Impairment of antiviral cytokine expression and enhancement of Murine Cytomegalovirus (MCMV) mediated liver injury in a diabetic mouse model

Abstract

Impact of diabetes on the development of anti-viral immunity and viral pathogenesis using MCMV infection model was examined. Transgenic OVE26 mice having chronic type 1 diabetes and age matched wild type mice were infected with 2.5 X 105 PFU of MCMV per mouse via the intra-peritoneal route and were sacrificed at 36 h or 5 days post-infection. Serum levels of interleukin 12 (IL-12), interferon gamma (IFN-γ), and TNF-α, which play a critical role in activating and co-coordinating an effective early antiviral adaptive immune response, were measured at 36 h. The expression of IL-12, IFN-γ and TNF-α was markedly suppressed in diabetic mice. Additionally, examination of the in vitro immune cell function showed that splenocytes from diabetic mice also had markedly decreased IL-12 and TNF-α expression. In correspondence with decreased antiviral cytokine responses, the diabetic mice showed substantive viral replication and growth in both the spleen and liver. Consequently, the diabetic mice developed severe viral hepatitis characterized by enhanced ALT, hepatic steatosis and lesions, resulting in significant morbidity and mortality. These data strongly indicate that the diabetic state can considerably diminish the protective antiviral cytokine expression which may play a significant role in the increased severity and risk of complications of viral infections in diabetic patients.