Inhaled nitric oxide prevents interleukin-1-induced neutrophil accumulation and associated acute edema in isolated rat lungs. Guidot, David M., Brooks M. Hybertson, Roger P. Kitlowski, John E. Repine. Atlanta VA Medical Center and the Department of Medicine, Emory University and the Webb-Waring Institute for Biomedical Research and the University of Colorado Health Sciences Center, Denver, CO
APStracts 3:0054L, 1996.
We determined previously that inhaled nitric oxide (NO) prevented oxidant-dependent capillary leak in isolated rat lungs perfused with human neutrophils and FMLP via a mechanism that was independent of vasodilatation. In the present investigation we determined that inhaled nitric oxide (50 ppm) prevented oxidant-dependent acute capillary leak (as reflected by weight gain and Ficoll retention) in isolated rat lungs given human recombinant interleukin-1[alpha] (IL -1, 50 ng) intratracheally and perfused with human neutrophils. Inhaled NO also reduced neutrophil migration from the vascular to the airway compartment (as reflected by lung lavage fluid neutrophil numbers and levels of myeloperoxidase), in rats given IL-1 intratracheally and perfused with neutrophils. However, NO did not prevent IL-1-mediated increases in lung lavage levels of cytokine -induced neutrophil chemoattractant (CINC), a potent chemokine produced 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 administration of IL-1 and neutrophil perfusion in isolated rat lungs. We speculate that NO directly inhibits neutrophil responsivity during lung inflammation - a premise that is consistent with the known effects of NO on neutrophil function in vitro. This study provides further evidence that inhaled NO may have important anti-inflammatory as well as vasodilator effects in acute lung injury. 

Received 17 January 1996; accepted in final form 26 March 1996.
APS Manuscript Number L20-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 16 April 96