Pugin J, Ricou B, Steinberg K P, Suter P M, Martin T R
Division of Medical Intensive Care, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland.
Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1850-6. doi: 10.1164/ajrccm.153.6.8665045.
Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1) have been found to be elevated in bronchoalveolar lavage (BAL) fluid and in plasma from patients with acute respiratory distress syndrome (ARDS). In order to measure the balance of proinflammatory cytokines and their inhibitors, we quantified the upregulation of intercellular adhesion molecules (ICAM-1) induced by ARDS BAL fluids in human alveolar type II-like (A459) cells, and defined proinflammatory activity as the amount of ICAM-1 induced by the SAL fluids. Proinflammatory activity was detected in 77% of the SAL fluids sampled during the first week of ARDS, was found maximal during the 3 first days after onset of ARDS, and was significantly greater than in BAL specimens from at risk patients. Blocking experiments with specific inhibitors of TNF and IL-1 added to the BAL fluids indicated that the bioactivity measured was mainly due to IL-1. In contrast, proinflammatory activity of conditioned supernates from endotoxin-treated alveolar macrophages was mostly due to TNF. Using a bioassay that measures balance of cytokines with their inhibitors, our results indicate that the net proinflammatory activity in ARDS BAL fluids is attributable to IL-1 and not to TNF.
促炎细胞因子，如肿瘤坏死因子-α（TNF）和白细胞介素-1β（IL-1），已被发现在急性呼吸窘迫综合征（ARDS）患者的支气管肺泡灌洗（BAL）液和血浆中升高。为了测量促炎细胞因子及其抑制剂的平衡，我们量化了ARDS BAL液在人II型肺泡样（A459）细胞中诱导的细胞间粘附分子（ICAM-1）的上调，并将促炎活性定义为SAL液诱导的ICAM-1的量。在ARDS第一周采集的77%的SAL液中检测到促炎活性，在ARDS发病后的前3天达到最大值，且显著高于有风险患者的BAL标本。向BAL液中添加TNF和IL-1的特异性抑制剂进行的阻断实验表明，所测量的生物活性主要归因于IL-1。相比之下，内毒素处理的肺泡巨噬细胞的条件上清液的促炎活性主要归因于TNF。使用一种测量细胞因子与其抑制剂平衡的生物测定法，我们的结果表明，ARDS BAL液中的净促炎活性归因于IL-1而非TNF。
