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)

The pathogenesis of hepatitis C virus-induced chronic liver disease is still poorly understood. Previous studies revealed enhanced hepatic expression of the Th1 prototype cytokine IFN-gamma in individuals with chronic hepatitis C. In accordance with several animal models of experimentally induced hepatitis, a Th1 lymphocyte driven inflammatory process, which involves newly infiltrated as well as resident monocytes/macrophages, has been proposed. An involvement of the interferon-gamma-inducible chemokine IP-10, which is chemoattractive for stimulated Th1 cells and monocytes, is also suggested. Using an HBV transgenic mouse model, a reduction of hepatic infiltration and liver disease was achieved recently by administration of antibodies directed against the interferon-gamma-inducible chemokine Mig and against IP-10. In the present study, expression of IP-10 was investigated both in serum and in the liver of patients with chronic hepatitis C and hepatitis B. Patients with liver diseases of non-viral etiologies served as controls. IP-10 expression was highest in hepatitis C. In chronic hepatitis C, but not in chronic hepatitis B nor in liver disorders unrelated to viral infections, IP-10 expression was strongly correlated with the amount of transcripts for IFN-gamma and to the amount of transcripts for the constitutively expressed macrophage derived cytokine IL-18. Hepatic inflammatory activity, however, was found to be associated more closely with IFN-gamma than with IP-10 or IL-18 mRNA expression. The data support the hypothesis that IP-10 is responsible for the recruitment of Th cells and monocytes in chronic hepatitis C, and suggest that its role in chronic hepatitis B is less determining. Moreover, they deliver additional support for the view that IFN-gamma still has to be considered as a mediator that determines the outcome of inflammation, e.g., via its ability to activate IL-18 expressing cells and to initiate a delayed type hypersensitivity reaction.
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PMID:Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFN-gamma and IL-18 mRNA in chronic hepatitis C but not in hepatitis B. 1279 18

It is known that some viruses are able to induce vigorous immune reactions. This study shows that inactivated parapoxvirus ovis (Orf virus), strain D1701 (PPVO), induces an autoregulatory cytokine response that involves the upregulation of IL-12, IL-18, IFN-gamma and other T helper 1-type cytokines and their subsequent downregulation, which is accompanied by induction of IL-4. An increase in IL-10 expression was also found in the livers of PPVO-treated mice. PPVO protects mice from lethal herpes simplex virus type 1 infection and guinea pigs from recurrent genital herpes disease. With dosages as low as 500 000 virus particles, PPVO is more potent than the current standard 3TC therapy in hepatitis B virus transgenic mice. No signs of inflammation or any other side effects were observed. PPVO induces IL-12, TNF-alpha and, together with a suboptimal concentration of Concanavalin A, IFN-gamma in human peripheral blood leukocytes as well. The principle of an autoregulatory cytokine induction by an inactivated virus might have advantages over existing immune therapies and it is concluded that inactivated PPVO should be investigated further for its potential use in antiviral therapy.
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PMID:Inactivated parapoxvirus ovis (Orf virus) has antiviral activity against hepatitis B virus and herpes simplex virus. 1281 Aug 78

By using the hepatitis B core (HBc) protein gene as a carrier, HIV-1 env V3 gene was inserted into the carrier gene, and the HIV gene was expressed inside a chimeric HIV-HBc particle (HIV-HBc), which was a unique candidate for induction of HIV-specific CTL activity. This was seen significantly in mice without the need of an adjuvant, because other responses specific for the HIV peptide such as T-cell proliferation and antibody production were not induced. However, when hemagglutinating virus of Japan (HVJ) protein was incorporated into an anionic liposome containing HIV peptide (HIV-HVJ-liposome) and was used as a booster immunization in HIV-HBc primed animals, the HIV-specific T-cell response and enhanced CTL activity were clearly induced in consecutively immunized animals. Furthermore, the HIV-specific humoral immune response was also induced and a neutralization activity was detected in the immune sera. Thus, when an HIV peptide antigen is expressed inside the virus like a particle of HBc, it can induce both cellular and humoral immunities when an HVJ-HIV-liposome, but not an HIV-liposome, is inoculated as the booster antigen. The HVJ-stimulated splenocytes secreted IL-18 and IL-12 to synergistically enhance the secretion of IFN-gamma in vitro. These findings suggest that the HVJ protein is effective at inducing the HIV-specific immunities, if used as part of a booster antigen in the consecutive immunization regimen.
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PMID:Hemagglutinating virus of Japan protein is efficient for induction of CD4+ T-cell response by a hepatitis B core particle-based HIV vaccine. 1520 86

Hepatitis B virus (HBV) superinfection in chronic hepatitis C represents a natural model to investigate whether or not hepatitis C virus (HCV) can influence priming and maturation of antiviral T cells; whether or not HBV superinfection, which is known to determine control of HCV replication, can restore HCV-specific T cell responsiveness; and whether or not cytokines stimulated by HBV infection can contribute to HCV control. To address these issues, the function of CD8 cells specific for HBV and HCV was studied longitudinally in two chronic HCV patients superinfected with HBV. Patients with acute hepatitis B were also examined. Frequency and function of HBV tetramer+ CD8 cells were comparable in patients acutely infected with HBV with or without chronic HCV infection. HBV-specific CD8 cell function was efficiently expressed irrespective of serum HCV-RNA levels. Moreover, fluctuations of HCV viremia at the time of HBV superinfection were not associated with evident changes of CD8 responsiveness to HCV. Finally, no correlation was found between serum levels of interferon alpha, interleukin (IL)-12, IL-10, or IL-18 and control of HCV replication. In conclusion, HCV did not affect the induction of primary and memory HBV-specific CD8 responses. HCV-specific CD8 responses were undetectable when HCV-RNA was negative, showing that inhibition of HCV replication in the setting of a HBV superinfection was not sufficient to induce a restoration of CD8 reactivity against HCV.
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PMID:Antiviral CD8-mediated responses in chronic HCV carriers with HBV superinfection. 1536 33

The influence of IL-12 and IL-18 was evaluated on hepatitis B core antigen (HBcAg)-specific cytokine production (IFN-gamma, IL-4, IL-5 and IL-10) by CD4 T lymphocytes isolated from peripheral blood of children with chronic hepatitis B. CD4 T cells were isolated from peripheral blood of 20 children with chronic active hepatitis B, cultured for 48h in presence of rHBcAg and of co-stimulators, IL-12 or IL-18 or IL-12+IL-18 or in their absence (control). Production of studied cytokines was examined using the ELISPOT assay. Co-stimulation with IL-12 or IL-18 was found to significantly augment the HBcAg-specific secretion of IFN-gamma. However, the most pronounced stimulatory effect was observed in the presence of IL-12+IL-18 and resulted in peak levels of IFN-gamma production. The obtained results allowed concluding that the anti-HBV activity of Th1 lymphocytes is strongly induced by IL-12+IL-18 and may contribute to viral clearance in children with chronic hepatitis B infection.
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PMID:Effects of IL-12 and IL-18 on HBcAg-specific cytokine production by CD4 T lymphocytes of children with chronic hepatitis B infection. 1578 Nov 28

The liver protects the host from gut-derived pathogens yet is tolerant of antigenic challenge from food and commensal sources. Innate responses involving liver macrophages (Kupffer cells) and effector liver natural killer (NK) cells form the first line in this defense. We address the impact of Toll-like receptor (TLR) signaling on the cross talk between these two cells, and reveal how the liver displays a down-regulated inflammatory response to constitutive bacterial elements through the secretion of interleukin (IL) 10 yet retains a vigorous response to viral challenge. The data support the model that (a) human liver Kupffer cells respond to TLR ligands and indirectly activate NK cells; (b) the activation depends on cell-cell contact; (c) the Kupffer cells synthesize NK cell activating signals, among which IL-18 is critical, and NK cell inhibitory factors, including IL-10; (d) ligands that signal via myeloid differentiation factor 88 induce IL-10, giving a blunted response in the NK cells; and (e) ligands that signal via the Toll-IL-1 receptor domain-containing adaptor inducing interferon (IFN) beta-IFN regulatory factor 3 pathway induce less IL-10, and also directly potentiate the stimulatory effect of IL-18 on NK cells, resulting in enhanced activation. Subversion of cellular mechanisms of innate immune response against viruses may be important for hepatotropic viruses (e.g., hepatitis B and C) to develop persistence.
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PMID:TLR-dependent cross talk between human Kupffer cells and NK cells. 1819 76

Hepatitis B is a global serious disease caused by hepatitis B virus (HBV). There is no known cure for hepatitis B. The best way to deal with the disease is by preventing with hepatitis B vaccine. However, the current protein-based vaccines made up of recombinant hepatitis B surface antigen (HBsAg) are ineffective in chronic HBV carriers and a significant number of the vaccinees do not mount the protective immune response. Novel DNA-based immunization may overcome the deficits of the protein-based immunization and may provide more effective prophylactic and therapeutic outcomes. In this study, we constructed a recombinant plasmid carrying gene encoding the HBV surface antigen (HBs) linked to DNA segment encoding full-length murine interleukin-18, i.e. pcDNA-HBs-IL-18. Immunogenicity of the DNA construct was carried out in BALB/c mice in comparison with mock, i.e. pcDNA3.1+ and vaccines comprised of pRc/CMV-HBs and pRc/CMV-HBs plus pcDNA-IL-18. All vaccinated mice revealed significant serum anti-HBs IgG response after two intramuscular injections of the vaccines at 28 day interval as compared to the level of mock. Co-administration of pRc/CMV-HBs and pcDNA-IL-18 elicited arbitrarily higher levels of anti-HBs IgG than the levels in mice immunized with pRc/CMV-HBs alone and mice that received pcDNA-HBs-IL-18 although not statistically different. Further experiments are needed to investigate the subisotypes of the IgG antibody, the kinetics of cytokine and the cell-mediated immune response. For this communication, the prototype HBs-IL-18 DNA vaccine was successfully constructed and the gene encoding murine IL-18 was successfully cloned. The latter can be co-injected with the antigen coding DNA or used as a fusion partner to the DNA for priming the immune response. The recombinant HBs and full-length IL-18 proteins have potential for other research purposes. They may be used also as standard proteins in the protein quantification assay.
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PMID:Cloning, protein expression and immunogenicity of HBs-murine IL-18 fusion DNA vaccine. 1840 97

Characterization of the immune responses induced in the initial stages of human immunodeficiency virus type 1 (HIV-1) infection is of critical importance for an understanding of early viral pathogenesis and prophylactic vaccine design. Here, we used sequential plasma samples collected during the eclipse and exponential viral expansion phases from subjects acquiring HIV-1 (or, for comparison, hepatitis B virus [HBV]or hepatitis C virus [HCV]) to determine the nature and kinetics of the earliest systemic elevations in cytokine and chemokine levels in each infection. Plasma viremia was quantitated over time, and levels of 30 cytokines and chemokines were measured using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. The increase in plasma viremia in acute HIV-1 infection was found to be associated with elevations in plasma levels of multiple cytokines and chemokines, including rapid and transient elevations in alpha interferon (IFN-alpha) and interleukin-15 (IL-15) levels; a large increase in inducible protein 10 (IP-10) levels; rapid and more-sustained increases in tumor necrosis factor alpha and monocyte chemotactic protein 1 levels; more slowly initiated elevations in levels of additional proinflammatory factors including IL-6, IL-8, IL-18, and IFN-gamma; and a late-peaking increase in levels of the immunoregulatory cytokine IL-10. Notably, there was comparatively little perturbation in plasma cytokine levels during the same phase of HBV infection and a delayed response of more intermediate magnitude in acute HCV infection, indicating that the rapid activation of a striking systemic cytokine cascade is not a prerequisite for viral clearance (which occurs in a majority of HBV-infected individuals). The intense early cytokine storm in acute HIV-1 infection may have immunopathological consequences, promoting immune activation, viral replication, and CD4(+) T-cell loss.
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PMID:Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. 1917 32

The outcome of hepatitis B virus (HBV) infection can be affected by host immune factors. Interleukin-18 (IL-18) was originally discovered as an interferon-gamma-inducing factor and plays a critical role in immune response. We assessed the association between the clearance of HBV infection and single-nucleotide polymorphisms (SNPs) in the IL-18 gene. Between March 2002 and December 2004, a total of 1,050 Korean subjects were enrolled in the study and divided into two groups: (1) the HBV spontaneous recovery group (n = 320) and (2) the chronic HBV carrier group (n = 730). We analyzed SNPs at four polymorphic sites in the IL-18 gene at positions -667G>T, -148G>C, +8925C>G, and +13925A>C. We observed that the subjects bearing the IL-18 -148C allele [odds ratio (OR), 0.25; confidence interval (CI), 0.09-0.68; P = 0.01], the +8925G allele (OR, 0.36; CI, 0.15-0.88; P = 0.02), and the +13925C allele (OR, 0.25; CI, 0.13-0.82; P = 0.01) were significantly associated with HBV clearance in a recessive model. This study indicates that the -148C, +8925G, and +13925C alleles of the IL-18 gene are likely associated with HBV clearance in a Korean population.
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PMID:Association of interleukin-18 gene polymorphisms with hepatitis B virus clearance. 1946 45

Hepatocellular carcinoma (HCC) is a frequent malignancy with a high rate of mortality, and the hepatitis B and C viruses are considered major etiological factors associated with the development of chronic inflammation. Today, there is increasing evidence that the inflammatory process, mediated by the complex cytokine network, is inherently associated with many cancer types, including HCC. In this study we have assayed Th1 cytokines, such as IL-18 and IFN gamma, in the sera of 23 HCC patients with HCV infection, analysing their possible association with HCC in respect to 20 patients: 12 carriers for HCV infection and 8 healthy controls. We have also evaluated the possible difference on IL-18 and IFN gamma in HCC patients with respect to the number of hepatic nodules and rate of tumor differentiation. The mean values of serum IL-18 levels were significantly higher in HCC patients than in HCV carriers (p < 0.001) while IFN gamma serum levels were similar in cases and controls. No significant correlation was present between IL-18 and IFN gamma. In addition, IL-18 was higher in HCC patients with two or more nodules in respect to HCC patients with one nodule (372+/-140 vs 109+/-73 pg /mL; p <0.001). There is no significant difference in HCC patients and no correlation between the cytokines and other evaluated variables such as HCV RNA, alpha-1 fetoprotein, genotype and demographics of HCC patients. Taken together, our data suggest that IL-18 may play a key role in the pathogenesis of HCC and its levels can be utilized as a possible marker in the diagnosis of HCC.
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PMID:IL-18 and interferon-gamma in HCV-related hepatocellular carcinoma: a model of interplay between immune status and cancer. 2000 64


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