D'Agostino Bruno, Sgambato Manuela, Esposito Renata, Spaziano Giuseppe
Department of Experimental Medicine, Section of Pharmacology L. Donatelli, University of Campania "L. Vanvitelli", Naples, Italy.
Handb Exp Pharmacol. 2019;254:313-322. doi: 10.1007/164_2018_202.
Asthma is a heterogeneous chronic inflammatory disease of the airways. The most prevalent form is atopic asthma, which is initiated by the exposure to (inhaled) allergens. Intermittent attacks of breathlessness, airways hyperresponsiveness, wheezing, coughing, and resultant allergen-specific immune responses characterize the disease. Nociceptin/OFQ-NOP receptor system is able to combine anti-hyperresponsiveness and immunomodulatory actions. In particular, N/OFQ is able to inhibit airways microvascular leakage and bronchoconstriction through a presynaptic and non-opioid mechanism of action that blocks tachykinin release. Moreover, it also acts on allergenic sensitization because it is able to modulate the immune response that triggers the development of airway hyperresponsiveness through an interaction on cell membranes of dendritic cells (DCs) that are generally responsible to start and sustain allergic T helper 2 (TH2)-cell responses to inhaled allergens in asthma. In asthmatic patients, sputum showed elevated N/OFQ levels that are related to increased eosinophil counts. The addition of exogenous N/OFQ in sputum obtained from patients with severe asthma attenuated eosinophils migration and release of inflammatory mediators. These observations confirmed that elevated endogenous N/OFQ levels in asthmatic sputum were lower than the ones required to exert beneficial effects, suggesting that supplementation with exogenous N/OFQ may need. In conclusion, the innovative role of N/OFQ in counteracting airways inflammation/hyperresponsiveness opens new potential targets/strategies in asthma treatment.
哮喘是一种气道的异质性慢性炎症性疾病。最常见的形式是特应性哮喘，它由暴露于（吸入的）过敏原引发。气喘、气道高反应性、喘息、咳嗽的间歇性发作以及由此产生的过敏原特异性免疫反应是该疾病的特征。孤啡肽/孤啡肽FQ - 阿片受体系统能够结合抗高反应性和免疫调节作用。特别是，孤啡肽能够通过阻断速激肽释放的突触前和非阿片类作用机制抑制气道微血管渗漏和支气管收缩。此外，它还作用于变应性致敏，因为它能够通过与树突状细胞（DCs）细胞膜相互作用来调节免疫反应，而树突状细胞通常负责启动和维持哮喘中对吸入过敏原的变应性辅助性T细胞2（TH2）细胞反应。在哮喘患者中，痰液显示孤啡肽水平升高，这与嗜酸性粒细胞计数增加有关。向重度哮喘患者的痰液中添加外源性孤啡肽可减弱嗜酸性粒细胞迁移和炎症介质的释放。这些观察结果证实，哮喘痰液中内源性孤啡肽水平升高，但低于发挥有益作用所需的水平，这表明可能需要补充外源性孤啡肽。总之，孤啡肽在对抗气道炎症/高反应性方面的创新作用为哮喘治疗开辟了新的潜在靶点/策略。
