TUMOR-NECROSIS-FACTOR INDUCED ACUTE LUNG LEAK IN RATS - LESS-THAN WITH INTERLEUKIN-1

Although local tumor necrosis factor-alpha (TNF) release by alveolar m acrophages has been postulated to contribute to the development of acu te respiratory distress syndrome (ARDS), the effects of instilling TNF intratracheally on the development of acute lung leak are not known. Our goal was to determine the effect of intratracheally administered T NF on the development of acute lung leak in rats. We found that rats g iven TNF (500 ng) 5 hours previously intratracheally had increased (p < 0.05) lung ravage cytokine induced neutrophil chemoattractant (CINC) concentrations, lung lavage neutrophils, lung myeloperoxidase (MPO) a ctivity, and lung leak compared to saline-treated control rats. Howeve r, all of the responses following TNF instillation were much lower tha n the responses to interleukin-1 alpha (IL-1) instillation. For exampl e, instilling 50 ng of IL-1 caused 6.4 times the increases in lung lav age CINC concentrations, 15.5 times the increase in lung lavage neutro phils, 3.6 times the increase in lung MPO activity and 3.8 times the i ncrease in lung leak caused by giving 500 ng of TNF intratracheally. C otreatment with TNF-binding protein decreased both lung MPO and lung l eak increases in rats given TNF intratracheally. These observations su ggest that locally elevated levels of TNF may induce lung neutrophil r ecruitment and acute lung leak but that IL-1 is a much more potent age nt than TNF in causing lung neutrophil accumulation and lung leak.