Interleukin-8 mediates injury from smoke inhalation to both the lung endothelial and the alveolar epithelial barriers in rabbits

Although prior studies have shown that smoke inhalation causes lung endothe lial 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 th e effect of smoke-induced lung injury on the alveolar epithelial barrier in a rabbit experimental model. The second objective was to investigate wheth er pretreatment with a monoclonal anti-interleukin (IL)-8 antibody prevente d alveolar epithelial barrier injury after smoke inhalation. Anesthetized r abbits were tracheotomized and were insufflated with cooled smoke generated from burning cotton cloth (75 breaths). In some experiments, anti-IL-8 ant ibody or an irrelevant antibody (2 mg/ kg) was given intravenously 5 min be fore insufflation of cotton smoke. Smoke inhalation caused a significant in crease in the alveolar epithelial permeability to protein and a 40% reducti on in the fluid transport capacity of the alveolar epithelium. Pretreatment with anti-ll-g antibody, but not with an irrelevant-isotype antibody, sign ificantly reduced the smoke-mediated increase in bidirectional transport of protein across the alveolar epithelium, and restored alveolar liquid clear ance to a normal level. The results of the study show that smoke inhalation causes injury to both the alveolar epithelial barrier and the lung endothe lium, and that IL-g is an important mediator of this injury.