamma production. Serial studies showed that interferon-gamma production rose during acute deterioration of illness, during treatment with interleukin 2 and with the improvement of clinical course. Interferon-gamma production was not different among hepatitis B e antigen or antibody positive, and non-A, non-B patients with chronic active hepatitis and liver cirrhosis. Our findings suggest that diminished interferon-gamma production is associated with disease severity in chronic liver disease, irrespective of the hepatitis B virus carrier state. It would be interesting to compare the efficacy of treatment with interferon-gamma or interferon-gamma inducers such as interleukin 2 in chronic hepatitis B patients with and without decreased in vitro interferon-gamma production.
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PMID:Interferon-gamma production by peripheral blood mononuclear cells of patients with chronic liver disease. 310 84

Eight mouse monoclonal antibodies specific for hepatitis B surface antigen (HBsAg) were examined for their effects on the antigen-induced proliferative response and lymphokine production of human HBsAg-specific T-cell clones in vitro. While all specifically enhanced the T-cell proliferative response, antibodies of the IgG class were generally more effective than those of the IgM class. Both the divalent F(ab')2 and the monovalent Fab fragments of an IgG monoclonal antibody had no effects, indicating that the Fc portion of the antibody molecules was required. Since antigen-presenting cells bear surface receptors for the Fc of IgGs and fewer or none for that of IgMs, the above results also suggest that antibodies enhance the capture of antigens by antigen-presenting cells as a result of the binding of antigen-antibody complexes to the Fc receptors on these cells. In addition to potentiating the proliferation of the T-cell clones, antibodies also increased the antigen-induced production of interferon-gamma by these cells. The present in vitro studies suggest that antibodies may regulate immune responses and do so by enhancing antigen presentation and thus augmenting antigen-induced activation and clonal expansion of T cells.
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PMID:Regulation of T-cell function by antibodies: enhancement of the response of human T-cell clones to hepatitis B surface antigen by antigen-specific monoclonal antibodies. 643 21

To investigate whether there is any evidence of an immune stimulation against hepatitis B virus surface antigen (HBsAg) in asymptomatic HBsAg carriers, proliferative and cytotoxic responses to HBsAg were measured in their peripheral blood lymphocytes. Although the majority of asymptomatic carriers had no proliferative response to HBsAg, 3 (25%) of 12 carriers showed significant T cell proliferation against HBsAg. In addition, using HBsAg-expressing autologous lymphoblastoid cell line (LCL) as target cells, HBsAg-specific cytotoxic activity was found in 2 of 3 asymptomatic HBsAg carriers who had a proliferative response against HBsAg. Furthermore, 6 cytotoxic T lymphocyte (CTL) clones were isolated from 1 asymptomatic carrier. The epitope recognized by 2 CTL clones was mapped to the major HBsAg residues 158-172. These CTL clones were able to produce interferon-gamma, tumor necrosis factor-alpha, or granulocyte-macrophage colony-stimulating factor. These findings demonstrate the presence of HBsAg-specific, major histocompatibility complex class I-restricted CTL in asymptomatic HBsAg carriers.
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PMID:Presence of hepatitis B surface antigen (HBsAg)-specific cytotoxic T cells in asymptomatic HBsAg carriers. 751 10

Natural interferon-gamma at a dose of 0.5 x 10(6) or 1 x 10(6) IU daily was intramuscularly administered daily for 4 weeks to 15 patients with chronic hepatitis B. The efficacy and safety of the treatment were evaluated for 24 weeks following the completion of the 4-week treatment period. Persistent disappearance of HBeAg was observed in 5 of 15 patients. Serum hepatitis B virus (HBV)-related DNA polymerase disappeared in 5 of 13 patients at the end of interferon therapy. On the other hand, serum ALT and beta 2-microglobulin levels showed a significant increase during the interferon therapy period. The side effects were completely reversible. These findings suggest that interferon-gamma has an antiviral effect in patients with chronic hepatitis B and that the main mechanism of the therapeutic effect may be associated with the elimination of HBV-infected hepatocytes due to the immunopotentiating effect of the substance.
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PMID:Clinical evaluation of intramuscular administration of natural interferon-gamma in the treatment of chronic hepatitis B. 759 91

To determine the relationship between hepatitis B virus (HBV) replication and HLA antigen display at a cellular level, the hepatic expression of HLA antigens and HBV genome (HBV-DNA)/gene products (HBsAg/HBcAg) was studied in 24 patients with chronic HBV infection using simultaneously immunohistochemistry and nonisotopic in situ hybridization. The effect of interferon-alpha and interferon-gamma on hepatocyte HLA antigen expression was also evaluated using primary hepatocyte culture in eight patients with chronic HBV infection. HLA class I antigens were detected on hepatocyte membrane in 23 patients (95.8%). Hepatocytes positive for HBcAg and HBV-DNA (cytoplasmic +/- nuclear) were either negative or only faintly positive for HLA class I antigens, while hepatocytes positive for HBsAg showed similar levels of HLA class I antigen expression compared with those hepatocytes with no HBsAg expression. In contrast, hepatocytes adjacent to inflammatory infiltrates, whether positive for HBV-DNA or HBV antigens or not, were always strongly positive for HLA class I antigens. Furthermore, active liver histology (N = 12) was associated with a higher overall level of hepatic HLA class I antigen expression as compared with inactive histology (N = 12, P = 0.003). Both interferon-alpha and interferon-gamma treatment in vitro enhanced hepatocyte HLA class I antigen expression. These data indicate that expression of HLA class I antigens is not enhanced on the membrane of hepatocytes with HBV replication, and this may be one factor that permits the development of viral persistence.
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PMID:Hepatic HLA antigen display in chronic hepatitis B virus infection. Relation to hepatic expression of HBV genome/gene products and liver histology. 768 63

Interferons have been evaluated extensively as candidate antiviral agents in hepadnaviral infection. We examined the effect of recombinant human interferon-gamma on duck hepatitis B virus replication in human hepatoma cells (Huh 7) transiently transfected with cloned duck hepatitis B virus DNA. Cells transfected in the presence of interferon-gamma display a dose-dependent reduction in the levels of encapsidated replicative intermediates in the cytoplasm, as judged by Southern blotting of purified viral core DNA. The effect is observed at interferon-gamma concentrations that do not affect growth rate or viability of Huh 7 cells or their transfection efficiency. Northern analysis of duck hepatitis B virus transcripts in transfected cells demonstrated markedly diminished levels of pre- and subgenomic RNA in interferon-gamma-treated cells. Nuclear run-on analysis was performed to determine whether these transcripts were diminished due to decreased rates of transcription initiation or increased rates of RNA degradation. Levels of transcription initiation were unaffected by interferon-gamma, implying that duck hepatitis B virus transcripts in interferon-gamma-treated cells are degraded more rapidly than in untreated cells.
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PMID:Inhibition of duck hepatitis B virus replication by interferon-gamma. 768 9

Hepatocytes in normal tissues express low or undetectable levels of intercellular adhesion molecule-1 (ICAM-1), as detected by immunohistochemistry. Up-regulation of ICAM-1 expression on these cells has been reported in inflammatory liver disease (hepatitis B virus infection, autoimmune liver disorders and liver allograft rejection), and the molecule has been implicated in the recruitment, retention and activation of inflammatory cells. There is, however, little information concerning the regulation of hepatocyte expression of ICAM-1. We show here, for the first time, the induction (within 30 min) of ICAM-1 gene expression in cultured normal human hepatocytes stimulated with interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) or endotoxin. IFN-gamma was the most potent single inducer (up to fourfold at 6 hr), while further induction of ICAM-1 mRNA was achieved with cytokine combinations. Maximal mRNA expression was achieved within 10 hr. ICAM-1 could be detected readily by immunocytochemical staining on the hepatocyte surface by 12 hr, and by enzyme immunoassay in the culture medium by 24 hr. The data present clear evidence that cytokines, which have been implicated previously in inflammatory liver diseases, can up-regulate directly both ICAM-1 gene expression and protein secretion/shedding by human hepatocytes.
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PMID:Proinflammatory cytokines and endotoxin stimulate ICAM-1 gene expression and secretion by normal human hepatocytes. 783 19

Recombinant human granulocyte-macrophage colony-stimulating factor therapy significantly reduces serum hepatitis B virus DNA levels, associated with increased 2',5'-oligoadenylate synthetase activity in cultured mononuclear cells of patients with chronic hepatitis B. To assess changes in immune function during therapy of chronic hepatitis B patients, spontaneous and mitogen-induced production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interferon-alpha and interferon-gamma were measured-along with serum levels of soluble CD4, soluble CD8, soluble interleukin-2 receptor and beta 2-microglobulin-before, during and after a 6-wk course of granulocyte-macrophage colony-stimulating factor in nine patients with chronic hepatitis B. Treatment statistically enhanced spontaneous production of tumor necrosis factor-alpha (p < 0.05) and interleukin-1 beta (p < 0.02). Furthermore, spontaneous interleukin-6 production correlated negatively with hepatitis B virus DNA levels (p < 0.03), and spontaneous interleukin-1 beta production correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.0005). In addition, statistically significant increases were found during therapy in serum levels of soluble interleukin-2 receptor (p < 0.01), soluble CD4 (p < 0.01) and beta 2-microglobulin (p < 0.05). Levels of soluble interleukin-2 receptor and soluble CD4 correlated negatively with levels of hepatitis B virus DNA (p < 0.05), and levels of soluble interleukin-2 receptor and beta 2-microglobulin correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.003 and p < 0.02, respectively). Thus recombinant human granulocyte-macrophage colony-stimulating factor administration may induce reductions in hepatitis B virus DNA levels, perhaps by altering the immune status and increasing cytokine production.
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PMID:Changes in cytokine production during therapy with granulocyte-macrophage colony-stimulating factor in patients with chronic hepatitis B. 792 47


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