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


CONCLUSIONS
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.
Upper Airway Research Laboratory, Ghent University Hospital, Ghent, Belgium.
Nan
N
Zhang
Upper Airway Research Laboratory, Ghent University Hospital, Ghent, Belgium.
Koen
K
Van Crombruggen
Upper Airway Research Laboratory, Ghent University Hospital, Ghent, Belgium.
Gabriele
G
Holtappels
Upper Airway Research Laboratory, Ghent University Hospital, Ghent, Belgium.
Feng
F
Lan
Department of Otorhinolaryngology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Michail
M
Katotomichelakis
Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, P.R.China.
Luo
L
Zhang
Institute for Pharmacy and Food Chemistry, Julius-Maximilians-Universitity, Würzburg, Germany.
Petra
P
Högger
Upper Airway Research Laboratory, Ghent University Hospital, Ghent, Belgium; Division of ENT Diseases, Clintec, Karolinska Institutet, Stockholm, Sweden.
Claus
C
Bachert
D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068656:Mometasone Furoate; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism*; D011244:Pregnadienediols / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004768:Enterotoxins; D011244:Pregnadienediols; D000068656:Mometasone Furoate; C031818:enterotoxin B, staphylococcal; C523187:fluticasone furoate