Thein vivo andin vitro effects of interleukin-1 and tumor necrosis factor on murine cytomegalovirus infection

Abstract

The effects of tumor necrosis factor (TNF) and interleukin-1 (IL-1) on infection with murine cytomegalovirus (MCMV) were investigatedin vitro andin vivo. The addition of each of these cytokines (at 1 ng/ml) to tissue culture monolayers 24 hr prior to MCMV challenge produced a reproducible decrease in vital titer (from 1 × 10⁸ pfu to approximately 4 × 10⁶ pfu for both cytokines). There was no further increase in this effect when a 10 or 100 ng/ml of each of these cytokines was employed. Despite thesein vitro effects, the pretreatment of suckling, weanling, or adult mice with 80 or 400 ng of TNF or IL-1 alone, or 80 ng of each cytokine together, had no effect on the survival of mice following MCMV. Similarly, neither of these cytokines adversely influenced the protective effects of hyperimmune anti-MCMV antiserum; that is, they did not attenuate the protection conferred by the antiserum nor affect the protective effects of subtherapeutic doses of the antiserum. We conclude that despite promising antiviral effects against MCMVin vitro, these agents do not result in a useful therapeutic effectin vivo. Moreover, despite the ability of IL-1 to induce ACTH and corticosterone in mice, IL-1 treatment did not increase the mortality to CMV.