Enhanced expression of interleukin-18 and its receptor in idiopathic pulmonary fibrosis
Enhanced expression of interleukin-18 and its receptor in idiopathic pulmonary fibrosis
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DOI：
10.1165/rcmb.2003-0306oc
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发表时间：
2004-12-01
影响因子：
6.4
通讯作者：
Aizawa, H
中科院分区：
文献类型：
--
作者：
Kitasato, Y;Hoshino, T;Aizawa, H
特发性肺纤维化(IPF)/通常间质性肺炎（UIP）是一种主要的间质性肺疾病（ILD）。最近，我们建立了一种新的ILD小鼠模型，在该模型中，每日给予白细胞介素(IL)-18和IL-2可诱导致死性肺损伤，提示IL-18参与ILD的发病机制。本研究利用免疫组织化学方法，利用抗IL-18单克隆抗体和抗IL-18R α单克隆抗体（H44），分析了18例IPF/UIP患者和13例对照组肺组织中IL-18和IL-18受体(IL-18R) α的表达。IL-18在对照组的支气管肺泡上皮、肺泡巨噬细胞和小血管内皮中表达，在IPF患者的大多数肺细胞中大量表达。IL-18Ralpha在对照组的支气管肺泡上皮和肺泡巨噬细胞中表达，在IPF患者的间质细胞中强烈表达，尤其是在成纤维细胞灶（FF）中。有趣的是，IL-18Ralpha的表达仅在已建立纤维化的区域中观察到微弱。半定量分析显示FF组织学评分与FF病变组织中IL-18Ralpha表达水平显著相关。IPF患者血清和支气管肺泡灌洗液中IL-18水平明显高于对照组。我们的研究结果提示IL-18和IL-18R参与了IPF/UIP的发病机制。
Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is a major interstitial lung disease (ILD). Recently, we established a new mouse model for ILD in which daily administration of interleukin (IL)-18 with IL-2 induces lethal lung injury, suggesting that IL-18 is involved in the pathogenesis of ILD. Here, utilizing immunohistochemistry, we have analyzed IL-18 and IL-18 receptor (IL-18R) alpha expression in the lungs of 18 patients with IPF/UIP and 13 control subjects by using monoclonal anti-IL-18 antibodies and a new monoclonal antibody for IL-18Ralpha (H44). IL-18 was expressed in bronchoalveolar epithelium, alveolar macrophages, and the endothelium of small vessels in control subjects, and was abundantly expressed in the majority of pulmonary cells in patients with IPF. IL-18Ralpha was expressed in bronchoalveolar epithelium and alveolar macrophages in control subjects, and was strongly expressed in interstitial cells in patients with IPF, especially in the fibroblastic foci (FF). Interestingly, IL-18Ralpha, expression was only weakly observed in areas showing established fibrosis. Semiquantitative analysis revealed that the histologic FF score was significantly correlated with the IL-18Ralpha expression level in FF lesions. Moreover, IL-18 levels in the serum and bronchoalveolar lavage fluid of patients with IPF were significantly higher than those in control subjects. Our findings suggest IL-18 and IL-18R are involved in the pathogenesis of IPF/UIP.