Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets.
Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets.
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DOI：
10.3389/fphar.2022.851940
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发表时间：
2022
影响因子：
5.6
通讯作者：
Canonica GW
中科院分区：
文献类型：
--
作者：
Pelaia C;Heffler E;Crimi C;Maglio A;Vatrella A;Pelaia G;Canonica GW
白介素4和白介素13在2型哮喘的发病机制中起着重要作用。事实上，IL-4在Th2细胞分化、免疫球蛋白(Ig)类转换和嗜酸性粒细胞运输中起着至关重要的作用。IL-13与IL-4协同促进IgE合成，并可诱导一氧化氮(NO)生成、杯状细胞化生和成纤维细胞增殖，以及引起气道平滑肌细胞收缩反应和增殖。IL-4和IL-13具有共同的信号转导途径，由两种细胞因子与包括IL-4受体α亚单位(IL-4Rα)在内的受体复合体结合而激活。因此，随后的受体二聚体参与了IL-4和IL-13的病理生理效应。通过选择性地阻断IL-4Rα，完全人类免疫球蛋白4的单抗DUPILUMA表现为IL-4和IL-13的双重受体拮抗剂。通过这一作用机制，dupilumab对2型炎症发挥了有效的治疗作用，从而减少了哮喘加重、FeNO(呼出一氧化氮的部分)水平和口服皮质类固醇(OCS)的摄入量。除了被批准用于严重哮喘的生物治疗外，dupilumab还被批准用于治疗鼻息肉病和特应性皮炎。
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.
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DOI：
10.1183/09031936.00068712
发表时间：
2014-03
期刊：
The European respiratory journal
影响因子：
--
作者：
Firszt R;Francisco D;Church TD;Thomas JM;Ingram JL;Kraft M
通讯作者：
Kraft M
影响因子：
4.3
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影响因子：
13.3
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DOI：
10.1016/j.jaci.2014.11.037
发表时间：
2015-07
期刊：
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影响因子：
--
作者：
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DOI：
10.5414/alx02194e
发表时间：
2021
期刊：
Allergologie select
影响因子：
--
作者：
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通讯作者：
Albrecht M