IMMUNOREGULATORY ROLES OF IL-10 IN INNATE IMMUNITY - IL-10 INHIBITS MACROPHAGE PRODUCTION OF IFN-GAMMA-INDUCING FACTORS BUT ENHANCES NK CELL PRODUCTION OF IFN-GAMMA

In our study of the immunoregulatory roles of IL-10 in innate immunity , nonantigenic phagocytosable chitin particles were administered i.v. to IL-10-deficient (knockout (KO)) mice or KO mice pretreated with ant i-NK1.1 or anti-IFN-gamma Abs. The results established that chitin tre atment of KO mice increased superoxide anion release from alveolar mac rophages (M phi) to a level much higher than that in wild-type (WT) mi ce. The results also suggested that the NK cell is the source of IFN-g amma that is primarily responsible for this alveolar M phi priming. To further study the roles of IL-10-inhibiting chitin-induced IFN-gamma production, we used spleen cell cultures, The experiments showed that IL-12, IL-18, and TNF-alpha, which were produced by chitin-stimulated M phi, contributed to the IFN-gamma-inducing activity of chitin, Our r esults established that exogenous IL-10 inhibited chitin-induced IFN-g amma production in spleen cell cultures from both KO and WT mice. Exog enous IL-10 also inhibited IL-12 and TNF-alpha production by chitin-st imulated M phi. Exogenous IL-IO decreased IL-12- or IL-18-induced IFN- gamma levels in KO but not in WT NK cell cultures. However, exogenous IL-10 enhanced IFN-gamma levels when NK cells were stimulated simultan eously with both IL-12 and IL-18 in KO and WT cultures. Our in vitro d ata indicate that IL-IO has differential effects on chitin-induced IFN -gamma production. However, the inhibitory effects of endogenous IL-10 appear to be dominant in the chitin-induced alveolar M phi priming re sponse in vivo.