INSERM, U915, Nantes, F-44000, France.
Pharmacol Ther. 2011 Jul;131(1):114-29. doi: 10.1016/j.pharmthera.2011.03.010. Epub 2011 Apr 2.
Exacerbations of asthma are the main cause of asthma morbidity. They induce acute respiratory failure, and sometimes death. Two immunological signals acting in synergy are necessary for inducing asthma exacerbations. The first, triggered by allergens and/or unknown agents leads to the chronic Th2 inflammation characteristic of asthma. The second, caused by either viral infection, allergens, pollutants or a combination of these, results in an acute Th1 and Th2 inflammation precipitating symptoms. In both, innate and adaptive immunities are involved, providing a series of potential targets for therapy. Molecules associated to the first, chronic inflammation constitute targets for preventing therapies, when these related to the second, acute signal provide the rationale for curative treatments. Toll like receptors and bronchial epithelial cell-derived cytokines, engaged upstream of inflammation constitute interesting candidates for future treatments. The great heterogeneity of asthma has to be taken into account when considering targets for therapy to identify clusters of responders and nonresponders, and an integrative system biology approach will be necessary to go further.
哮喘恶化是哮喘发病率的主要原因。它会导致急性呼吸衰竭，有时甚至导致死亡。有两种协同作用的免疫信号对于诱导哮喘恶化是必要的。第一种信号由过敏原和/或未知因素触发，导致哮喘特征性的慢性 Th2 炎症。第二种信号由病毒感染、过敏原、污染物或这些因素的组合引起，导致急性 Th1 和 Th2 炎症，引发症状。在这两种情况下，先天和适应性免疫都参与其中，为治疗提供了一系列潜在的靶点。与第一种慢性炎症相关的分子构成了预防治疗的靶点，而与第二种急性信号相关的分子则为治愈治疗提供了依据。参与炎症上游的 Toll 样受体和支气管上皮细胞衍生细胞因子是未来治疗的有前途的候选药物。在考虑治疗靶点时，必须考虑哮喘的巨大异质性，以确定应答者和无应答者的聚类，并且需要整合系统生物学方法才能更进一步。
