Study for roles of inflammatory cells and cytokines in asthma death, COPD and mouse pulmonary disease models

背景：嗜酸性粒细胞、CD4+T细胞和Th2细胞因子被认为与哮喘的发生有关。最近有文章报道促炎IL-18基因多态性与支气管哮喘病情严重程度显著相关。然而，非吸烟者哮喘死亡的肺部气道炎症过程的细节尚未报道。方法：我们在尸检中获得了12例死于哮喘的非吸烟者的肺组织。他们死于1973年至1998年。5名控制良好的轻度哮喘患者和10名接受肺癌切除手术的非吸烟者也获得了肺组织。我们检测了肺炎症细胞，并评估了IL-18及其受体在肺中的表达。结果：与轻度哮喘患者和非吸烟者相比，肺嗜酸性粒细胞和淋巴细胞数量明显增加，而嗜碱性粒细胞和巨噬细胞数量明显增加。有趣的是，当比较致命性和轻度哮喘时，中性粒细胞没有显着差异，但哮喘死亡患者的肺部中性粒细胞比非吸烟者明显增加。与轻度哮喘患者和不吸烟者相比，致命性哮喘患者肺部的CD8+T细胞显著增加，而CD4+T细胞没有显著增加。IL-18蛋白在哮喘死亡的支气管肺泡上皮细胞和肺部炎症细胞中强烈表达。il - 18r α蛋白在哮喘死亡患者肺部炎症细胞，尤其是CD8+T细胞中表达增强。结论：肺内CD8+T细胞、嗜酸性粒细胞及IL-18蛋白过表达可能在哮喘死亡的发病机制中起重要作用。

Background : Eosinophils, CD4+T cells, and Th2 cytokines are thought to contribute to the development of asthma. Recently, a paper reported that pro-inflammatory IL-18 gene polymorphism was significantly associated with the disease severity of bronchial asthma. However, the detail of airway inflammation process in the lungs of nonsmoker asthma death has not reported.Method : We obtained lung tissues from 12 nonsmokers who died of asthma at autopsy. They died from 1973 to 1998.Lung tissues were also obtained from 5 well-controlled mild asthma patients and 10 nonsmokers who underwent lung cancer extirpation. We examined pulmonary inflammatory cells, and also evaluated the expression of IL-18 and its receptor in the lungs.Result : The numbers of eosinophils and lymphocytes, but not basophils, nor macrophages were significantly and greatly increased in the lungs when compared with mild asthmatics and nonsmokers. Interestingly, neutrophils were not significantly different when comparing fatal and mild asthmas, but were significantly increased in the lungs of asthma deaths than seen in nonsmokers. CD8+T cells but not CD4+T cells were significantly and greatly increased in the lungs of fatal asthma patients when compared to mild asthmas and nonsmokers. IL-18 proteins were strongly expressed in the bronchoalveolar epithelial cells and pulmonary inflammatory cells in asthma deaths. Moreover, IL-18Rαproteins were enhanced in the pulmonary inflammatory cells, especially CD8+T cells in the lungs of asthma death.Conclusion : CD8+T cells, eosinophils and over-expressed IL-18 proteins in the lungs may play an important role in the pathogenesis of asthma death.