Innate immunity in the pathogenesis of virus-induced asthma exacerbations.
Innate immunity in the pathogenesis of virus-induced asthma exacerbations.
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DOI：
10.1513/pats.200701-030aw
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发表时间：
2007-07-01
期刊：
影响因子：
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通讯作者：
Johnston, Sebastian L
中科院分区：
文献类型：
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作者：
Johnston, Sebastian L
哮喘的主要发病率、死亡率和卫生保健费用是急性加重的结果。然而，急性加重仅对当前治疗有部分反应，需要新的治疗方法。绝大多数哮喘急性加重与呼吸道病毒感染有关，在涉及的病毒中，约60%是人鼻病毒（RV）。RV诱导的哮喘急性发作的机制知之甚少。我们以前已经表明，成人哮喘患者对自然发生的RV感染的易感性增加。我们最近的研究探讨了先天宿主防御RV感染的机制。首先，哮喘患者的原代支气管上皮细胞在体外能复制RV到几个对数，而正常对照组的细胞对感染有抵抗力。这种抗性是正常细胞中细胞凋亡和干扰素（IFN）-β快速诱导的结果，而这些反应在哮喘细胞中缺乏。这些研究最近扩展到一个新的家族的三个相关的蛋白质，IFN-γ das 1-3，其生产也是缺乏在体外和相关的哮喘急性加重的严重程度在体内。这些研究确定了哮喘受试者对RV感染易感性增加的新机制。现在需要进一步的研究，以调查是否管理IFN-β或IFN-λ可能是有益的治疗哮喘急性发作，以确定是否类似的缺陷中观察到的儿童和非过敏性哮喘的受试者，并调查的机制，不足的IFN生产在哮喘，以帮助确定更好的治疗策略，哮喘急性发作。
The major asthma morbidity, mortality, and health care costs are a result of acute exacerbations. However, exacerbations are only partially responsive to current therapies and new approaches to treatment are needed. The great majority of acute asthma exacerbations are associated with respiratory viral infections and, of viruses implicated, approximately 60% are human rhinoviruses (RVs). The mechanisms of RV-induced asthma exacerbations are poorly understood. We have previously shown that adults with asthma have increased susceptibility to naturally occurring RV infections. Our recent studies have investigated mechanisms of innate host defense against RV infection. First, primary bronchial epithelial cells from subjects with asthma were shown to replicate RV in vitro to several logs, whereas those of normal control subjects were resistant to infection. This resistance was a result of rapid induction of apoptosis and of interferon (IFN)-beta in the normal cells, whereas these responses were deficient in asthmatic cells. These studies were recently extended to a novel family of three related proteins, the IFN-lambdas 1-3, production of which was also deficient in vitro and related to asthma exacerbation severity in vivo. These studies identify novel mechanisms for the increased susceptibility of subjects with asthma to RV infection. Further studies are now required to investigate whether administration of IFN-beta or IFN-lambda may be beneficial in the treatment of asthma exacerbations, to determine whether similar deficiencies are observed in children and in subjects with nonatopic asthma, and to investigate the mechanisms of deficient IFN production in asthma to help identify better therapeutic strategies for asthma exacerbations.