INTERLEUKIN-12 PRODUCTION BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES

Human polymorphonuclear leukocytes (PMN) stimulated by lipopolysacchar ide (LPS) produce interleukin-12 (IL-12). Both the free IL-12 p40 chai n and minute amounts of the biologically active IL-12 p70 heterodimers are produced by PMN. Interferon-gamma (IFN-gamma) enhanced the LPS-in duced secretion of both the free IL-12 p40 chain and the p70 heterodim er by approximately fivefold. As observed for other IL-12-producing ce ll types, the ratio of free p40 chain to p70 heterodimer secreted by L PS-stimulated PMN was approximately 20:1. LPS induced a 100-fold incre ase of IL-12 p40 mRNA, but had minimal effect on p35 mRNA accumulation . IFN-gamma enhanced the LPS-induced accumulation of p40 mRNA and dire ctly induced a several-fold increase in the accumulation of p35 mRNA. Therefore, the combined effect of LPS and IFN-gamma induced sufficient expression of both p40 and p35 to attain production of the biological ly active p70 heterodimer at physiologically relevant concentrations. The ratio between p40 and p35 mRNA abundance in PMN stimulated with bo th LPS and IFN-gamma, was approximately 200:1, explaining the secretio n of the free p40 chain in much higher concentrations than the p70 het erodimer, IL-10, an inhibitor of the production of various cytokines i n PMN, also suppressed IL-12 mRNA accumulation and secretion by PMN. B ecause of the important immunoregulatory function of IL-12, in particu lar induction of IFN-gamma production and facilitation of T helper cel l type 1 response, the ability of PMN to produce IL-12 suggests that n eutrophils may play an active role in the regulatory interaction betwe en innate resistance and adaptive immunity.