Am. J. Respir. Crit. Care Med., Volume 160, Number 5, November 1999, 1443-1449

Interleukin-8 Mediates Injury from Smoke Inhalation to both the Lung Endothelial and the Alveolar Epithelial Barriers in Rabbits

MARC LAFFON, JEAN-FRANÇOIS PITTET, KATHARINA MODELSKA, MICHAEL A. MATTHAY, and DAVID M. YOUNG

Department of Anesthesia, Laboratory of Surgical Research, San Francisco General Hospital; Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, California

Although prior studies have shown that smoke inhalation causes lung endothelial injury and formation of pulmonary edema, there is no information about the effect of smoke inhalation on the function of the alveolar epithelial barrier. Therefore, the primary objective of this study was to determine the effect of smoke-induced lung injury on the alveolar epithelial barrier in a rabbit experimental model. The second objective was to investigate whether pretreatment with a monoclonal anti-interleukin (IL)-8 antibody prevented alveolar epithelial barrier injury after smoke inhalation. Anesthetized rabbits were tracheotomized and were insufflated with cooled smoke generated from burning cotton cloth (75 breaths). In some experiments, anti-IL-8 antibody or an irrelevant antibody (2 mg/ kg) was given intravenously 5 min before insufflation of cotton smoke. Smoke inhalation caused a significant increase in the alveolar epithelial permeability to protein and a 40% reduction in the fluid transport capacity of the alveolar epithelium. Pretreatment with anti-IL-8 antibody, but not with an irrelevant-isotype antibody, significantly reduced the smoke-mediated increase in bidirectional transport of protein across the alveolar epithelium, and restored alveolar liquid clearance to a normal level. The results of the study show that smoke inhalation causes injury to both the alveolar epithelial barrier and the lung endothelium, and that IL-8 is an important mediator of this injury. Laffon M, Pittet J-F, Modelska K, Matthay MA, Young DM. Interleukin-8 mediates injury from smoke inhalation to both the lung endothelial and the alveolar epithelial barriers in rabbits.

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