Abstract
Earlier studies showed that tumor necrosis factor (TNF) exerts a mitogenic effect in human diploid fibroblasts. Here we demonstrate that purified E. coliderived recombinant human TNF inhibits encephalomyocarditis virus replication in “aged” human fibroblasts. Addition of neutralizing antibodies to human beta interferon (IFN-β) blocked the antiviral action of TNF, indicating that this action is mediated by the generation of IFN-β. We also show that antiserum to IFN-β enhanced the mitogenic effect of TNF in confluent, serum-starved human fibroblasts, suggesting that induction of IFN-β by TNF represents a physiological negative feedback mechanism regulating cell proliferation. Blot hybridization analysis of cytoplasmic polyadenylated RNA showed that TNF induced IFN- β 2 mRNA, whereas no induction of IFN- β 1 mRNA could be demonstrated. The results suggest that IFN- β 2 has biological functions distinct from the other interferons.
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