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Front. Pharmacol. | doi: 10.3389/fphar.2019.01387

The Intriguing Role of IL-13 in the Pathophysiology of Asthma

  • 1Department of Public Health, University of Naples Federico II, Italy
  • 2Colli Monaldi Hospital, Italy
  • 3Interdepartmental Research Center in Basic and Clinical Immunological Sciences, University of Naples Federico II, Italy
  • 4Center for Basic and Clinical Immunology Research, WAO Center of Excellence, University of Naples Federico II, Italy
  • 5Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, United Kingdom
  • 6Immunodeficiency Centre for Wales, Department of Immunology, University Hospital of Wales, United Kingdom
  • 7Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Italy
  • 8Department of Biomedical Sciences, Humanitas University, Italy
  • 9National Heart and Lung Institute, Faculty of Medicine, Imperial College London, United Kingdom


Approximately 5%–10% of asthmatic patients worldwide suffer from severe asthma. Experimental and clinical studies have demonstrated that IL-13 is an important cytokine in chronic airways inflammation. IL-13 is involved in Th2 inflammation and has been identified as a possible therapeutic target in the treatment of asthma. Two different human monoclonal antibodies (mAbs) anti-IL-13 (tralokinumab and lebrikizumab) block binding and signaling of IL-13 to its receptors, IL-13R1 and IL-13R2. Several randomized, double-blind, placebo-controlled multicenter studies have evaluated the safety and efficacy of tralokinumab and lebrikizumab in the treatment of adult patients with severe asthma, but all have failed to meet their primary end-points. No serious adverse events related to the treatment with these anti-IL-13 mAbs have been reported in these studies. These negative clinical results contrast with positive findings from blocking IL-13 signaling in experimental models of asthma, raising doubts about the transferrable value of some models. Interestingly, dupilumab, a mAb which blocks both IL-4 and IL-13 signaling reduces exacerbation rates and improves lung function in severe asthmatics. These results suggest that IL-4 and IL-13 share some, but not all functional activities in airway inflammation. Tralokinumab might show efficacy in a highly selected cohort of asthmatics characterized by overexpression of IL-13.

Keywords: Asthma, biologics, Chronic rhinosinusitis, IL-4, IL-13, Nasal polyposis, Tralokinumab

Received: 22 Jul 2019; Accepted: 31 Oct 2019.

Copyright: © 2019 Marone, Granata, Pucino, Pecoraro, Heffler, Loffredo, Scadding and Varricchi. 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.

* Correspondence:
Dr. Giancarlo Marone, Department of Public Health, University of Naples Federico II, Naples, Italy, gcmarone@hotmail.it
Dr. Gilda Varricchi, Interdepartmental Research Center in Basic and Clinical Immunological Sciences, University of Naples Federico II, Naples, Italy, gildanet@gmail.com