Department of Respiratory Medicine, National Heart and Lung Institute, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Centre for Respiratory Infection, Imperial College London, London, United Kingdom.
PLoS Pathog. 2011 Jul;7(7):e1002114. doi: 10.1371/journal.ppat.1002114. Epub 2011 Jul 14.
Rhinovirus infections are the major cause of asthma exacerbations. We hypothesised that IL-15, a cytokine implicated in innate and acquired antiviral immunity, may be deficient in asthma and important in the pathogenesis of asthma exacerbations. We investigated regulation of IL-15 induction by rhinovirus in human macrophages in vitro, IL-15 levels in bronchoalveolar lavage (BAL) fluid and IL-15 induction by rhinovirus in BAL macrophages from asthmatic and control subjects, and related these to outcomes of infection in vivo. Rhinovirus induced IL-15 in macrophages was replication-, NF-κB- and α/β interferon-dependent. BAL macrophage IL-15 induction by rhinovirus was impaired in asthmatics and inversely related to lower respiratory symptom severity during experimental rhinovirus infection. IL-15 levels in BAL fluid were also decreased in asthmatics and inversely related with airway hyperresponsiveness and with virus load during in vivo rhinovirus infection. Deficient IL-15 production in asthma may be important in the pathogenesis of asthma exacerbations.
鼻病毒感染是哮喘恶化的主要原因。我们假设白细胞介素-15（一种参与先天和获得性抗病毒免疫的细胞因子）在哮喘中可能存在缺陷，并且在哮喘恶化的发病机制中很重要。我们研究了鼻病毒在体外人巨噬细胞中诱导白细胞介素-15的情况，支气管肺泡灌洗液（BAL）中白细胞介素-15的水平以及鼻病毒在哮喘患者和对照组的 BAL 巨噬细胞中诱导白细胞介素-15的情况，并将这些与体内感染的结果相关联。鼻病毒诱导巨噬细胞产生白细胞介素-15需要复制、NF-κB 和 α/β 干扰素。哮喘患者鼻病毒诱导的 BAL 巨噬细胞白细胞介素-15的诱导作用受损，与实验性鼻病毒感染期间下呼吸道症状严重程度呈负相关。哮喘患者 BAL 液中的白细胞介素-15水平也降低，与气道高反应性和体内鼻病毒感染期间的病毒载量呈负相关。哮喘中白细胞介素-15产生的缺陷可能在哮喘恶化的发病机制中很重要。
