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)

There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia.
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PMID:[Interferon-alpha, beta, gamma]. 799 28

Intermittent interferon (IFN) therapy appears to be effective for patients with e-antigen-negative chronic hepatitis B who exhibit abnormal fluctuations of alanine aminotransferase (ALT) levels and histological evidence of disease progression. To determine the optimal dose of IFN in such patients, we studied the effects of natural IFN-beta in a prospective, randomized, double-blind, controlled trial in 36 patients with e-antigen-negative chronic hepatitis B who repeatedly demonstrated abnormal fluctuations in ALT levels. Thirty-six patients were randomly assigned to three groups, receiving doses of: 0.3 MIU IFN (group 1; n = 12), 1 MIU (group 2; n = 12), or 3 MIU (group 3; n = 12), administered twice per week for 24 weeks. Patients were regarded as responders if ALT levels remained within the normal range and HBV-DNA tested negative for 6 months after the initiation of the therapy. According to this criterion, treatment was effective in 16.7% of the patients (2/12) in group 1, 33.3% (4/12) in group 2, and 75% (9/12) in group 3, the efficacy rate in group 3 being significantly higher than that in the other two groups. However, in 12 of the 15 responders, (80%) ALT levels were frequently elevated again within 3 years of the termination of IFN therapy. Although IFN was effective in controlling the manifestations of hepatitis in terms of e-antigen-negative patients who exhibited abnormal fluctuations in ALT, it appears that continuous treatment with intermittent high-dose IFN is necessary to maintain ALT levels within the normal range.
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PMID:A randomized, double-blind, controlled trial of natural interferon-beta therapy for e-antigen-negative chronic hepatitis B patients with abnormal transaminase levels. 884 78

Infection of mice with coronavirus mouse hepatitis virus strain MHV-A59 causes focal acute encephalitis, hepatitis and chronic demyelinating disease. To investigate host interferon (IFN) response to viral infection within the brain, RNA was extracted from A59-or MHV-2- infected and mock-infected primary astrocyte cultures from newborn mice, RT-PCR amplified RNA with primers specific for the various IFNs, transferred to nylon membranes and hybridized with IFN specific digoxigenin-labeled probes. Infection of primary astrocyte cultures from newborn mice with either A59 or MHV-2 caused upregulation of IFN-beta RNA, but not IFN-gamma or IFN-alpha. Thus, brain astrocytes are capable of producing a local IFN-beta response upon infection with MHV. The response of the other IFNs following MHV infection may be derived from inflammatory cells.
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PMID:Coronavirus MHV-A59 causes upregulation of interferon-beta RNA in primary glial cell cultures. 978 14

HCV correlated hepatitis is a pathology on the increase, and it is especially affecting patients above 60 years old. The only treatment for this disease is therapy with different types of interferon. The authors take into examination three of their previous studies on treatment of HCV correlated chronic hepatitis in the elderly using different types of interferon: recombinant interferon alpha, interferon beta, and lymphoblastoid interferon, in order to evaluate which one, among the three, should be the best for the treatment of this pathology in the elderly. The data show that recombinant interferon alpha is preferable since the remission percentage is higher (75%), compared to beta (53.8%) and lymphoblastoid interferon (60%). As far as the relevant side-effects in elderly patients are concerned, beta-interferon therapy is almost with no side-effects. Even in cases where there could be a possible higher exposure to side-effects linked to the use of recombinant interferon alpha, still, the risk/benefit ratio suggests that this particular drug should be used for treating this pathology in elderly patients.
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PMID:Different types of interferon for the therapy of HCV chronic active hepatitis in the elderly patient. 1082 4

To verify the possible effect of IFN-beta treatment on auto antibodies development in multiple sclerosis (MS) we studied 69 MS patients before and during the treatment with IFN-beta 1b (n=35) and IFN-beta 1a (n=20) for 27 and 12 months respectively, and, as controls, 14 untreated MS patients. The serum, collected every 3 months from all the patients, was investigated for the presence of antinuclear (ANA), anti-smooth muscle (ASMA), anti-mitochondrial (AMA), anti-native DNA (nDNA) anti-cardiolipin (aCL), anti-parietal cells (APCA), anti-microsomal (AMC) and anti-tireoglobulin (ATG) antibodies. Among the IFN-beta 1b-treated MS patients an increase of the frequency and of the level of ANA, AMC and ATG was observed. ASMA and ANA antibodies were already present in about 45% of the MS patients before the treatment and fluctuated over the time. In one patient the treatment was interrupted after 6 months because of the occurrence of high ASMA level and of an autoimmune hepatitis. The data obtained in the smaller number of MS patients treated with IFN-beta 1a were very similar. No increase in aCL level was observed during both the IFN treatments. Our results indicate that the treatment with IFN-beta induces an increase of AMC and ATG antibodies in MS patients and confirm that, although rare, autoimmune diseases could be observed. The possible effect of these auto antibodies on the treatment efficacy and on MS clinical course need to be further investigated.
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PMID:Serum auto antibodies presence in multiple sclerosis patients treated with beta-interferon 1a and 1b. 1087 87

Induction of a Th1 immune response against viral infection of the CNS is important in contributing to viral clearance. The present studies demonstrate a role for the T cell chemoattractant chemokine Mig (monokine induced by IFN-gamma) in contributing to a Th1 response against mouse hepatitis virus infection of the CNS. Analysis of the kinetics of Mig expression revealed mRNA transcripts present at days 7 and 12 postinfection (p.i.) but not early (day 2) or late (day 35) in the infection. To determine functional significance, mouse hepatitis virus-infected mice were treated with anti-Mig antisera, and the severity of disease was evaluated. Such treatment resulted in a marked increase in mortality that correlated with a >3 log increase in viral burden within the brains as compared with control mice treated with normal rabbit serum. Anti-Mig-treated mice displayed a significant decrease (p < 0.005) in CD4(+) and CD8(+) T cell recruitment into the CNS as compared with normal rabbit serum-treated mice. In addition, anti-Mig treatment resulted in a significant decrease (p < 0.05) in levels of IFN-gamma and IFN-beta that coincided with increased (p < 0.02) expression of the anti-inflammatory Th2 cytokine IL-10 within the CNS. Collectively, these data indicate that Mig is important in contributing to host defense by promoting a protective Th1 response against viral infection of the CNS.
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PMID:Expression of Mig (monokine induced by interferon-gamma) is important in T lymphocyte recruitment and host defense following viral infection of the central nervous system. 1116 Feb 25

AIM:To assess the possible roles of cytokines (TNF-alpha, IFN-beta, IL-6 and IL-8) in liver damage of hepatitis B.METHODS:The serum TNF-alpha, IFN-beta, IL-6 and IL-8 were detected by ELISA in 66 patients with hepatitis B and 20 healthy blood donors.RESULTS:TNF-alpha and IL-6 in all types of clinical hepatitis B were significantly higher than those in healthy blood donors (P < 0.05); meanwhile the levels of TNF-alpha, IFN-beta, IL-6 and IL-8 in the patients with fulminant hepatitis B were much higher than those in the patients with acute hepatitis B (P < 0.05); the level of TNF-alpha was positively correlated with the levels of IFN-beta, Il-6 and IL-8 in all types of hepatitis B (r(IFN) = 0.24,r(IL6) = 0.35,r(IL8) = 0.44) and the TNF-alpha, IFN-beta, IL-6 and IL-8 were positively correlated with serum bilirubin (P < 0.05). Dynamic changes of these cytokines were observed in the course of acute and fulminant hepatitis. The level of IFN-beta peaked in the initial period of acute hepatitis and early stage of hepatic coma in fulminant hepatitis; TNF-alpha, IL-6 and IL-8 increased with exacerbation, and reached a peak when the liver damage was most serious, then decreased when patient conditions were improved.CONCLUSION:The increased cytokines were related to the inflammation of liver cells and multiple factors may play certain roles in liver damage.
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PMID:Detection of serum TNF-alpha,IFN-beta,IL-6 and IL-8 in patients with hepatitis B. 1181 82

Hepatitis B virus (HBV) is a well known pathogen that sometimes causes fulminant hepatitis in patients undergoing cytotoxic chemotherapy. Fibrosing cholestatic hepatitis (FCH) is a recently recognized unique variant of viral hepatitis, which has been occasionally reported in HBV-infected recipients of liver, renal, or bone marrow transplantation. We present here a 48-yr-old male in whom HBV was reactivated during post-remission chemotherapy for acute myelogenous leukemia, which resulted in rapidly fatal outcome. He manifested with deterioration of liver function in association with enormous replication of HBV. Liver biopsy showed marked ballooning of hepatocytes, cholestasis, and periportal fibrosis with minimum infiltrates. Immunostaining revealed that hepatocytes were strongly positive for hepatitis B surface antigen. Under the diagnosis of FCH, he was treated with lamivudine and interferon beta, which was not effective. Autopsy showed severe atrophy of the liver and marked degeneration of hepatocytes. Hematologists should be aware that FCH is a fatal complication that can develop under post-chemotherapy immunosuppressed conditions. Although there is no convincing evidence, prophylactic administration of lamivudine seems to be a reasonable strategy.
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PMID:Fatal reactivation of hepatitis B virus following cytotoxic chemotherapy for acute myelogenous leukemia: fibrosing cholestatic hepatitis. 1236 13

Limitin has sequence homology with alpha interferon (IFN-alpha) and IFN-beta and utilizes the IFN-alpha/beta receptor. However, it has no influence on the proliferation of normal myeloid and erythroid progenitors. In this study, we show that limitin has antiviral activity in vitro as well as in vivo. Limitin inhibited not only cytopathic effects in encephalomyocarditis virus- or herpes simplex virus (HSV) type 1-infected L929 cells, but also plaque formation in mouse hepatitis virus (MHV) type 2-infected DBT cells. In addition, administration of limitin to mice suppressed MHV-induced hepatitis and HSV-induced death. The antiviral activity may be mediated in part by 2',5'-oligoadenylate synthetase, RNA-dependent protein kinase, and Mx protein, which inhibit viral replication or degrade viral components, because limitin induced their mRNA expression and enzyme activity. While limitin has antiviral activity as strong as that of IFN-alpha in vitro (the concentration that provided 50% inhibition of cytopathic effect is approximately 30 pg/ml), IFN regulatory factor 1 (IRF-1) dependencies for induction of an antiviral state were different for limitin and IFN-alpha. In IRF-1-deficient fibroblasts, a higher concentration of limitin than of IFN-alpha was required for the induction of antiviral activity and the transcription of proteins from IFN-stimulated response element. The unique signals and the fewer properties of myelosuppression suggest that a human homolog of limitin may be used as a new antiviral drug.
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PMID:Antiviral activity of limitin against encephalomyocarditis virus, herpes simplex virus, and mouse hepatitis virus: diverse requirements by limitin and alpha interferon for interferon regulatory factor 1. 1291 74

Innate cellular antiviral defenses are likely to influence the outcome of infections by many human viruses, including hepatitis B and C viruses, agents that frequently establish persistent infection leading to chronic hepatitis, cirrhosis, and liver cancer. However, little is known of the pathways by which hepatocytes, the cell type within which these hepatitis agents replicate, sense infection, and initiate protective responses. We show that cultured hepatoma cells, including Huh7 cells, do not activate the interferon (IFN)-beta promoter in response to extracellular poly(I-C). In contrast, the addition of poly(I-C) to culture media activates the IFN-beta promoter and results in robust expression of IFN-stimulated genes (ISG) in PH5CH8 cells, which are derived from non-neoplastic hepatocytes transformed with large T antigen. Small interfering RNA knockdown of TLR3 or its adaptor, Toll-interleukin-1 receptor domain-containing adaptor inducing IFN-beta (TRIF), blocked extracellular poly(I-C) signaling in PH5CH8 cells, whereas poly(I-C) responsiveness could be conferred on Huh7 hepatoma cells by ectopic expression of Toll-like receptor 3 (TLR3). In contrast to poly(I-C), both cell types signal the presence of Sendai virus infection through a TLR3-independent intracellular pathway requiring expression of retinoic acid-inducible gene I (RIG-I), a putative cellular RNA helicase. Silencing of RIG-I expression impaired only the response to Sendai virus and not extracellular poly(I-C). We conclude that hepatocytes contain two distinct antiviral signaling pathways leading to expression of type I IFNs, one dependent upon TLR3 and the other dependent on RIG-I, with little cross-talk between these pathways.
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PMID:Distinct poly(I-C) and virus-activated signaling pathways leading to interferon-beta production in hepatocytes. 1573 93


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