Inhibitory effects of endogenous and exogenous interferon-gamma on bronchial hyperresponsiveness, allergic inflammation and T-helper 2 cytokines in Brown-Norway rats

Interferon-gamma (IFN-gamma) is an important cytokine involved in the regul ation of allergen-induced immune responses. We examined the role of IFN-gam ma in a Brown-Norway rat model of bronchial hyperresponsiveness (BHR) and a irway eosinophilia, and its effects on the mRNA expression of T helper type 1 (Th1)/Th2 cytokine. Ovalbumin (OA)-sensitized animals were given either exogenous IFN-gamma (10(5) U/rat over 3 days, intraperitoneally) or anti-IF N-gamma blocking antibody (DB-1 0 . 3 mg/rat, intravenously) prior to expos ure to OA aerosol and were studied 18-24 hr later. In sensitized animals, O A induced significant BHR, accumulation of eosinophils, T lymphocytes and n eutrophils in bronchoalveolar lavage(BAL) fluid, and also increased eosinop hils and CD8(+) T cells in the airways. Exogenous IFN-gamma attenuated alle rgen-induced BHR (P < 0 . 02, compared with sham-treated animals) together with a significant reduction in eosinophil and neutrophil numbers in BAL fl uid (P < 0 . 005), and eosinophils and CD8(+) T cells in airways (P < 0 . 0 5). By contrast, anti-IFN-gamma antibody increased airway CD4(+) T cells an d BHR. Using reverse transcriptase-polymerase chain reaction, significant i ncreases in Th2 [interleukin-4 (IL-4), IL-5 and IL-10], and IFN-gamma cytok ine mRNA were found in the lungs of sensitized and OA-exposed animals, whil e exogenous IFN-gamma significantly suppressed IL-4, IL-5 and IL-10 mRNA ex pression, and anti-IFN-gamma antibody increased IL-4 and IL-5 mRNA expressi on. These results indicate that Th1 effects, such as those mediated by IFN- gamma, play a down-regulatory role to suppress the Th2 responses associated with allergen-induced BHR and eosinophilic inflammation.