The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation.
The Therapeutic Potential of Targeting Cytokine Alarmins to Treat Allergic Airway Inflammation.
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DOI：
10.3389/fphys.2016.00214
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发表时间：
2016
影响因子：
4
通讯作者：
Siracusa MC
中科院分区：
文献类型：
--
作者：
Sy CB;Siracusa MC
哮喘是一种异质性疾病，其导致呼吸困难、咳嗽和喘息的反复发作，影响全世界数百万人。虽然哮喘的确切原因尚不清楚，但研究表明，遗传易感性和环境暴露于各种过敏原和病原体的组合有助于其发展。目前，控制哮喘的最常见治疗是β2-肾上腺素能受体激动剂和皮质类固醇的双重组合。然而，研究表明，一些患者对这些药物反应不佳，而另一些患者则会出现明显的副作用。据报道，大多数哮喘与辅助性T细胞2型（TH 2）反应有关。在这些患者中，过敏原激发引发气道中TH 2细胞的流入，导致TH 2相关细胞因子的产生增加并促进过敏诱导的哮喘。因此，靶向这一通路的生物制剂可能为治疗与哮喘相关的过敏性气道炎症提供一种替代方法。到目前为止，只有两种分别针对免疫球蛋白E和白细胞介素-5的生物制剂（奥马珠单抗和美泊利珠单抗）获得FDA批准，并被开给哮喘患者。然而，最近的研究报告说，针对TH 2反应的其他成分也显示出很大的希望。本文就过敏性哮喘的免疫学机制作一综述。此外，我们将讨论目前用于治疗哮喘的治疗策略，包括其局限性。最后，我们将强调使用生物制剂治疗哮喘相关的过敏性气道炎症的好处，重点是靶向细胞因子alarmins，特别是胸腺基质淋巴细胞生成素的潜力。
Asthma is a heterogeneous disorder that results in recurrent attacks of breathlessness, coughing, and wheezing that affects millions of people worldwide. Although the precise causes of asthma are unclear, studies suggest that a combination of genetic predisposition and environmental exposure to various allergens and pathogens contribute to its development. Currently, the most common treatment to control asthma is a dual combination of β2-adrenergic receptor agonists and corticosteroids. However, studies have shown that some patients do not respond well to these medications, while others experience significant side effects. It is reported that the majority of asthmas are associated with T helper type 2 (TH2) responses. In these patients, allergen challenge initiates the influx of TH2 cells in the airways leading to an increased production of TH2-associated cytokines and the promotion of allergy-induced asthma. Therefore, biologics that target this pathway may provide an alternative method to treat the allergic airway inflammation associated with asthma. As of now, only two biologics (omalizumab and mepolizumab), which target immunoglobulin E and interleukin-5, respectively, are FDA-approved and being prescribed to asthmatics. However, recent studies have reported that targeting other components of the TH2 response also show great promise. In this review, we will briefly describe the immunologic mechanisms underlying allergic asthma. Furthermore, we will discuss the current therapeutic strategies used to treat asthma including their limitations. Finally, we will highlight the benefits of using biologics to treat asthma-associated allergic airway inflammation with an emphasis on the potential of targeting cytokine alarmins, especially thymic stromal lymphopoietin.