Local inflammatory responses following bronchial endotoxin instillation in humans
Local inflammatory responses following bronchial endotoxin instillation in humans
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DOI：
10.1164/ajrccm.163.7.2009111
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发表时间：
2001-06-01
影响因子：
24.7
通讯作者：
Suffredini, AF
中科院分区：
文献类型：
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作者：
O'Grady, NP;Preas, HL;Suffredini, AF
为了研究局部肺部炎症，将内毒素（1-4 ng/kg）滴入34例受试者的肺段，并将生理盐水滴入对侧肺段，然后在2 h、6 h、24 h或48 h进行支气管肺泡灌洗（BAL）。内毒素滴注导致具有不同时程的局灶性炎症反应。早期阶段（2 h至6 h）显示中性粒细胞增加（p = 0.0001）细胞因子升高（肿瘤坏死因子[TNF]-α、TNF受体[TNFR]、白细胞介素[IL]-1 β、IL-1受体拮抗剂、IL-6、粒细胞集落刺激因子[G-CSF]，所有p均小于或等于0.002，但IL-10无变化）和趋化因子（IL-8、上皮中性粒细胞活化蛋白-78、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白[MIP]-1 α、MIP-1 β，所有p均小于或等于0.001，但生长调节肽-α无变化）。后期（24 h至48 h）显示中性粒细胞、巨噬细胞、单核细胞和淋巴细胞增加（所有p均小于或等于0.02），大多数介质恢复至基础水平。48 h时，BAL中炎症标志物（TNFR 1、TNFR 2、L-选择素、乳铁蛋白和髓过氧化物酶）水平持续升高（p ≤ 0.001）。在两个阶段均发生白蛋白渗透性增加（p = 0.001）。8 h时血C反应蛋白、血清淀粉样蛋白A、IL-6、IL-1 ra、G-CSF升高，但TNF-α未升高（所有p均小于或等于0.008）。与以前的静脉内毒素激发报告相比，内毒素引起的局部肺部炎症反应具有独特的炎症定性和时间特征。该模型提供了一种研究引发、放大和解决局部肺部炎症的因素的方法。
To study local lung inflammation, 34 subjects had endotoxin (1-4 ng/kg) instilled into a lung segment and saline instilled into a contralateral segment followed by bronchoalveolar lavage (BAL) at 2 h, 6 h, 24 h, or 48 h. Endotoxin instillation resulted in a focal inflammatory response with a distinct time course. An early phase (2 h to 6 h) revealed an increase in neutrophils (p = 0.0001) with elevated cytokines (tumor necrosis factor [TNF]-alpha, TNF receptors [TNFR], interleukin [IL]-1 beta, IL-1 receptor antagonist, IL-6, granulocyte-colony-stimulating factor [G-CSF], all p less than or equal to 0.002, but no change in IL-10) and chemokines (IL-8, epithelial neutrophil activating protein-78, monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1 alpha, MIP-1 beta, all p less than or equal to 0.001, but no change in growth-regulated peptide-alpha). A later phase (24 h to 48 h) showed increased neutrophils, macrophages, monocytes, and lymphocytes (all p less than or equal to 0.02), and a return to basal levels of most mediators. Elevated levels of inflammatory markers (TNFR1, TNFR2, L-selectin, lactoferrin, and myeloperoxidase) persisted in the BAL at 48 h (p less than or equal to 0.001). Increased permeability to albumin occurred throughout both phases (p = 0.001). Blood C-reactive protein, serum amyloid A, IL-6, IL-1ra, G-CSF, but not TNF-alpha increased by 8 h (all p less than or equal to 0.008). The local pulmonary inflammatory response to endotoxin has a unique qualitative and temporal profile of inflammation compared with previous reports of intravenous endotoxin challenges. This model provides a means to investigate factors that initiate, amplify, and resolve local lung inflammation.