{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T05:16:32Z","timestamp":1770700592186,"version":"3.49.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":8400,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,9]]},"abstract":"\n \n The role that inflammatory cytokines may play in the life cycle of the hepatitis B virus and in the pathogenesis of its associated liver disease has not been carefully delineated. In this report, we demonstrate that bacterial lipopolysaccharide, a potent inducer of inflammatory cytokines in vivo<\/jats:italic>, causes a severe acute liver disease in transgenic mice whose hepatocytes produce the hepatitis B virus large envelope polypeptide and retain HBsAg within the endoplasmic reticulum. In contrast, 100\u2013fold higher doses of bacterial lipopolysaccharide do not induce liver cell injury in nontransgenic littermate controls or in transgenic mice whose hepatocytes secrete HBsAg rather than retain it. Coincident with the hepatocellular injury and the influx of inflammatory cells into the liver, a marked reduction occurs in the intrahepatic content of hepatitis B virus steady\u2013state messenger RNA, thereby confirming the selectivity of this process for the HBsAg\u2013positive hepatocyte. Bacterial lipopolysaccharide\u2013induced hepatocellular injury appears to be principally mediated by interferon\u2013\u03b3 because it can be markedly reduced by the prior administration of neutralizing interferon\u2013\u03b3-specific monoclonal antibodies and because recombinant interferon\u2013\u03b3 is also selectively cytotoxic for the HBsAg\u2013positive transgenic hepatocyte in vivo.<\/jats:italic> Tumor necrosis factor-\u03b1 is also involved in this process because bacterial lipopolysaccharide\u2013induced liver cell injury is significantly reduced by tumor necrosis factor-\u03b1 specific monoclonal antibodies. The role of tumor necrosis factor-\u03b1 in bacterial lipopolysaccharide-induced liver cell injury is less clear than interferon\u2013\u03b3, however, because unlike interferon\u2013\u03b3 it is also toxic for nontransgenic hepatocytes. These results demonstrate that the HBsAg\u2013positive transgenic mouse hepatocyte is selectively sensitive to destruction by interferon\u2013\u03b3 in vivo.<\/jats:italic> Because this cytokine has been shown to be produced by intrahepatic lymphocytes during viral hepatitis in humans, these results raise the possibility that a similar pathway may contribute to the clearance of HBsAg\u2013positive hepatocytes and to the pathogenesis of liver cell injury in human HBV infection as well. (Hepatology 1992;16:655-663.)<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.1840160308","type":"journal-article","created":{"date-parts":[[2007,3,4]],"date-time":"2007-03-04T01:06:16Z","timestamp":1172970376000},"page":"655-663","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":103,"title":["Hbsag Retention Sensitizes the Hepatocyte to Injury by Physiological Concentrations of Interferon\u2013\u03b3"],"prefix":"10.1097","volume":"16","author":[{"given":"Patrick N.","family":"Gilles","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah L.","family":"Guerrette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Ulevitch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert D.","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis V.","family":"Chisari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840160308-BIB1","first-page":"741","volume-title":"The liver and the biliary system in pathology","author":"Rubin","year":"1988","unstructured":". 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