Cytokine Pathways in Allergic Disease
Cytokine Pathways in Allergic Disease
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DOI：
10.1177/0192623311430694
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发表时间：
2012-02-01
影响因子：
1.5
通讯作者：
Ma, Hak-Ling
中科院分区：
文献类型：
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作者：
Williams, Cara M. M.;Rahman, Saifur;Ma, Hak-Ling
细胞因子在过敏性细胞间通讯网络中至关重要，并且它们通过促炎性白细胞的募集和活化以及在慢性疾病中促纤维化/重塑事件而促成疾病病理学。Th 2细胞因子主要在轻度至中度过敏性哮喘中占主导地位，尽管使用IL-4和IL-5抑制剂的临床试验尚未提供在过敏动物模型中观察到的稳健疗效。这些结果不仅突出了过敏性疾病的复杂性，而且还指出了其他细胞因子网络在驱动病理学中的重要性。Th 2/Th 1/Th 17细胞因子平衡可受起始过敏性触发物影响的事实强调了该疾病的异质性。例如，屋尘螨变应原Der p 2通过将脂多糖呈递给Toll样受体-4以激活包括先天型细胞因子的炎性基因来模拟MD-2的活性。在这里，我们讨论了新的细胞因子球员，胸腺基质淋巴细胞（TSLP），IL-33，IL-25和IL-9的功能，并描绘非多余的作用，IL-4和IL-13在过敏性疾病。在这些和其他细胞因子网络的特性的持续努力将是必不可少的理解复杂的致病机制，支持过敏性疾病和指导有针对性的治疗干预。
Cytokines are critical in allergic intercellular communication networks, and they contribute to disease pathology through the recruitment and activation of pro-inflammatory leukocytes and in chronic disease to pro-fibrotic/remodeling events. Th2 cytokines predominate primarily in mild to moderate allergic asthma, although clinical trials with inhibitors of IL-4 and IL-5 have not provided the robust efficacy observed in animal models of allergy. These results not only highlight the complexity of allergic disease, but they also point to the importance of other cytokine networks in driving pathology. The heterogeneous nature of the disease is emphasized by the fact that the Th2/Th1/Th17 cytokine balance can be influenced by the initiating allergic trigger. For example, the house dust mite allergen Der p 2 mimics the activity of MD-2 by presenting lipopolysaccharide to Toll-like receptor-4 for the activation of inflammatory genes including innate-type cytokines. Here we discuss the functions of the novel cytokine players, thymic stromal lymphopoetin (TSLP), IL-33, IL-25, and IL-9 and delineate nonredundant roles for IL-4 and IL-13 in allergic disease. Persistent efforts in the characterization of these and other cytokine networks will be essential for understanding the complex pathogenic mechanisms that underpin allergic disease and for guiding targeted therapeutic interventions.