Acid-induced lung injury - Protective effect of anti-interleukin-8 pretreatment on alveolar epithelial barrier function in rabbits

Although prior experimental work has demonstrated that anti-interleukin-8 ( anti-IL-8) therapy reduces lung endothelial injury after acid instillation, there is no information regarding the effect of anti-IL-8 on the function of the alveolar epithelial barrier after acid-induced lung injury. Therefor e, the primary objective of this study was to determine the effect of acid- induced lung injury on the function of the alveolar epithelium, and secondl y to determine whether pretreatment with anti-IL-8 attenuates acid-induced injury to the lung epithelial barrier. Hydrochloric acid (pH = 1.5 in 1/3 n ormal saline) was instilled into the lungs of anesthetized, ventilated rabb its. Anti-IL-8 monoclonal antibody (2 mg/kg) or saline was given intravenou sly 5 min before acid instillation. Acid instillation into the distal airsp aces caused an increase in the alveolar epithelial permeability to protein and an approximately 50% reduction in net alveolar fluid clearance. Because a decrease in net alveolar fluid clearance could be due to lung endothelia l injury and increased fluid flux from the blood into the airspaces, additi onal experiments were carried out in which pulmonary brood flow was elimina ted. In the absence of pulmonary blood flow, acid instillation led to a 50% decrease in net alveolar fluid clearance. Pretreatment with anti-IL-8 anti body significantly reduced the acid-mediated increase in bi-directional tra nsport of protein across the alveolar epithelium and restored alveolar flui d clearance to normal. The results indicate that acid instillation causes i njury to the alveolar epithelial barrier that can be distinguished from the injury to the lung endothelium. Furthermore, pretreatment with anti-IL-8 t herapy prevents acid-induced alveolar epithelial injury, a finding of poten tial clinical importance.