Effects of tumor necrosis factor-α treatment on mortality in murine cytomegalovirus-infected mice

Abstract

The effects of treatment with recombinant DNA-derived Tumor Necrosis Factor-α (TNF-α) in a murine model of cytomegalovirus infection were investigated. Treatment of 3-week-old Swiss Webster mice with murine TNF-α prior to infection with murine cytomegalovirus (MCMV) had no demonstrable effect on mortality. However, if mice were treated prior to infection with a combination of murine IFN-γ and murine TNF-α, the dose of IFN-γ required to achieve significant reduction in mortality was reduced by a factor > 10. In contrast to the beneficial effects of prophylactic TNF-α treatment in combination with IFN-γ, TNF-α treatment of mice after MCMV infection resulted in increased mortality. The increased mortality occurred when non-lethal doses of TNF-α were used and required virus replication. The effects of TNF-α treatment on mortality in MCMV-infected mice were not predicted from cell culture experiments which evaluated the effects of TNF-α treatment on MCMV replication in primary mouse embryo fibroblasts.