Inhibition of interleukin-5 mediated eosinophil viability by fluticasone 17-propionate: comparison with other glucocorticoids.
BACKGROUND
Inhaled glucocorticoids are commonly employed to treat patients with asthma. Eosinophils are important effector cells in the pathogenesis of asthma, and, in vitro, glucocorticoids modulate eosinophil viability.


OBJECTIVE
Using this glucocorticoid inhibition of eosinophil viability, we compared the in vitro potencies of several inhaled glucocorticoids with particular attention to fluticasone 17-propionate.


METHODS
Eosinophils from normal or mildly atopic donors were purified, cultured with cytokines and glucocorticoids, and on day 4, after staining with propidium iodide, analysed by flow cytometry.


RESULTS
Eosinophil viability was prolonged by interleukin (IL)-5 in a concentration-dependent manner; in contrast, dexamethasone inhibited the IL-5 effect. Fluticasone 17-propionate, 1.0-1000 nM, also inhibited the IL-5 effect in a concentration-dependent manner; interestingly, at 0.1 nM fluticasone 17-propionate modestly, but significantly, enhanced eosinophil survival. High concentrations of IL-5 and granulocyte-macrophage colony-stimulating factor essentially completely overcame the inhibitory effect of 1000 nM fluticasone 17-propionate on eosinophil survival. In contrast, although interferon-gamma-mediated eosinophil viability was inhibited by 1.0-1000 nM fluticasone 17-propionate, this inhibition was not overcome by increased concentrations of interferon-gamma. Comparison of the glucocorticoid inhibition of eosinophil viability in the presence of 10 pg/mL IL-5 resulted in these drug IC50 values (in nM): fluticasone 17-propionate, 1.3; budesonide, 8.5; triamcinolone acetonide, 25; flunisolide, 32; dexamethasone, 94; beclomethasone 17-monopropionate, 210; beclomethasone 17,21-dipropionate, 290; and hydrocortisone, >1000.


CONCLUSIONS
Fluticasone 17-propionate's effect on cytokine-mediated eosinophil viability is similar qualitatively to other glucocorticoid preparations. However, quantitatively, fluticasone 17-propionate has the most potent suppressive effects on IL-5 mediated eosinophil viability among the currently available inhaled glucocorticoids in the United States.
Hagan
J B
JB
Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Kita
H
H
Gleich
G J
GJ
D000280:Administration, Inhalation; D000730:Androstadienes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects*; D005434:Flow Cytometry; D000068298:Fluticasone; D006801:Humans; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D015848:Interleukin-5; D000068298:Fluticasone