Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophil apoptosis.
Inhaled glucocorticoids are widely used to treat chronic obstructive pulmonary disease without much evidence of efficiency in this disease where neutrophils may contribute to the pathophysiology. This prompted us to test the effects of several currently used inhaled and systemic glucocorticoids on human neutrophil apoptosis. Beclomethasone, budesonide, dexamethasone, fluticasone propionate, hydrocortisone and prednisolone inhibited apoptosis in a concentration-dependent manner as assessed by flow cytometric analysis, annexin-V binding and morphological analysis. The maximal inhibition of apoptosis was 50-60%. The order of potency was fluticasone propionate (EC(50) 0.6+/-0.2 nM) approximately equal to budesonide (EC(50) 0.8+/-0.2 nM)> dexamethasone approximately equal to prednisolone approximately equal to beclomethasone approximately equal to hydrocortisone. The inhibitory effects of glucocorticoids were reversed by mifepristone. Moreover, glucocorticoids slightly enhanced the inhibitory effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on neutrophil apoptosis. The present data suggests that budesonide and fluticasone propionate prolong human neutrophil survival by inhibiting apoptosis at clinically relevant drug concentrations via an effect on glucocorticoid receptor.
Zhang
X
X
Medical School, University of Tampere, Tampere, Finland.
Moilanen
E
E
Kankaanranta
H
H
D000730:Androstadienes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis; D001507:Beclomethasone / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation; D000068298:Fluticasone; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000187:drug effects
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D019819:Budesonide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000068298:Fluticasone; D001507:Beclomethasone