Enhancement of human eosinophil apoptosis by fluticasone propionate, budesonide, and beclomethasone

Beclomethasone, budesonide, dexamethasone, and fluticasone propionate enhanced human eosinophil apoptosis in a concentration-dependent manner in vitro as assessed by flow cytometric analysis and morphological analysis. The order of potency was fluticasone propionate (EC50 3.7 +/- 1.8 nM) = budesonide (EC50 5.0 +/- 1.7 nM) > beclomethasone (EC50 51 +/- 19 nM) > dexamethasone (EC50 303 +/- 40 nM). Hydrocortisone, prednisolone, and prednisone (up to 1 muM) did not induce any significant increase in eosinophil apoptosis. The apoptosis promoting effects of glucocorticoids on eosinophils were reversed by an antagonist of glucocorticoid receptor mifepristone. The survival-prolonging effect of tumor necrosis factor (TNF)-alpha was reversed by dexamethasone and fluticasone (1 muM). In contrast, fluticasone, and dexamethasone (1 muM) did not reverse the survival-prolonging effects of interleukins-3 and -5 or granulocyte-macrophage colony-stimulating factor (GM-CSF). The results suggest that fluticasone and budesonide induce eosinophil apoptosis at clinically achievable drug concentrations via an effect on glucocorticoid receptor. (C) 2000 Elsevier Science B.V. All rights reserved.