Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS, a prominent role for interleukin-1

Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS, a prominent role for interleukin-1
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DOI:
10.1164/ajrccm.153.6.8665045
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发表时间:
1996-06-01
影响因子:
24.7
通讯作者:
Martin, TR
Martin, TR
中科院分区:
医学1区
文献类型:
--
作者:
Pugin, J;Ricou, B;Martin, TR

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急性呼吸窘迫综合征(ARDS)患者的支气管肺泡灌洗液和血浆中发现促炎细胞因子如肿瘤坏死因子- α (TNF)和白细胞介素-1 - β (IL-1)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液在人肺泡ii型样(A459)细胞中诱导的细胞间粘附分子-1 (ICAM-1)的上调,并将促炎活性定义为BAL液诱导的ICAM-1的量。在ARDS发病的第一周内,77%的BAL液中检测到促炎活性,在ARDS发病后的头3天内发现促炎活性最大,并且明显高于“危险”患者的BAL标本。在BAL液中加入TNF和IL-1特异性抑制剂阻断实验表明,测定的生物活性主要是由IL-1引起的。相反,内毒素处理的肺泡巨噬细胞的条件上清的促炎活性主要是由于TNF。使用生物测定法测量细胞因子与其抑制剂的平衡,我们的结果表明,ARDS BAL液体中的净促炎活性可归因于IL-1,而不是TNF。
Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF) and interleukin-1 beta (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 molecule-1 (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 BAL fluids. Proinflammatory activity was detected in 77% of the BAL 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.