Endogenous Interleukin-10 Produced by Antigen-Irrelevant Cells Promotes the Development of Experimental Murine Allergic Conjunctivitis

Abstract

Interleukin (IL)-10 is known to act as an immunoregulatory cytokine in both T helper cell 1 (Th1)- and Th2-mediated immune responses. Here, we ask whether IL-10 regulates the development of experimental allergic conjunctivitis (EC), a Th2-mediated inflammatory disease. Wild-type (WT) and IL-10 knockout (IL-10 KO) mice were immunized with ragweed (RW) and then repeatedly challenged with RW in eye drops. Twenty-four hours after the final challenge, conjunctivas were harvested for histological analysis, while the blood and spleens were used to determine the RW-specific immunoglobulin levels in serum and proliferation or cytokine responses and splenocyte transfer, respectively. The IL-10 KO mice had significantly less severe EC (as determined by conjunctival eosinophil infiltration) than the WT mice and evinced greater RW-specific splenocyte proliferation and cytokine production. However, the RW-specific immunoglobulin levels of the two strains did not differ. When the splenocytes from RW-primed WT mice were transferred into IL-10 KO or WT mice, the IL-10 KO mice showed significantly less conjunctival eosinophil infiltration. In contrast, when the splenocytes from RW-primed IL-10 KO or WT mice were transferred into WT mice, both splenocyte populations generated equivalent severe EC. These data indicate that IL-10 does not serve as an immunoregulatory cytokine in the development of EC. Instead, it appears that IL-10 produced by antigen-irrelevant cells acts in the effector phase to promote the development of EC.