Expression of inflammatory cytokines and Fas in alveolar macrophages from ARDS patients

本研究旨在探讨肺泡巨噬细胞(AM)中诱导型一氧化氮合酶(INOS)、促炎性细胞因子及细胞凋亡相关因子在脓毒症后急性呼吸窘迫综合征(ARDS)发病机制中的作用。为探讨脓毒症后急性呼吸窘迫综合征(ARDS)患者肺泡巨噬细胞(AM)中iNOS和IL-1、IL-6、IL-8的表达。同时检测支气管肺泡灌洗液(BALF)上清液和血清中NOx、IL-1、IL-6、IL-8水平。为了排除长期机械通气、单纯脓毒症综合征和/或镇静药物的影响，将脓毒症后ARDS患者的所有数据与正常对照组和机械通气一周但未达到ARDS标准的脓毒症患者(LTV组)进行比较。应用免疫荧光技术，我们的研究证实，在脓毒症后ARDS的早期阶段，人肺泡巨噬细胞中有iNOS的强烈表达。对照组AM未见iNOS表达，LTV组AM未见iNOS表达。本研究的另一个发现是ARDS患者BALF上清液和血清中IL-6和IL-8水平明显高于对照组和LTV组。与对照组相比，ARDS组BALF上清液中NOx、IL-6和IL-8水平显著升高。提示肺泡巨噬细胞诱导型一氧化氮合酶及其产生的促炎细胞因子在急性肺损伤的发病机制中可能起重要作用，可作为监测脓毒症后ARDS患者肺功能紊乱的指标。

The objective of this study was to evaluate the role of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines together with apoptosis related factors in alveolar macrophages (AMs) in the pathogenesis of acute respiratory distress syndrome (ARDS) following sepsis. To investigate these expressions in AMs collected from ARDS patients following sepsis, the expression of iNOS and IL-1□,IL-6,IL-8 in AMs were determined by the immunofluorescent technique. The level of NOx, IL-1□,IL-6,and IL-8 in bronchoalveolar lavage fluid (BALF) supernatant and in serum were measured concurrently. To exclude the effect of the long-term ventilation, sepsis syndrome alone, and/or the administration of sedative drugs, all data obtained from patients with ARDS following sepsis were compared with the data from normal control subjects and from septic patients who had been mechanically ventilated for one week without fulfilling the criteria of ARDS (LTV group). Using immunofluorescent technique, our study identified the strong expression of iNOS in AMs of human lungs predominantly at the early stage of ARDS following sepsis. Whereas no expression of iNOS was observed in AMs from the control group, nor was observed in AMs from the LTV group. Another finding of this study is the marked increase of IL-6 and IL-8 levels in BALF supernatant and the serum from patients with ARDS as compared with the control and the LTV group. Also, statistically significant elevations were detected in NOx, IL-6 and IL-8 levels in BALF supernatant from the ARDS group compared with the control group. The result suggests that iNOS together with proinflammatory cytokines produced by AMs might play a pivotal role in the pathogenesis of acute lung injury and be useful for monitoring disorders in the lung of patients with ARDS following sepsis.