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.

Superior effect of MP-AzeFlu than azelastine or fluticasone propionate alone on reducing inflammatory markers

“…In the present study, the corticosteroid FP and the formulation MP-AzeFlu reduced IL-6 and GM-CSF secretions from nasal mucosa epithelial cells relative to FBS. This is consistent with previous findings for the intranasal corticosteroids budesonide, beclomethasone dipropionate, mometasone furoate, FP, and fluticasone furoate [23, 24, 29, 30, 35]. In this study, MP-AzeFlu findings for IL-8, GM-CSF, and sICAM-1 differed little from FP alone.…”

“…In this study, MP-AzeFlu findings for IL-8, GM-CSF, and sICAM-1 differed little from FP alone. We also found that FP and MP-AzeFlu reduced eosinophil survival relative to HECM, consistent with previous findings for intranasal corticosteroids [24, 29, 30].…”

Corticosteroid treatment regulates mucosal remodeling in chronic rhinosinusitis with nasal polyps

“…In a previous study, Mastruzzo et al reported a decreased number of eosinophils in NP tissue after an 8‐week treatment with budesonide. These observations are expected because it is well known that CS reduces the infiltration and survival of eosinophils by inducing apoptosis and by inhibiting the response to survival signals such as interleukin 5 and granulocyte/macrophage colony‐stimulating factor…”

Modulation of Allergic Inflammation in the Nasal Mucosa of Allergic Rhinitis Sufferers With Topical Pharmaceutical Agents

“…Epithelial generated cytokines act as chemoattractants and recruit effector cells such as eosinophils, basophils and T cells to the nasal mucosa. Treatment with fluticasone propionate or fluticasone furoate significantly reduced levels of GM-CSF, IL-6 and IL-8 in stimulated nasal epithelial cells (Ohnishi et al, 1994; Smith et al, 2002; Mullol et al, 2014). In stimulated murine mast cells, fluticasone propionate was shown to inhibit the release of IL-4, IL-6, IL-8 and TNF-α at an IC 50 of <1 nM (Fuller et al, 1995).…”