GAMMA-INTERFERON MODIFIES GUINEA-PIG AIRWAY FUNCTIONS IN-VITRO

Cytokines produced by T-lymphocytes may have significant roles in the airway inflammation seen in bronchial asthma. Gamma interferon IFN-gamma), a T-cell derived cytokine, is known to modify functions of both immune and non-immune cells. In this study, we investigated whether IFN-gamma can modify guinea pig airway functions in vivo. The isometric tension of guinea pig airway strips was measured in a tissue bath filled with Krebs-Henseleit solution. Contracting responses to carbachol and KCl, and the relaxing response to isoproterenol (ISO) were examined. Effects of IFN-gamma were examined by comparing responses of the strips incubated with or without IFN-gamma (1000 U.ml(-1); 25,000 U.ml(-1). Contracting responses to carbachol and KCl were not affected by the incubation with IFN-gamma other than slight increased in maximum contraction by carbachol after 5 hours incubation with 25,000 U.ml(-1) of IFN-gamma. Both 1 and 5 h incubation of strips with 25,000 U.ml(-1) IFN-gamma significantly increased the sensitivity to ISO (p < 0.01 and p < 0.05, respectively) without affecting maximum relaxation. The effect of IFN-gamma on ISO relaxation was abolished by the denudation of airway epithelium from strips, indomethacin (2 mu M), and cycloheximide (70 mu M) but not by N infinity-nitro-L-arginine methyl ester (30 mu M). In addition, heat-inactivated INF-gamma and bacterial endotoxin (LPS, 0.625 pg.ml(-1) had no effect on ISO relaxation. These results suggest that IFN-gamma is able to modify airway smooth muscle response to beta-adrenergic agonist by inducing release of prostanoids from airway epithelium.