Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets.
IL-13
IL-4
IL-4 receptor
dupilumab
severe asthma
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2022
2022
Historique:
received:
11
01
2022
accepted:
21
02
2022
entrez:
30
3
2022
pubmed:
31
3
2022
medline:
31
3
2022
Statut:
epublish
Résumé
Interleukins (IL)-4 and -13 play a pivotal role in the pathobiology of type-2 asthma. Indeed, IL-4 is crucially involved in Th2 cell differentiation, immunoglobulin (Ig) class switching and eosinophil trafficking. IL-13 cooperates with IL-4 in promoting IgE synthesis, and also induces nitric oxide (NO) production, goblet cell metaplasia and fibroblast proliferation, as well as elicits contractile responses and hyperplasia of airway smooth muscle cells. IL-4 and IL-13 share common signaling pathways, activated by the binding of both cytokines to receptor complexes including the α-subunit of the IL-4 receptor (IL-4Rα). Therefore, the subsequent receptor dimerization is responsible for the pathophysiologic effects of IL-4 and IL-13. By selectively blocking IL-4Rα, the fully human IgG4 monoclonal antibody dupilumab behaves as a dual receptor antagonist of both IL-4 and IL-13. Through this mechanism of action, dupilumab exerts effective therapeutic actions in type-2 inflammation, thus decreasing asthma exacerbations, FeNO (fractional exhaled NO) levels, and the intake of oral corticosteroids (OCS). In addition to being approved for the add-on biological therapy of severe asthma, dupilumab has also been licensed for the treatment of nasal polyposis and atopic dermatitis.
Identifiants
pubmed: 35350765
doi: 10.3389/fphar.2022.851940
pii: 851940
pmc: PMC8957960
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
851940Informations de copyright
Copyright © 2022 Pelaia, Heffler, Crimi, Maglio, Vatrella, Pelaia and Canonica.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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