ROLE OF IFN-GAMMA IN THE INHIBITION OF THE ALLERGIC AIRWAY INFLAMMATION CAUSED BY IL-12

T-helper 2 (Th2)-like cells are thought to play a crucial role in the pathogenesis of the eosinophilic airway inflammation observed in asthm a. In a murine model of allergen-induced airway eosinophilia and bronc hial hyperresponsiveness (BHR), we have shown that interleukin (IL)-12 can suppress antigen-induced airway changes despite the presence of c irculating specific IgE. In the present study, we investigated the rol e of interferon-gamma (IFN-gamma) in the inhibitory effects of IL-12 o n allergic airway inflammation. Repeated daily exposure of actively im munized mice to aerosolized ovalbumin (OVA), as compared with aerosoli zed saline (SAL), induced a significant increase in bronchoalveolar la vage fluid (BALF) eosinophilia and OVA-specific serum IgE in both IFN- gamma-receptor-deficient (IFN-gamma R KO) and wild-type mice. As compa red with placebo (PLAC), administration of recombinant murine IL-12 (r mIL-12) during the daily aerosol exposure (but not at the time of immu nization) significantly inhibited BALF eosinophilia in both IFN-gamma R KO mice and wild-type controls, without influencing the production o f specific IgE. In contrast, administration of rmIL-12 during the acti ve immunization inhibited both BALF eosinophilia and specific IgE in w ild-type mice as compared with littermates given PLAC; however, treatm ent with rmIL-12 during immunization, in comparison with PLAC, caused a significant increase in BALF eosinophilia and specific IEE in IFN-ga mma R KO mice. These results demonstrate that inhibition of the allerg en-induced eosinophil influx in murine airways by IL-12 is IFN-gamma-d ependent during the initial sensitization, but becomes IFN-gamma-indep endent during the secondary response.