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Suppression of cytokine release by fluticasone furoate vs mometasone furoate in human nasal tissue ex-vivo Zhang N; Van Crombruggen K; Holtappels G; Lan F; Katotomichelakis M; Zhang L; Hogger P; Bachert CPLoS One 2014[]; 9 (4): e93754BACKGROUND: 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.|Adult[MESH]|Aged[MESH]|Androstadienes/*pharmacology[MESH]|Anti-Inflammatory Agents/*pharmacology[MESH]|Cytokines/immunology/*metabolism[MESH]|Enterotoxins/pharmacology[MESH]|Female[MESH]|Humans[MESH]|Male[MESH]|Middle Aged[MESH]|Mometasone Furoate[MESH]|Nasal Mucosa/immunology/*metabolism[MESH]|Pregnadienediols/*pharmacology[MESH]|T-Lymphocytes, Helper-Inducer/immunology/*metabolism[MESH]|Time Factors[MESH] |
