[Inhibition of antigen-induced late asthmatic response and bronchial hyperresponsiveness by cyclosporin A]

We have previously demonstrated that Cyclosporin A (CyA), a T lymphocyte-selective immunosuppressive agent, reduced the delayed-phase bronchial eosinophil infiltration after antigen challenge in a guinea pig model of asthma. In the present study, we studied the effects of CyA on antigen-induced late asthmatic response (LAR) and bronchial hyperresponsiveness following LAR. Guinea pigs immunized by repeated exposure to aerosolized ovalbumin (OA) were intravenously given metopirone, a cortisol synthesis inhibitor, 24 hours before and 30 minutes before antigen challenge, and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. After antigen challenge with high dose of OA, LAR occurred in twelve of fifteen animals (80%) and the bronchial responsiveness to acetylcholine was significantly increased. However, when guinea pigs were treated with CyA from the beginning of immunization period, the development of LAR was completely inhibited, although similar magnitude of immediate bronchoconstriction was observed, and a subsequent increase in bronchial responsiveness was partially but significantly blocked. Since CyA has been shown to suppress activation of guinea pig T lymphocytes and their production of lymphokines, these results suggest that T cell factor(s) may be important for the elicitation of LAR and the antigen-induced bronchial hyperresponsiveness.