INHIBITORY EFFECT OF INTERLEUKIN-10 ON HUMAN-LEUKOCYTE INTERFERON-ALPHA PRODUCTION BY SENDAI VIRUS

Treatment of human peripheral blood leukocytes (hPBL) with Sendai viru s induces significant production of human interferon-alpha (IFN-alpha) . Addition of human recombinant interleukin-10 (IL-10) to hPBL in vitr o prior to treatment with Sendai virus resulted in considerable inhibi tion of IFN-alpha production. Downregulation of IFN-alpha production w as IL-10 concentration-dependent and observed at IL-10 concentrations of as low as 0.05 ng/ml, with a median effective dose (ED50) of about 5 ng/ml. Inhibition of IFN-alpha production by IL-10 occurred at an ea rly stage of Sendai virus induction. The inhibitory effect of IL-10 on leukocyte interferon production was specific and blocked by pretreatm ent with neutralizing polyclonal anti-IL-10 antibody. This downregulat ory effect is at the transcriptional level, since IL-10 inhibits IFN-a lpha mRNA accumulation upon Sendai virus treatment. These data suggest that leukocyte IFN-alpha production is a highly regulated process tha t is modulated by cytokines such as IL-10 during early immunological r esponse to infection.