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      IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma

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          Abstract

          Allergic rhinitis (AR) is a common disorder of the upper airway, while asthma is a disease affecting the lower airway and both diseases are usually comorbid. Interleukin (IL)-4 and IL-13 are critical cytokines in the induction of the pathogenic Th2 responses in AR and asthma. Targeting the IL-4/IL-13 axis at various levels of its signaling pathway has emerged as promising targeted therapy in both AR and asthma patient populations. In this review, we discuss the biological characteristics of IL-4 and IL-13, their signaling pathways, and therapeutic antibodies against each cytokine as well as their receptors. In particular, the pleiotropic roles of IL-4 and IL-13 in orchestrating Th2 responses in AR and asthma patients indicate that dual IL-4/IL-13 blockade is a promising therapeutic strategy for both diseases.

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          Most cited references103

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          T-helper type 2-driven inflammation defines major subphenotypes of asthma.

          T-helper type 2 (Th2) inflammation, mediated by IL-4, IL-5, and IL-13, is considered the central molecular mechanism underlying asthma, and Th2 cytokines are emerging therapeutic targets. However, clinical studies increasingly suggest that asthma is heterogeneous. To determine whether this clinical heterogeneity reflects heterogeneity in underlying molecular mechanisms related to Th2 inflammation. Using microarray and polymerase chain reaction analyses of airway epithelial brushings from 42 patients with mild-to-moderate asthma and 28 healthy control subjects, we classified subjects with asthma based on high or low expression of IL-13-inducible genes. We then validated this classification and investigated its clinical implications through analyses of cytokine expression in bronchial biopsies, markers of inflammation and remodeling, responsiveness to inhaled corticosteroids, and reproducibility on repeat examination. Gene expression analyses identified two evenly sized and distinct subgroups, "Th2-high" and "Th2-low" asthma (the latter indistinguishable from control subjects). These subgroups differed significantly in expression of IL-5 and IL-13 in bronchial biopsies and in airway hyperresponsiveness, serum IgE, blood and airway eosinophilia, subepithelial fibrosis, and airway mucin gene expression (all P < 0.03). The lung function improvements expected with inhaled corticosteroids were restricted to Th2-high asthma, and Th2 markers were reproducible on repeat evaluation. Asthma can be divided into at least two distinct molecular phenotypes defined by degree of Th2 inflammation. Th2 cytokines are likely to be a relevant therapeutic target in only a subset of patients with asthma. Furthermore, current models do not adequately explain non-Th2-driven asthma, which represents a significant proportion of patients and responds poorly to current therapies.
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            Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma

            Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma.
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              Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen).

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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                peerj
                PeerJ
                PeerJ Inc. (San Diego, USA )
                2167-8359
                30 May 2022
                2022
                : 10
                : e13444
                Affiliations
                [1 ]Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia , Kubang Kerian, Kelantan, Malaysia
                [2 ]Department of Otorhinolaryngology, School of Medical Sciences, Universiti Sains Malaysia , Kubang Kerian, Kelantan, Malaysia
                Article
                13444
                10.7717/peerj.13444
                9161813
                35663523
                24b9ce9f-744e-4390-8ae1-87dc5dc60089
                ©2022 Nur Husna et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 10 January 2022
                : 25 April 2022
                Funding
                Funded by: The Universiti Sains Malaysia comprising the Research University Grant
                Award ID: 1001/PPSP/8012349
                Funded by: The Research University Grant
                Award ID: 1001.PPSP.8012285
                We received funding from the Universiti Sains Malaysia comprising the Research University Grant (1001/PPSP/8012349) awarded to Kah Keng Wong and the Research University Grant (1001.PPSP.8012285) awarded to Noor Suryani Mohd Ashari. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Molecular Biology
                Allergy and Clinical Immunology
                Immunology
                Otorhinolaryngology
                Respiratory Medicine

                il-4,il-13,il-4rα,il-13rα1,allergic rhinitis,asthma,therapeutic antibodies

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