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 (EC(50) 3.7+/-1.8 nM) approximately budesonide (EC(50) 5.0+/-1.7 nM)>beclomethasone (EC(50) 51+/-19 nM)>dexamethasone (EC(50) 303+/-40 nM). Hydrocortisone, prednisolone, and prednisone (up to 1 microM) 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 microM). In contrast, fluticasone, and dexamethasone (1 microM) 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.