Recent studies in mice with cystic fibrosis (CF)-like lung disease identified interleukin (IL)-1 receptor (IL-1R) signalling as an important pathway triggering neutrophilic airway inflammation that constitutes a key risk factor in the onset and progression of lung disease in patients with CF [1–4]. These studies demonstrated that CF-like airway mucus obstruction causes epithelial hypoxia and necrosis, which in turn leads to the release of IL-1α from dying cells and activation of IL-1R signalling triggering neutrophilic inflammation and structural lung damage in vivo [1, 5]. Further, necrotic epithelial cells were detected in mucus-obstructed airways in lung sections from patients with CF [1]. Hypoxic cell death is a well-established trigger of sterile neutrophilic inflammation in many other organs and previous studies have identified IL-1R signalling as a key pathway required for triggering this inflammatory response to dying cells [6]. In addition, the gene encoding the IL-1R ligand IL-1β that is induced by bacterial infection has been identified as a genetic modifier of CF by independent North American and European CF modifier studies [7, 8]. Collectively, these studies suggest that IL-1R signalling may play an important role in the pathogenesis of neutrophilic inflammation that is invariably detected in the airways of patients with CF, in the absence and presence of bacterial infection [2, 3]. However, the role of IL-1R and its association with disease severity in patients with CF remains unknown. IL1R modifies disease severity in CF patients, emphasizing the significance of IL-1 signalling for CF pathogenesis http://ow.ly/pIN730gL10G

中文翻译：

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信息丰富的基因内微卫星标记表明 IL-1 受体作为囊性纤维化的遗传修饰剂

最近对患有囊性纤维化 (CF) 样肺病小鼠的研究发现，白细胞介素 (IL)-1 受体 (IL-1R) 信号是触发中性粒细胞气道炎症的重要途径，是肺病发生和进展的关键危险因素CF 患者 [1-4]。这些研究表明，CF 样气道粘液阻塞会导致上皮缺氧和坏死，进而导致死亡细胞释放 IL-1α 并激活 IL-1R 信号传导，从而引发体内中性粒细胞炎症和结构性肺损伤 [1, 5] ]。此外，在 CF 患者肺切片的粘液阻塞气道中检测到坏死的上皮细胞 [1]。缺氧细胞死亡是许多其他器官中无菌中性粒细胞炎症的公认触发因素，之前的研究已经确定 IL-1R 信号传导是触发对死亡细胞的这种炎症反应所需的关键途径 [6]。此外，由细菌感染诱导的编码 IL-1R 配体 IL-1β 的基因已被独立的北美和欧洲 CF 修饰物研究确定为 CF 的遗传修饰物 [7, 8]。总的来说，这些研究表明 IL-1R 信号传导可能在中性粒细胞炎症的发病机制中发挥重要作用，在不存在和存在细菌感染的情况下，CF 患者的气道中总会检测到这种炎症 [2, 3]。然而，IL-1R 的作用及其与 CF 患者疾病严重程度的相关性仍然未知。