Inhibition of interleukin-5 mediated eosinophil viability by fluticasone 17-propionate: Comparison with other glucocorticoids

J. B. Hagan, H. Kita, G. J. Gleich

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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-γ- mediated eosinophil viability was inhibited by 1.0-1000 nM fluticasone 17- propionate, this inhibition was not overcome by increased concentrations of interferon-γ. 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)999-1006
Number of pages8
JournalClinical and Experimental Allergy
Volume28
Issue number8
DOIs
StatePublished - 1998

Keywords

  • Cytokines
  • Dexamethasone
  • Eosinophil
  • Fluticasone 17- propionate
  • Glucocorticoids
  • Granulocyte-macrophage colony-stimulating factor
  • Hydrocortisone
  • Interferon-γ
  • Interleukin (IL)-5

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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