Role of IFN-gamma in the Inhibition of the Allergic Airway Inflammation Caused by IL-12

• Published in: American journal of respiratory cell and molecular biology Vol. 17; no. 6; pp. 767 - 771
• Main Authors: Brusselle, Guy G, Kips, Johan C, Peleman, Renaat A, Joos, Guy F, Devos, Rene R, Tavernier, Jan H, Pauwels, Romain A
• Format: Journal Article
• Language: English
• Published: United States Am Thoracic Soc 01.12.1997
• Subjects: Animals; Bronchoalveolar Lavage Fluid - cytology; Crosses, Genetic; Interferon-gamma - physiology; Interleukin-12 - toxicity; Mice; Mice, Inbred C57BL; Recombinant Proteins - toxicity; Respiratory Hypersensitivity - chemically induced; Respiratory Hypersensitivity - pathology; Respiratory Hypersensitivity - prevention & control
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/ajrcmb.17.6.2820

T-helper 2 (Th2)-like cells are thought to play a crucial role in the pathogenesis of the eosinophilic airway inflammation observed in asthma. In a murine model of allergen-induced airway eosinophilia and bronchial hyperresponsiveness (BHR), we have shown that interleukin (IL)-12 can suppress antigen-induced airway changes despite the presence of circulating specific IgE. In the present study, we investigated the role of interferon-gamma (IFN-gamma) in the inhibitory effects of IL-12 on allergic airway inflammation. Repeated daily exposure of actively immunized mice to aerosolized ovalbumin (OVA), as compared with aerosolized saline (SAL), induced a significant increase in bronchoalveolar lavage fluid (BALF) eosinophilia and OVA-specific serum IgE in both IFN-gamma-receptor-deficient (IFN-gammaR KO) and wild-type mice. As compared with placebo (PLAC), administration of recombinant murine IL-12 (rmIL-12) during the daily aerosol exposure (but not at the time of immunization) significantly inhibited BALF eosinophilia in both IFN-gammaR KO mice and wild-type controls, without influencing the production of specific IgE. In contrast, administration of rmIL-12 during the active immunization inhibited both BALF eosinophilia and specific IgE in wild-type mice as compared with littermates given PLAC; however, treatment with rmIL-12 during immunization, in comparison with PLAC, caused a significant increase in BALF eosinophilia and specific IgE in IFN-gammaR KO mice. These results demonstrate that inhibition of the allergen-induced eosinophil influx in murine airways by IL-12 is IFN-gamma-dependent during the initial sensitization, but becomes IFN-gamma-independent during the secondary response.