EFFECTS OF RAPAMYCIN, CYCLOSPORINE-A, AND DEXAMETHASONE ON INTERLEUKIN 5-INDUCED EOSINOPHIL DEGRANULATION AND PROLONGED SURVIVAL

Interleukin-5 (IL-5) enhances eosinophil degranulation and prolongs eo sinophil survival. Rapamycin, cyclosporin A, and dexamethasone have be en shown to influence either cytokine transcription, cytokine-mediated signalling, or degranulation by granulocytes. The study aimed to dete rmine whether these agents inhibited IL-5-enhanced eosinophil survival or degranulation. Peripheral blood eosinophils were isolated from ato pic subjects. The effects of serial dilutions (10(-6)-10(-9) M) of the se drugs or vehicle control on 1) the viability of eosinophils culture d (1-5 days) in the presence and absence of recombinant human IL-5, as measured by propidium iodide staining and flow cytometry, and 2) degr anulation of eosinophils preincubated (45 min) with rhIL-5 or medium c ontrol, as measured by eosinophil cationic protein (ECP) release after stimulation with serum-coated Sephadex beads, were assessed. Dexameth asone and rapamycin produced significant, concentration-dependent inhi bition of IL-5-enhanced eosinophil survival at pharmacologic concentra tions, whereas cyclosporin A did not. Prior incubation of eosinophils with IL-5, as compared with medium control, significantly enhanced ECP release by eosinophils on subsequent exposure to serum-coated Sephade x beads. Cyclosporin A and rapamycin significantly inhibited IL-5-enha nced ECP release in a concentration-dependent fashion, whereas dexamet hasone did not. All three drugs had no significant effect on eosinophi l survival and degranulation in the absence of IL-5. Our results sugge st that immunosuppressive drugs may inhibit IL-5-mediated mechanisms i n eosinophils which result in enhanced survival and release of granule contents. These findings may be relevant to the further development o f therapeutic strategies in allergic diseases.