HepatologyVolume 20, Issue 3 p. 762-764 Hepatology ElsewhereFree Access The role of inflammatory mediators on hepatitis B virus surface expression in a transgenic mouse model First published: September 1994 https://doi.org/10.1002/hep.1840200331AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract We have recently reported that administration of recombinant tumor necrosis factor-alpha to hepatitis B virus transgenic mice reduces the hepatic steadystate content of HBV-specific mRNA by up to 80% in the absence of liver cell injury. In the current study, we analyzed the regulatory effects of several other inflammatory cytokines in the same transgenic model system. Hepatic HBV mRNA content was reduced by up to 90% following administration of a single noncytopathic dose (100,000U) of interleukin-2. Comparable effects were produced by administration of alpha and beta interferons, but only after multiple injections of at least 500,000U per mouse. Importantly, the regulatory effect of IL-2 was completely blocked by the prior administration of antibodies to tumor necrosis factor-α, which did not block the effect of IFN-α or IFN-β. In contrast to these observations, recombinant IFNg, IL-1, IL-3, IL-6, TNF-β, transforming growth factor-β and granulocyte-monocyte colony stimulating factor were inactive in this system. These results suggest that selected inflammatory cytokines can down-regulate HBV gene expression in vivo by at least two pathways, one that is dependent on TNF-α and another that is not. These results imply that antigen-nonspecific products of the intrahepatic HBV-specific inflammatory response may contribute to viral clearance or persistence during HBV infection. References 1 Missale G, Redeker A, Person J, Fowler P, Guilhot S, Schlicht HJ, Ferrari C, et al. HLA-A31 and HLA-Aw68 restricted cytotoxic T-cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis. J Exp Med 1993; 177: 751– 762. 2 Nayersina R, Fowler P, Guilhot S, Missale G, Cernay A, Schlicht HJ, Vitiello A, et al. HLA A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection. J Immunol 1993; 150: 4659– 4671. 3 Ando K, Moriyama T, Wirth S, Schreiber RD, Schlicht HJ, Huang S, Chisari FV. Mechanisms of class I restricted immunopathology: a transgenic mouse model of fulminant hepatitis. J Exp Med 1993; 178: 1541– 1554. 4 Wong GHW, Goeddel DV. Tumour necrosis factors-α and -β inhibit virus replication and synergize with interferons. Nature 1986; 323: 819– 822. 5 Poli G, Kinter AL, Justement JS, Bressier P, Kehrl JH, Fauci AS. Transforming growth factor-β suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage. J Exp Med 1991; 173: 589– 597. 6 Gilles PN, Fey G, Chisari FV. Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice. J Virol 1992; 66: 3955– 3960. 7 Lau JYN, Bain VG, Naoumov NV, Smith HM, Alexander GJM, Williams R. Effect of interferon-γ on hepatitis B viral antigen expression in primary hepatocyte culture. Hepatology 1991; 14: 975– 979. 8 Lavine JE, Ganem D. Inhibition of duck hepatitis B virus replication by interferon-gamma. J Med Virol 1993; 40: 59– 64. 9 Hayashi Y, Koike K. Interferon inhibits hepatitis B virus replication in a stable expression system of transfected viral DNA. J Virol 1989; 63: 2936– 2940. 10 Caselmann WH, Meyer M, Scholz S, Hofschneider PH, Koshy R. Type I interferons inhibit hepatitis B virus replication and induce hepatocellular gene expression in cultured liver cells. J Infect Dis 1992; 166: 966– 971. 11 Tur-Kaspa R, Teicher L, Laub O, Itin A, Dagan D, Bloom BR, Shrafritz DA. Alpha interferon suppresses hepatitis B virus enhancer activity and reduces viral gene transcription. J Virol 1990; 64: 1821– 1824. Volume20, Issue3September 1994Pages 762-764 ReferencesRelatedInformation