Tillie-Leblond I, Hammad H, Desurmont S, Pugin J, Wallaert B, Tonnel A B, Gosset P
Unité de la Institute National de la Santé et de Recherche Medicale U 416, Institut Pasteur de Lille and Clinique des Maladies Respiratoires, Centre Hopitalier de Recherche Universitaire, Lille, France.
Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):586-92. doi: 10.1164/ajrccm.162.2.9907014.
In status asthmaticus (SA), severe bronchial inflammation is associated with acute respiratory failure. Neutrophils are the prominent cells found in bronchi from SA patients, but eosinophils are also recruited within the first 48 h after the beginning of mechanical ventilation (MV). Interleukin (IL)-5 and CC chemokines have been directly implicated in the pathophysiology of allergic asthma. However, their involvement in SA had not been determined. The aim of this study was to evaluate the production of CC chemokines and of IL-5 in airways from ventilated patients with SA as compared with mild asthma (A), and to assess the role of these mediators in eosinophil recruitment. We measured levels of the chemokines monocyte chemotactic proteins (MCPs)-1 and -3; regulated on activation, normal T-cell expressed and secreted (RANTES); macrophage inflammatory peptide (MIP)-1alpha; and eotaxin; and of the cytokine IL-5 in bronchial lavage fluid (BLF) from 10 SA patients, four patients without respiratory disease but undergoing ventilation (V) who were receiving MV, 11 patients with A, and eight healthy volunteers (C). We further evaluated in vitro eosinophil chemotactic activity of BLF from the various groups. Levels of MCP-1, MIP-1alpha, RANTES, and IL-5 were significantly higher in the SA than in the V, A, and C groups. MCP-3 and eotaxin values were not significantly different in the SA and other groups; however, their levels, as well as those of MIP-1alpha, RANTES, and IL-5 correlated with eosinophil influx. Eosinophil chemotactic activity in BLF was increased in asthmatic subjects (A and SA groups) as compared with the other groups, and in SA patients as compared with A patients. Addition of neutralizing anti-IL-5, anti-MCP-3, anti-eotaxin, and anti-RANTES antibodies significantly inhibited the eosinophil chemotactic activity as compared with that of native BLF. This study shows that the levels of various CC chemokines and IL-5 are increased in airways of SA patients, and are potentially involved in eosinophil recruitment.
在哮喘持续状态（SA）中，严重的支气管炎症与急性呼吸衰竭相关。中性粒细胞是SA患者支气管中发现的主要细胞，但在机械通气（MV）开始后的48小时内也会募集嗜酸性粒细胞。白细胞介素（IL）-5和CC趋化因子直接参与了过敏性哮喘的病理生理过程。然而，它们在SA中的作用尚未确定。本研究的目的是评估与轻度哮喘（A）相比，SA通气患者气道中CC趋化因子和IL-5的产生，并评估这些介质在嗜酸性粒细胞募集中的作用。我们测量了趋化因子单核细胞趋化蛋白（MCPs）-1和-3、活化调节正常T细胞表达和分泌因子（RANTES）、巨噬细胞炎性蛋白（MIP）-1α、嗜酸性粒细胞趋化因子以及细胞因子IL-5在10例SA患者、4例无呼吸系统疾病但正在接受MV的通气患者（V）、11例A患者和8名健康志愿者（C）支气管灌洗液（BLF）中的水平。我们进一步评估了各组BLF的体外嗜酸性粒细胞趋化活性。SA组中MCP-1、MIP-1α、RANTES和IL-5的水平显著高于V组、A组和C组。SA组与其他组的MCP-3和嗜酸性粒细胞趋化因子值无显著差异；然而，它们的水平以及MIP-1α、RANTES和IL-5的水平与嗜酸性粒细胞流入相关。与其他组相比，哮喘患者（A组和SA组）BLF中的嗜酸性粒细胞趋化活性增加，且SA患者比A患者更高。与天然BLF相比，添加中和抗IL-5、抗MCP-3、抗嗜酸性粒细胞趋化因子和抗RANTES抗体可显著抑制嗜酸性粒细胞趋化活性。本研究表明，SA患者气道中各种CC趋化因子和IL-5的水平升高，并可能参与嗜酸性粒细胞的募集。
