I Iwamoto, K Kumano, M Kasai, K Kurasawa and A Nakao
Department of Internal Medicine, Chiba University School of Medicine, Japan.

Interleukin-12 (IL-12) is a key cytokine that promotes Th1-type cell- mediated immunity and inhibits Th2-type responses. We have previously shown that antigen-induced eosinophil recruitment into the airways of sensitized mice is mediated by Th2-type CD4+ T cells that produce IL-5. Therefore, to determine whether IL-12 regulates antigen-induced eosinophil recruitment into the airways, we studied the effect of recombinant murine IL-12 on antigen-induced eosinophil infiltration into the tracheas of sensitized mice, and also the effect of IL-12 on IL-5 and interferon-gamma (IFN-gamma) levels in bronchoalveolar lavage fluid (BALF) from the mice. The intraperitoneal administration of recombinant IL-12 (rIL-12) inhibited antigen-induced eosinophil infiltration into the mouse trachea in a dose-dependent manner. The administration of rIL-12 suppressed IL-5 levels but enhanced IFN-gamma levels in the BALF of the mice after antigen inhalation. The administration of rIL-12 also decreased in vitro antigen-induced IL-4 and IL-5 production, but not IFN-gamma production, in spleen cells of the mice. Furthermore, pretreatment with anti-IFN-gamma monoclonal antibody prevented the IL-12 inhibition of antigen-induced eosinophil infiltration into the tracheas of the mice. These results indicate that IL-12 downregulates antigen-induced eosinophil recruitment into the airways by inhibiting IL-5 production in sensitized animals.

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