The in vivo and in vitro effects of interleukin-1 and tumor necrosis factor on murine cytomegalovirus infection.
The effects of tumor necrosis factor (TNF) and interleukin-1 (IL-1) on infection with murine cytomegalovirus (MCMV) were investigated in vitro and in 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 x 10(8) pfu to approximately 4 x 10(6) 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 these in 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 MCMV in vitro, these agents do not result in a useful therapeutic effect in 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.
van der Meer
J W
JW
Dept. Internal Medicine, University Hospital, Nijmegen, The Netherlands.
Rubin
R H
RH
Pasternack
M
M
Medearis
D N
DN
Lynch
P
P
Dinarello
C A
CA
D000305:Adrenal Cortex Hormones / Q000097:blood; D000818:Animals; D003586:Cytomegalovirus Infections / Q000628:therapy*; D005260:Female; D007375:Interleukin-1 / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha