EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA TREATMENT ON MORTALITY IN MURINE CYTOMEGALOVIRUS-INFECTED MICE

The effects of treatment with recombinant DNA-derived Tumor Necrosis Factor-alpha (TNF-alpha) in a murine model of cytomegalovirus infection were investigated. Treatment of 3-week-old Swiss Webster mice with murine TNF-alpha 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-gamma and murine TNF-alpha, the dose of IFN-gamma required to achieve significant reduction in mortality was reduced by a factor > 10. In contrast to the beneficial effects of prophylactic TNF-alpha treatment in combination with IFN-gamma, TNF-alpha treatment of mice after MCMV infection resulted in increased mortality. The increased mortality occurred when non-lethal doses of TNF-alpha were used and required virus replication. The effects of TNF-alpha treatment on mortality in MCMV-infected mice were not predicted from cell culture experiments which evaluated the effects of TNF-alpha treatment on MCMV replication in primary mouse embryo fibroblasts.