Interleukin-1 Can Inhibit Interferon-β Synthesis and Its Antiviral Action: Comparison with Tumor Necrosis Factor

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Abstract
Earlier studies showed that both tumor necrosis factor (TNF) and interleukin-1 (IL1) can inhibit virus replication in cultured cells. However, in human FS-4 fibroblasts, in which recombinant human TNF protected cells from encephalomyocarditis (EMC) virus infection, recombinant human IL1α and IL1β failed to induce antiviral protection. Moreover, both forms of IL1 inhibited the development of the TNF-induced antiviral state. To elucidate the mechanism of this inhibition, we examined the effect of IL1 on the synthesis of interferon-β (IFN-β), stimulated with polyinosinate · polycytidylate [poly(I) · poly(C)]. When added 2 h or more before poly(I) · poly(C), both forms of IL1 had a strong inhibitory effect on IFN-β synthesis, as determined by antiviral assay of the IFN-β protein or by quantitation of IFN-β mRNA levels in Northern blot analysis. However, when IL1 was added simultaneously with poly(I) · poly(C), or 2 h after poly (I) · poly (C), IFN-β synthesis was increased. The inhibitory action of IL1 on poly (I) · poly(C)-induced IFN-β synthesis was abolished in the presence of cycloheximide, suggesting that it is mediated indirectly by an IL1-induced product in the FS-4 cells. In addition to its ability to inhibit IFN-β synthesis, IL1 also caused a partial reversal of the antiviral action of IFN-β. In contrast to IL1, TNF did not inhibit IFN-β synthesis, nor did it interfere with the antiviral action of IFN-β. Simultaneous addition of TNF and poly(I) · poly(C) to FS-4 cells enhanced IFN-β synthesis. Under proper conditions TNF and IFN-β showed an additive antiviral effect.