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)

Intercellular adhesion molecule 1 (ICAM-1), a counter-receptor for lymphocyte function-associated antigen 1 on T cells, is critically important to a wide variety of adhesion-dependent leukocyte functions, including antigen presentation and target cell lysis. ICAM-1 expression by hepatocytes is increased in areas of inflammation and necrosis during chronic hepatitis B. Whether induction of ICAM-1 is due to the effect of inflammatory cytokines or involves a direct effect of the hepatitis B virus (HBV) remains unknown. In the present study, transfection of the HBV genome into human hepatoma cell lines resulted in enhanced expression of ICAM-1 protein and RNA in the absence of inflammation. Results of subgenomic transfections indicated that the HBV X protein (pX) induced ICAM-1 expression. Nuclear run-on assays showed that pX induced the ICAM-1 gene by increasing its rate of transcription. Although both pX and interferon gamma induced transcription of ICAM-1, addition of interferon gamma to cells expressing pX did not show an additive or synergistic effect. These results indicate that pX can directly regulate expression of ICAM-1 and may participate in the immunopathogenesis of HBV infection.
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PMID:Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B virus X protein. 136 Jun 68

To examine the relationship between hepatitis B core antigen-specific interferon gamma production and the liver injury, we measured the sequential change in this production by peripheral blood mononuclear cells of seven patients with chronic hepatitis B. Four patients who experienced acute exacerbation showed increased interferon gamma production when the serum alanine aminotransferase level peaked or during the recovery phase. In the three patients who did not experience acute exacerbation, interferon gamma production gradually decreased in one who had a low peak of alanine aminotransferase but did not show significant change in the other two. Increased production of hepatitis B core antigen-specific interferon gamma at the time of acute exacerbation suggests that interferon gamma induced by hepatitis B core antigen plays a role in hepatocellular injury of patients with chronic hepatitis B.
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PMID:Hepatitis B core antigen-specific interferon gamma production of peripheral blood mononuclear cells during acute exacerbation of chronic hepatitis B. 138 10

Thirty-five children with chronic hepatitis B were randomly assigned to three groups: group 1 (n = 12), untreated; group 2 (n = 11), treated with 1 million units of interferon gamma per square meter of body surface (MU/m2), three times a week for 24 weeks; and group 3 (n = 12), treated with interferon alfa at a dose of 5 MU/m2, three times a week for 12 weeks followed by 1 MU/m2 of interferon gamma with the same schedule. At the end of the treatment (6th month), hepatitis B virus DNA was negative in 16.5% of the control group, in 9% of the children treated with interferon gamma, and in 16.5% of those treated with interferons alfa and gamma. No child had lost the hepatitis B e antigen by this time. No basal differences in the serum hepatitis B virus DNA concentration among the groups were observed. At follow-up (15th month), viral genome was negative in 25% of the untreated children, in 36% of the group treated with interferon gamma, and in 41.5% of the children who had received interferons alfa and gamma. Hepatitis B e antigen was negative in 25% of the children who belonged to groups 1 and 3 and in 27% of the children treated with interferon gamma only. These data suggest that interferon gamma does not have a powerful antiviral effect on chronic hepatitis B in children. However, it is well tolerated.
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PMID:Treatment with interferon gamma versus interferons alfa and gamma in children with chronic hepatitis B. 164 Dec 92

To examine whether Sho-saiko-to (kampo medicine) could modulate the immune response of immunocompetent cells to hepatitis B virus (HBV)-associated antigens, we investigated in vitro interferon gamma (IFN-gamma) and antibody (antibody to HB core and e antigens; anti-HBc and anti-HBe) production by peripheral blood mononuclear cells (PBMC) from eight patients with chronic active hepatitis (CAH) (four with HBeAg and four with anti-HBe) in the presence of recombinant HBcAg and purified HBeAg. IFN-gamma and antibody production were measured using ELISA and RIA, respectively. PBMC from both HBeAg and anti-HBe positive patients generated significantly increased IFN-gamma and antibody (anti-HBc and anti-HBe) production in the culture containing Sho-saiko-to (TJ-9) in a dose-dependent manner in comparison with those of medium alone culture. Similarly, when various concentrations of TJ-9 were added to the HBV antigen-stimulated cultures, TJ-9 was found to enhance both IFN-gamma and antibody production dose-dependently. These results indicate that TJ-9 is able to modulate both cellular and humoral immune responses specific for HBV-associated antigens. These findings also may account for, at least in part, the efficacy of TJ-9 treatment for type B chronic hepatitis.
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PMID:Effects of TJ-9 Sho-saiko-to (kampo medicine) on interferon gamma and antibody production specific for hepatitis B virus antigen in patients with type B chronic hepatitis. 190 36

Interferons are proteins elaborated by infected cells that protect noninfected cells from viral infection. These proteins produce a temporary "antiviral state" by altering nucleotide metabolism and cytoplasmic enzyme induction. Interferons appear early after viral infection locally and systematically to limit spread of viral infection; they also affect cell differentiation, growth, surface, antigen expression, morphologic findings, and immunoregulation. Several human disorders have diminished interferon production. Newborns have normal interferon alpha but deficient interferon gamma production. Infants with congenital infections may also have defects in interferon production. Immunosuppressed patients receiving transplants (marrow, heart, of kidney) have diminished interferon production, particularly immediately after transplant. Deficiencies of interferon have also been noted in Down's syndrome, cellular immunodeficiencies, uremia, malnutrition, and hematopoietic malignancy. Leukocyte interferon has been of therapeutic value in herpes zoster infections, in patients with cancer, and in patients with hepatitis B infection. Interferon has not been proved to help children with congenital cytomegalovirus or rubella. Interferon can shrink lymphoid tumors, particularly non-Hodgkin's lymphoma.
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PMID:UCLA conference. Interferon: immunobiology and clinical significance. 617 66

A recent study indicated that thymic hormones have antiviral effects in human hepatitis B virus infection and woodchuck hepatitis virus infection. These hormones are known to exert immunomodulatory effects on lymphocyte maturation and function; because these are abnormal in patients with chronic hepatitis B virus infection, we have examined the effects of a thymic hormone (THF gamma 2) on peripheral blood mononuclear cells from patients with chronic hepatitis B virus infection. THF gamma 2 (50 or 150 ng/ml) alone was without effect; in the presence of low doses of the mitogen phytohaemagglutinin, it had a broad effect in patients and controls. The effect on interleukin-2 production was greater in patients than controls with a significant increase in production at 150 ng/ml for patients alone (p = 0.037). Tumour necrosis factor alpha production was enhanced in all patients and controls, with a greater effect seen at 150 ng/ml THF gamma 2 than 50 ng/ml. There was no effect on interferon gamma production or on the expression of membrane markers of T-cell activation. THF gamma 2 has substantial immunomodulatory activity in chronic hepatitis B virus carriers and in vivo assessment of THF gamma 2 in chronic hepatitis B virus is indicated.
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PMID:THF gamma 2 stimulates cytokine release by peripheral blood mononuclear cells of patients with chronic hepatitis B virus infection. 751 50

Approximately 5% of the world population is infected by the hepatitis B virus (HBV) that causes a necroinflammatory liver disease of variable duration and severity. Chronically infected patients with active liver disease carry a high risk of developing cirrhosis and hepatocellular carcinoma. The immune response to HBV-encoded antigens is responsible both for viral clearance and for disease pathogenesis during this infection. While the humoral antibody response to viral envelope antigens contributes to the clearance of circulating virus particles, the cellular immune response to the envelope, nucleocapsid, and polymerase antigens eliminates infected cells. The class I- and class II-restricted T cell responses to the virus are vigorous, polyclonal, and multispecific in acutely infected patients who successfully clear the virus, and the responses are relatively weak and more narrowly focused in chronically infected patients who do not. The pathogenetic and antiviral potential of the cytotoxic T lymphocyte (CTL) response to HBV has been demonstrated by the induction of a severe necroinflammatory liver disease following the adoptive transfer of HBsAg-specific CTL into HBV transgenic mice, and by the noncytolytic suppression of viral gene expression and replication in the same animals by a posttranscriptional mechanism mediated by interferon gamma, tumor necrosis factor alpha, and interleukin 2. The dominant cause of viral persistence during HBV infection is the development of a weak antiviral immune response to the viral antigens. While neonatal tolerance probably plays an important role in viral persistence in patients infected at birth, the basis for poor responsiveness in adult-onset infection is not well understood and requires further analysis. Viral evasion by epitope inactivation and T cell receptor antagonism may contribute to the worsening of viral persistence in the setting of an ineffective immune response, as can the incomplete downregulation of viral gene expression and the infection of immunologically privileged tissues. Chronic liver cell injury and the attendant inflammatory and regenerative responses create the mutagenic and mitogenic stimuli for the development of DNA damage that can cause hepatocellular carcinoma. Elucidation of the immunological and virological basis for HBV persistence may yield immunotherapeutic and antiviral strategies to terminate chronic HBV infection and reduce the risk of its life-threatening sequellae.
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PMID:Hepatitis B virus immunopathogenesis. 761 25

During hepatitis B virus (HBV) infection, distinct host-virus interactions may establish the patterns of viral clearance and persistence and the extent of virus-associated pathology. It is generally thought that HBV-specific class I-restricted cytotoxic T lymphocytes (CTLs) play a critical role in this process by destroying infected hepatocytes. This cytopathic mechanism, however, could be lethal if most of the hepatocytes are infected. In the current study, we demonstrate that class I-restricted HBV-specific CTLs profoundly suppress hepatocellular HBV gene expression in HBV transgenic mice by a noncytolytic process, the strength of which greatly exceeds the cytopathic effect of the CTLs in magnitude and duration. We also show that the regulatory effect of the CTLs is initially mediated by interferon gamma and tumor necrosis factor alpha, is delayed in onset, and becomes independent of these cytokines shortly after it begins. The data indicate that the anti-viral CTL response activates a complex regulatory cascade that inhibits hepatocellular HBV gene expression without killing the cell. The extent to which this mechanism contributes to viral clearance or viral persistence during HBV infection remains to be determined.
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PMID:Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. 817 Sep 85

The molecular and cellular mechanisms responsible for cytotoxic T lymphocyte (CTL)-induced immunopathology are not well defined. Using a model in which hepatitis B surface antigen (HBsAg)-specific CTL cause an acute necroinflammatory liver disease in HBsAg transgenic mice, we demonstrate that class I-restricted disease pathogenesis is an orderly, multistep process that involves direct as well as indirect consequences of CTL activation. It begins (step 1) almost immediately as a direct antigen-specific CTL-target cell interaction that triggers the HBsAg-positive hepatocyte to undergo programmed cell death (apoptosis). It progresses (step 2) within hours to a focal inflammatory response in which antigen-nonspecific lymphocytes and neutrophils amplify the local cytopathic effect of the CTL. The most destructive pathogenetic function of the CTL, however, is to secrete interferon gamma when they encounter antigen in vivo, thereby activating the intrahepatic macrophage and inducing a delayed-type hypersensitivity response (step 3) that destroys the liver and kills the mouse. We propose that the principles illustrated in this study are generally applicable to other models of class I-restricted, CTL-induced immunopathology, and we suggest that they contribute to the immunopathogenesis of viral hepatitis during hepatitis B virus infection in humans.
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PMID:Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis. 822 7

Hepatitis B virus (HBV) DNA contains consensus elements for transactivating proteins whose binding activity in other systems is regulated by inflammatory cytokines. Because HBV replicates within an environment of provoked inflammation, we speculated that the HBV core/pregenomic promoter may be regulated by cytokines produced in response to infection. To evaluate this hypothesis, the HBV core/pregenomic (C/P) promoter and associated cis-acting elements were placed upstream of a luciferase-encoding plasmid. This reporter construct was transfected into cytokine-sensitive hepatoma cells permissive for HBV replication, which were exposed to stimulated mononuclear cell-conditioned medium or human recombinant cytokines. Conditioned medium reduced luciferase expression by 80%. Tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) each reduced luciferase activity by 40%. Combinations of TNF-alpha and interferons mimicked the extent of conditioned medium inhibition. Non-specific effects from diminished cellular viability or growth were not responsible for decreased luciferase activity. Retention of HBV DNA 330 basepairs upstream of the C/P transcription start site was required to maintain the TNF-alpha effect. A 60% reduction in HBV replicative forms within intracellular core particles was demonstrated with TNF-alpha treatment of Hep G2 cells stably transfected with HBV DNA. The inhibitory action of these cytokines implicates a noncytolytic mechanism by which antigen-nonspecific immune responses in part regulate HBV replication in infected hepatocytes. This function may be beneficial in accelerating viral clearance, but in alternative circumstances could contribute to viral persistence by attenuating immunogen recognition.
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PMID:Cytokine inhibition of the hepatitis B virus core promoter. 855 37


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