Fluticasone Furoate Inhibits Cytokine Secretion from Nasal Epithelial Cells and Reduces Eosinophil Survival in an in vitro Model of Eosinophilic Inflammation

Abstract

Background: Fluticasone furoate (FF) is an intranasal corticosteroid indicated for the treatment of allergic rhinitis (AR). However, the anti-inflammatory effects of FF in the nasal mucosa have yet to be investigated thoroughly. The aim of this study was to investigate the effect of FF on eosinophil survival and cytokine secretion from nasal mucosa epithelial cells. Methods: Epithelial cells obtained from nasal mucosa were stimulated with 10% fetal bovine serum (FBS) in the presence of FF (from 10^-12 to 10^-7<smlcap>M</smlcap>) for 6-24 h. Cytokine [granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-8] concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated for 4 days with epithelial cell secretions in the presence or absence of FF (from 10^-12 to 10^-7<smlcap>M</smlcap>) and survival was assessed by Trypan blue dye exclusion. Results are expressed as medians of the minimum effective concentration and IC values. Results: FBS stimulated the secretion of GM-CSF, IL-6 and IL-8. FF significantly inhibited GM-CSF (up to 10^-10<smlcap>M</smlcap>, IC₂₅ = 12.6 p<smlcap>M</smlcap>), IL-6 (up to 10^-10<smlcap>M</smlcap>, IC₂₅ = 65.8 p<smlcap>M</smlcap>) and IL-8 (up to 10^-11<smlcap>M</smlcap>, IC₂₅ = 8.6 p<smlcap>M</smlcap>) secretion induced by FBS (n = 8). Epithelial cell secretions induced eosinophil survival from day 1 to day 4 (n = 6). This effect was significantly inhibited by FF (up to 10^-12<smlcap>M</smlcap>) at day 3 (IC₅₀ = 3.22 n<smlcap>M</smlcap>) and day 4 (IC₅₀ = 1.29 n<smlcap>M</smlcap>). Conclusions: The results obtained in this in vitro model suggest that FF may reduce upper airway eosinophilic inflammation through decreasing cytokine secretion from epithelial cells and reducing eosinophil survival.