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Dupilumab prevents nasal epithelial function alteration by IL-4 in vitro: Evidence for its efficacy.
- Source :
-
International forum of allergy & rhinology [Int Forum Allergy Rhinol] 2024 Aug; Vol. 14 (8), pp. 1337-1349. Date of Electronic Publication: 2024 Mar 11. - Publication Year :
- 2024
-
Abstract
- Background: Chronic rhinosinusitis with nasal polyp (CRSwNP) is a typical type 2 inflammation involving interleukin (IL)-4 and IL-13. Dupilumab is a fully human monoclonal antibody targeting IL-4 receptor α subunit, thereby blocking signaling by both cytokines. Our hypothesis was that IL-4 and IL-13, by inducing a severe epithelial dysregulation, are involved in CRSwNP pathogenesis. This study aimed to evaluate the in vitro direct effect of IL-4, IL-13, and dupilumab on nasal epithelial functions.<br />Methods: Nasal polyps and control mucosa from 28 patients, as well as human nasal epithelial cells (HNEC) from 35 patients with CRSwNP were used. Three major epithelial functions were investigated: the epithelial barrier function (characterized by transepithelial electrical resistance measurements and tight junction protein expression), the ciliary motion (characterized by the ciliary beating efficiency index), and wound healing (characterized by the wound repair rate) under various stimulations (IL-4, IL-13, and dupilumab). The main outcome was a significant change in epithelial functions following exposure to IL-4, IL-13, and dupilumab for 48 h in the basal media.<br />Results: IL-4 (1, 10, and 100 ng/mL) but not IL-13 induced a significant decrease in occludin and zonula-occludens protein expression, ciliary beating efficiency, and wound repair rate in HNEC. Dupilumab (0.04 mg/mL) had no effect on HNEC and specifically restored all epithelial functions altered when cells were exposed to a 48-h IL-4 stimulation.<br />Conclusion: Dupilumab, in vitro, restored epithelial integrity by counteracting the effect of IL-4 on the epithelial barrier (increased epithelial permeability, decreased ciliary beating efficiency, and decreased wound repair rate).<br /> (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)
- Subjects :
- Humans
Middle Aged
Female
Adult
Male
Cilia drug effects
Epithelial Cells drug effects
Cells, Cultured
Chronic Disease
Wound Healing drug effects
Interleukin-4 metabolism
Nasal Mucosa drug effects
Antibodies, Monoclonal, Humanized pharmacology
Interleukin-13 metabolism
Nasal Polyps drug therapy
Rhinitis drug therapy
Rhinitis immunology
Sinusitis drug therapy
Sinusitis immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2042-6984
- Volume :
- 14
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- International forum of allergy & rhinology
- Publication Type :
- Academic Journal
- Accession number :
- 38465788
- Full Text :
- https://doi.org/10.1002/alr.23343