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 (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.
Zhang
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X
Medical School, FIN-33014, University of Tampere, Tampere, Finland.
Moilanen
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E
Kankaanranta
H
H
D000730:Androstadienes / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001507:Beclomethasone / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects*; D000068298:Fluticasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D015735:Mifepristone; D019819:Budesonide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000068298:Fluticasone; D001507:Beclomethasone