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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-116779
  • 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 BBackground: 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.show moreshow less

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Metadaten
Author: Nan Zhang, Koen Van Crombruggen, Gabriele Holtappels, Feng Lan, Michail Katotomichelakis, Luo Zhang, Petra Högger, Claus Bachert
URN:urn:nbn:de:bvb:20-opus-116779
Document Type:Journal article
Faculties:Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie
Language:English
Parent Title (English):PLOS ONE
Year of Completion:2014
Volume:9
Issue:4
Pagenumber:e93754
Source:PLoS ONE 9(4): e93754. doi:10.1371/journal.pone.0093754
DOI:https://doi.org/10.1371/journal.pone.0093754
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24710117
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Tag:affinity; allergic rhinitis; cells; human receptor kinetics; intranasal corticosteroids; propionate; secretion; spray; staphylococcus aureus; therapy
Release Date:2015/08/06
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung