TY - JOUR A1 - Zhang, Nan A1 - Van Crombruggen, Koen A1 - Holtappels, Gabriele A1 - Lan, Feng A1 - Katotomichelakis, Michail A1 - Zhang, Luo A1 - Högger, Petra A1 - Bachert, Claus T1 - Suppression of Cytokine Release by Fluticasone Furoate vs. Mometasone Furoate in Human Nasal Tissue Ex-Vivo T2 - PLOS ONE N2 - Background: 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. Objective: To 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. Methods: We 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. Results: At a fixed concentration of 10(-10) M, FF had significantly higher suppressive effects on interferon (IFN)-gamma,interleukin (IL)-2 and IL-17 release, but not IL-5 or tumor necrosis factor (TNF)-alpha, 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-alpha 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. Conclusion: The 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. KW - allergic rhinitis KW - human receptor kinetics KW - staphylococcus aureus KW - intranasal corticosteroids KW - cells KW - propionate KW - secretion KW - affinity KW - therapy KW - spray Y1 - 2014 UR - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/11677 UR - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-116779 VL - 9 IS - 4 ER -