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 nonlethal 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.
Anderson
K P
KP
Department of Medicinal and Analytical Chemistry, Genentech, South San Francisco, CA 94080.
Lie
Y S
YS
Low
M A
MA
Fennie
E H
EH
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000401:mortality; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000187:drug effects / Q000254:growth & development; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma