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

• Published in: The Journal of immunology (1950) Vol. 161; no. 8; pp. 4283 - 4288
• Main Authors: Shibata, Y, Foster, L A, Kurimoto, M, Okamura, H, Nakamura, R M, Kawajiri, K, Justice, J P, Van Scott, M R, Myrvik, Q N, Metzger, W J
• Format: Journal Article
• Language: English
• Published: United States 15-10-1998
• Subjects: Animals; Chitin - immunology; Immunity, Cellular; Interferon-gamma - immunology; Interleukin-10 - immunology; Killer Cells, Natural - immunology; Macrophage Activation - immunology; Macrophages - immunology; Mice
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.8.4283

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 anti-NK1.1 or anti-IFN-gamma Abs. The results established that chitin treatment of KO mice increased superoxide anion release from alveolar macrophages (Mphi) 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-gamma that is primarily responsible for this alveolar Mphi 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 Mphi, contributed to the IFN-gamma-inducing activity of chitin. Our results established that exogenous IL-10 inhibited chitin-induced IFN-gamma production in spleen cell cultures from both KO and WT mice. Exogenous IL-10 also inhibited IL-12 and TNF-alpha production by chitin-stimulated Mphi. Exogenous IL-10 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 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-gamma production. However, the inhibitory effects of endogenous IL-10 appear to be dominant in the chitin-induced alveolar Mphi priming response in vivo.