Immunoregulatory Roles of IL-10 in Innate Immunity: IL-10 Inhibits Macrophage Production of IFN-γ-Inducing Factors but Enhances NK Cell Production of IFN-γ

Abstract

AbstractIn 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 anti-NK1.1 or anti-IFN-γ Abs. The results established that chitin treatment of KO mice increased superoxide anion release from alveolar macrophages (Mφ) to a level much higher than that in wild-type (WT) mice. The results also suggested that the NK cell is the source of IFN-γ that is primarily responsible for this alveolar Mφ priming. To further study the roles of IL-10-inhibiting chitin-induced IFN-γ production, we used spleen cell cultures. The experiments showed that IL-12, IL-18, and TNF-α, which were produced by chitin-stimulated Mφ, contributed to the IFN-γ-inducing activity of chitin. Our results established that exogenous IL-10 inhibited chitin-induced IFN-γ production in spleen cell cultures from both KO and WT mice. Exogenous IL-10 also inhibited IL-12 and TNF-α production by chitin-stimulated Mφ. Exogenous IL-10 decreased IL-12- or IL-18-induced IFN-γ levels in KO but not in WT NK cell cultures. However, exogenous IL-10 enhanced IFN-γ levels when NK cells were stimulated simultaneously with both IL-12 and IL-18 in KO and WT cultures. Our in vitro data indicate that IL-10 has differential effects on chitin-induced IFN-γ production. However, the inhibitory effects of endogenous IL-10 appear to be dominant in the chitin-induced alveolar Mφ priming response in vivo.