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PLoS One. 2014 Apr 7;9(4):e93754. doi: 10.1371/journal.pone.0093754. eCollection 2014.

Suppression of cytokine release by fluticasone furoate vs. mometasone furoate in human nasal tissue ex-vivo.

Author information

  • 1Upper Airway Research Laboratory, Ghent University Hospital, Ghent, Belgium.
  • 2Department of Otorhinolaryngology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
  • 3Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, P.R.China.
  • 4Institute for Pharmacy and Food Chemistry, Julius-Maximilians-Universitity, Würzburg, Germany.
  • 5Upper Airway Research Laboratory, Ghent University Hospital, Ghent, Belgium; Division of ENT Diseases, Clintec, Karolinska Institutet, Stockholm, Sweden.

Abstract

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)-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.

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.

PMID:
24710117
[PubMed - in process]
PMCID:
PMC3977874
Free PMC Article

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