Suppression of Cytokine Release by Fluticasone Furoate vs. Mometasone Furoate in Human Nasal Tissue Ex-Vivo

Nan Zhang,Koen Van Crombruggen,Luo Zhang,Feng Lan,Claus Bachert,Michail Katotomichelakis,Gabriele Holtappels,Petra Högger

doi:10.1371/journal.pone.0093754

Abstract

BackgroundTopical glucocorticosteroids are the first line therapy for airway inflammation. Modern compounds with higher efficacy have been developed, but head-to-head comparison studies are sparse.ObjectiveTo compare the activity of two intranasal glucocorticoids, fluticasone furoate (FF) and mometasone furoate (MF) with respect to the inhibition of T helper (Th)1, Th2 and Th17 cytokine release in airway mucosa.MethodsWe used an ex-vivo human nasal mucosal tissue model and employed pre- and post- Staphylococcus aureus enterotoxin B (SEB)-challenge incubations with various time intervals and drug concentrations to mimic typical clinical situations of preventive or therapeutic use.ResultsAt a fixed concentration of 10−10 M, FF had significantly higher suppressive effects on interferon (IFN)-γ, interleukin (IL)-2 and IL-17 release, but not IL-5 or tumor necrosis factor (TNF)-α, vs. MF. While the maximal suppressive activity was maintained when FF was added before or after tissue stimulation, the cytokine suppression capacity of MF appeared to be compromised when SEB-induced cell activation preceded the addition of the drug. In a pre-challenge incubation setting with removal of excess drug concentrations, MF approached inhibition of IL-5 and TNF-α after 6 and 24 hours while FF maximally blocked the release of these cytokines right after pre-incubation. Furthermore, FF suppressed a wider range of T helper cytokines compared to MF.ConclusionThe study demonstrates the potential of our human mucosal model and shows marked differences in the ability to suppress the release of various cytokines in pre- and post-challenge settings between FF and MF mimicking typical clinical situations of preventive or therapeutic use.

Highlights

Topical glucocorticosteroids (GCS) are the first line therapy for allergic rhinitis, sinusitis and nasal polyposis [1,2]
To optimally respond to the expectations of the patients, a nasal topical corticosteroid should have a fast onset of action, which requires a fast uptake and strong binding to the glucocorticoid receptor, translocation of the glucocorticoid receptor complex into the nucleus and interaction with glucocorticoid response elements (GREs), resulting in a long duration of action allowing for once daily application, and a high efficacy in suppressing the local inflammation with a broad panel of cytokines from Th1, Th2 and Th17 cells included [8]
The suppressive effect of fluticasone furoate (FF) is superior to mometasone furoate (MF)

Summary

Introduction

Topical glucocorticosteroids (GCS) are the first line therapy for allergic rhinitis, sinusitis and nasal polyposis [1,2]. GCS compounds with higher efficacy and less systemic bioavailability have been developed, with fluticasone furoate (FF) as the latest compound being introduced to the market [3,4]. In absence of head-to-head comparison studies for both drugs, such comparison may be extrapolated from ex-vivo human nasal mucosal models using diseased and control mucosa with different stimuli. Topical glucocorticosteroids are the first line therapy for airway inflammation. Modern compounds with higher efficacy have been developed, but head-to-head comparison studies are sparse

Methods

Results

Conclusion