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

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.