INHALED NO PREVENTS IL-1-INDUCED NEUTROPHIL ACCUMULATION AND ASSOCIATED ACUTE EDEMA IN ISOLATED RAT LUNGS

We determined previously that inhaled nitric oxide (NO) prevented oxid ant-dependent capillary leak in isolated rat lungs perfused with human neutrophils and fMLP via a mechanism that was independent of vasodila tation. In the present investigation we determined that inhaled NO (50 ppm) prevented oxidant-dependent acute capillary leak (as reflected b y weight gain and Ficoll retention) in isolated rat lungs given human recombinant interleukin-1 alpha (IL-1, 50 ng) intratracheally and perf used with human neutrophils. Inhaled NO also reduced neutrophil migrat ion from the vascular to the airway compartment (as reflected by lung lavage fluid neutrophil numbers and levels of myeloperoxidase), in rat s given IL-1 intratracheally and perfused with neutrophils. However, N O did not prevent IL-1-mediated increases in lung lavage levels of cyt okine-induced neutrophil chemoattractant (CINC), a potent chemokine pr oduced by alveolar macrophages and other resident cells that mediates IL-1-induced neutrophil infiltration in vivo. We conclude that inhaled NO prevented neutrophil migration and leak caused by intratracheal ad ministration of IL-1 and neutrophil perfusion in isolated rat lungs. W e speculate that NO directly inhibits neutrophil responsivity during l ung inflammation, a premise that is consistent with the known effects of NO on neutrophil function in vitro. This study provides further evi dence that inhaled NO may have important anti-inflammatory as well as vasodilator effects in acute lung injury.