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哮喘与过敏的新免疫疗法及细胞因子靶点

New immunological approaches and cytokine targets in asthma and allergy.

作者信息

Stirling R G, Chung K F

机构信息

National Heart and Lung Institute, Imperial College School of Medicine, London, UK.

出版信息

Eur Respir J. 2000 Dec;16(6):1158-74. doi: 10.1034/j.1399-3003.2000.16f24.x.

Abstract

The aims of current asthma treatment are to suppress airway inflammation and control symptoms, and corticosteroids maintain a commanding position in this role. Steroids effectively suppress inflammation in the majority of patients but have little impact on the natural history of this disease. In severe asthmatics, corticosteroids may have relatively less beneficial effects. Recent advances in understanding the inflammatory and immunological mechanisms of asthma have indicated many potential therapeutic avenues that may prevent or reverse abnormalities that underlie asthma. As the roles of effector cells, and of signalling and adhesion molecules are better understood, the opportunities to inhibit or prevent the inflammatory cascade have increased. In addition, there have been advances in the synthesis of proteins, monoclonal antibodies and new small molecule chemical entities, which may provide valuable flexibility in the therapeutic approach to asthma. The novel immunological approaches include the prevention of T-cell activation, attempts to influence the balance of T-helper cell (Th) populations to inhibit or prevent Th2-derived cytokine expression, and the inhibition or blockade of the downstream actions of these cytokines such as effects on immunoglobulin-E and eosinophils. These approaches provide broad as well as highly specific targeting, and also prospects for prevention and reversal of immunological and inflammatory abnormalities associated with asthma. Hopefully, the development of effective antiasthma agents with effects beyond those provided by current therapies coupled with lesser side-effects will further address the unmet needs of asthma.

摘要

目前哮喘治疗的目标是抑制气道炎症并控制症状,而皮质类固醇在这方面占据主导地位。类固醇能有效抑制大多数患者的炎症,但对该疾病的自然病程影响甚微。在重度哮喘患者中,皮质类固醇的有益作用可能相对较小。近年来,对哮喘炎症和免疫机制的理解取得了进展,这表明了许多潜在的治疗途径,可能预防或逆转构成哮喘基础的异常情况。随着对效应细胞以及信号分子和黏附分子作用的更好理解,抑制或预防炎症级联反应的机会增加了。此外,在蛋白质、单克隆抗体和新型小分子化学实体的合成方面也取得了进展,这可能为哮喘治疗方法提供宝贵的灵活性。新颖的免疫方法包括预防T细胞活化,试图影响辅助性T细胞(Th)群体的平衡以抑制或预防Th2衍生细胞因子的表达,以及抑制或阻断这些细胞因子的下游作用,如对免疫球蛋白E和嗜酸性粒细胞的作用。这些方法提供了广泛且高度特异性的靶向作用,也为预防和逆转与哮喘相关的免疫和炎症异常带来了希望。有望开发出效果优于现有疗法且副作用较小的有效抗哮喘药物,进一步满足哮喘治疗中未被满足的需求。

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