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

Interferon-γ (IFN-γ) is an important cytokine involved in the regulation of allergen-induced immune responses. We examined the role of IFN- γ in a Brown-Norway rat model of bronchial hyperresponsiveness (BHR) and airway 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-γ (10⁵ U/rat over 3 days, intraperitoneally)or anti-IFN-γ blocking antibody (DB-1 0.3 mg/rat, intravenously) prior to exposure to OA aerosol and were studied 18-24 hr later. In sensitized animals, OA induced significant BHR, accumulation of eosinophils, T lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid, and also increased eosinophils and CD8⁺ T cells in the airways. Exogenous IFN-γ attenuated allergen-induced BHR (P<0.02, compared with sham-treated animals) together with a significant reduction in eosinophil and neutrophil numbers in BAL fluid (P<0.005), and eosinophils and CD8⁺ T cells in airways (P<0.05). By contrast, anti-IFN-γ antibody increased airway CD4⁺ T cells and BHR. Using reverse transcriptase- polymerase chain reaction, significant increases in Th2 [interleukin-4 (IL- 4), IL-5 and IL-10], and IFN-γ cytokine mRNA were found in the lungs of sensitized and OA-exposed animals, while exogenous IFN-γ significantly suppressed IL-4, IL-5 and IL-10 mRNA expression, and anti-IFN-γ antibody increased IL-4 and IL-5 mRNA expression. These results indicate that Th1 effects, such as those mediated by IFN-γ, play a down-regulatory role to suppress the Th2 responses associated with allergen-induced BHR and eosinophilic inflammation.