Cargando…
Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets
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 (...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957960/ https://www.ncbi.nlm.nih.gov/pubmed/35350765 http://dx.doi.org/10.3389/fphar.2022.851940 |
_version_ | 1784676845972619264 |
---|---|
author | Pelaia, Corrado Heffler, Enrico Crimi, Claudia Maglio, Angelantonio Vatrella, Alessandro Pelaia, Girolamo Canonica, Giorgio Walter |
author_facet | Pelaia, Corrado Heffler, Enrico Crimi, Claudia Maglio, Angelantonio Vatrella, Alessandro Pelaia, Girolamo Canonica, Giorgio Walter |
author_sort | Pelaia, Corrado |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8957960 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89579602022-03-28 Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets Pelaia, Corrado Heffler, Enrico Crimi, Claudia Maglio, Angelantonio Vatrella, Alessandro Pelaia, Girolamo Canonica, Giorgio Walter Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2022-03-08 /pmc/articles/PMC8957960/ /pubmed/35350765 http://dx.doi.org/10.3389/fphar.2022.851940 Text en Copyright © 2022 Pelaia, Heffler, Crimi, Maglio, Vatrella, Pelaia and Canonica. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Pelaia, Corrado Heffler, Enrico Crimi, Claudia Maglio, Angelantonio Vatrella, Alessandro Pelaia, Girolamo Canonica, Giorgio Walter Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets |
title | Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets |
title_full | Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets |
title_fullStr | Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets |
title_full_unstemmed | Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets |
title_short | Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets |
title_sort | interleukins 4 and 13 in asthma: key pathophysiologic cytokines and druggable molecular targets |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957960/ https://www.ncbi.nlm.nih.gov/pubmed/35350765 http://dx.doi.org/10.3389/fphar.2022.851940 |
work_keys_str_mv | AT pelaiacorrado interleukins4and13inasthmakeypathophysiologiccytokinesanddruggablemoleculartargets AT hefflerenrico interleukins4and13inasthmakeypathophysiologiccytokinesanddruggablemoleculartargets AT crimiclaudia interleukins4and13inasthmakeypathophysiologiccytokinesanddruggablemoleculartargets AT maglioangelantonio interleukins4and13inasthmakeypathophysiologiccytokinesanddruggablemoleculartargets AT vatrellaalessandro interleukins4and13inasthmakeypathophysiologiccytokinesanddruggablemoleculartargets AT pelaiagirolamo interleukins4and13inasthmakeypathophysiologiccytokinesanddruggablemoleculartargets AT canonicagiorgiowalter interleukins4and13inasthmakeypathophysiologiccytokinesanddruggablemoleculartargets |