Interleukin-18 expression, CD8+ T cells, and eosinophils in lungs of nonsmokers with fatal asthma
Interleukin-18 expression, CD8+ T cells, and eosinophils in lungs of nonsmokers with fatal asthma
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DOI：
10.1016/j.anai.2013.09.004
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发表时间：
2014-01-01
影响因子：
5.9
通讯作者：
Hoshino, Tomoaki
中科院分区：
文献类型：
--
作者：
Oda, Hanako;Kawayama, Tomotaka;Hoshino, Tomoaki
背景资料：死于哮喘的非吸烟者肺部气道炎症的过程目的：对因哮喘死亡的非吸烟者进行检测，以排除慢性阻塞性肺疾病（COPD），并与控制良好的轻度哮喘和非吸烟者比较，探讨肺组织中炎性细胞和白细胞介素-18（IL-18）及其受体的表达。肺组织在尸检时从12名患有致命性哮喘的非吸烟者（排除慢性阻塞性肺疾病的病例）、5名控制良好的轻度哮喘的非吸烟者和10名因肺癌接受手术切除的非吸烟者中获得。结果：与其他两组相比，哮喘组肺组织中嗜酸性粒细胞和淋巴细胞数量明显增多，嗜碱性粒细胞和巨噬细胞数量无明显变化。肺中性粒细胞计数在致命性哮喘组和轻度哮喘组之间没有显著差异，但在致命性哮喘组中显著高于非吸烟者。致死性哮喘组肺组织中CD 8 + T细胞较其他两组明显增加，而CD 4 + T细胞无明显变化。结论：Caspase-1抑制剂、抗IL-18抗体、抗IL-18受体抗体、IL-18结合蛋白或IL-18信号转导通路下游基因的抑制剂可能对重症哮喘患者的治疗有临床意义。(C)2014年美国过敏，哮喘和免疫学学院。爱思唯尔公司出版All rights reserved.
Background: The process of airway inflammation in the lungs of nonsmokers who die of asthma (fatal asthma) has not been reported in detail.Objective: To examine nonsmokers who had died of asthma to exclude chronic obstructive pulmonary disease and investigate pulmonary inflammatory cells and the expression of interleukin-18 (IL-18) and its receptor in lung tissues compared with those in patients with well-controlled mild asthma and nonsmokers.Methods: Lung tissues were obtained at autopsy examination from 12 nonsmokers with fatal asthma, excluding cases of chronic obstructive pulmonary disease, and from 5 nonsmokers with well-controlled mild asthma and 10 nonsmokers who had undergone surgical resection for lung cancer. Pulmonary inflammatory cells were examined and the expression of the proinflammatory cytokine IL-18 and its receptor in the lungs was evaluated.Results: The numbers of eosinophils and lymphocytes, but not basophils or macrophages, were significantly increased in the lungs of patients with fatal asthma compared with the other 2 groups. The lung neutrophil count did not differ significantly between the fatal and mild asthma groups but was significantly higher in the fatal asthma group than in nonsmokers. CD8(+) T cells, but not CD4(+) T cells, were significantly increased in the lungs of the fatal asthma group compared with the other 2 groups. IL-18 protein and IL-18 receptor were strongly expressed in the lungs in the fatal asthma group.Conclusion: Caspase-1 inhibitors, anti-IL-18 antibodies, anti-IL-18 receptor antibodies, IL-18 binding protein, or inhibitors of genes downstream of the IL-18 signal transduction pathway may be of clinical benefit for the treatment of patients with severe asthma. (C) 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.