INTERLEUKIN-12 PREVENTS ANTIGEN-INDUCED EOSINOPHIL RECRUITMENT INTO MOUSE AIRWAYS

Interleukin-12 (IL-12) is a key cytokine that promotes Th1-type cell-m ediated immunity and inhibits Th2-type responses. We have previously s hown that antigen-induced eosinophil recruitment into the airways of s ensitized mice is mediated by Th2-type CD4(+) T cells that produce IL- 5. Therefore, to determine whether IL-12 regulates antigen-induced eos inophil recruitment into the airways, we studied the effect of recombi nant 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 (B ALF) 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 rI L-12 suppressed IL-5 levels but enhanced IFN-gamma levels in the BALF of the mice after antigen inhalation. The administration of rIL-12 als o decreased in vitro antigen-induced IL-4 and IL-5 production, but not IFN-gamma production, in spleen cells of the mice. Furthermore, pretr eatment with anti-IFN-gamma monoclonal antibody prevented the IL-12 in hibition of antigen-induced eosinophil infiltration into the tracheas of the mice. These results indicate that IL-12 downregulates antigen-i nduced eosinophil recruitment into the airways by inhibiting IL-5 prod uction in sensitized animals.