Influence of Ethanol Consumption on Experimental Viral Hepatitis

Abstract

Background One important contributor to pathologic effects on the liver associated with alcohol abuse is viral hepatitis, especially hepatitis C virus (HCV) infection. Alcohol consumption has been shown to be associated with more severe HCV infection and hepatitis. The mechanisms of the more severe viral infection of the liver are unclear, and studies have been hampered by the lack of an animal model of hepatotropic viral infections. Methods We have established a murine model system of viral hepatitis in which C57BL/6 mice are infected with murine cytomegalovirus, a herpesvirus that produces self-limiting hepatitis in immunocompetent mice. Mice were fed a liquid diet containing 36% ethanol-derived calories with a pair-feeding protocol. After infection with a sublethal dose of murine cytomegalovirus, the severity of liver infection was determined by measuring serum levels of alanine aminotransferase and by histological evaluation. Other parameters determined included the serum levels of cytokines, cytokine RNA in liver samples, and viral concentration in liver samples. Results Ethanol-fed mice showed more severe hepatitis in the later stages of the infection as compared with the hepatitis noted in control mice. The ethanol-fed mice did not control the virus replication in the liver, which was associated with a greater mononuclear cell inflammatory response, composed predominantly of cells with morphological characteristics of lymphocytes and macrophages. The early production of interferon γ, as well as production throughout the infection, was significantly lower in the ethanol-fed mice. The early production of interleukin 12 was also less in ethanol-fed mice. Conclusions The more severe hepatitis seen in the ethanol-fed mice is likely to be the result of an inability to control the growth of the virus, which is associated with a continued inflammatory response. The inability to control the virus in the liver may be related to the decreased production of interferon γ and interleukin 12.