Neutrophil depletion attenuates interleukin-8 production in mild-overstretch ventilated normal rabbit lung

Objective: Acute lung injury induced by lung overstretch is associated with neutrophil influx, but the pathogenic role of neutrophils in overstretch-induced lung injury remains unclear. Design: To assess the contribution of neutrophils, we compared the effects of noninjurious large tidal volume (V-T) ventilation on lungs in normal and neutrophil-depleted animals. Setting: Research animal laboratory. Subjects: Twenty-six male Japanese white rabbits. Interventions: Animals were mechanically ventilated for 4 hrs with one of the three following protocols: large V-T (20 mL/kg), small V-T (8 mL/kg), and large V-T (20 mL/kg) with neutrophil depletion achieved by a single dose of vinblastine injection (0.75. mg/kg) intravenously 4 days before the experiment. Measurements and Main Results: Large V-T ventilation produced alveolar neutrophil influx compared with low V-T (p = .002) without evidence of edema or increased epithelial permeability. The neutrophil influx was accompanied by increases in interleukin-8 in bronchoalveolar lavage fluid (p = .04). Immunohistochemistry of large V-T lungs showed increased interleukin-8 staining in bronchial epithelial cells, alveolar epithelium, alveolar macrophages, and smooth muscles of pulmonary vessels. Neutrophil depletion attenuated the interleukin-8 increase in the lung. Large V-T did not increase plasma interieukin-8 or tumor necrosis factor-alpha in plasma and bronchoalveolar lavage fluid. No expression of p-selectin or intercellular adhesion molecule-1 was observed. Conclusions: Cyclic overstretching of normal rabbit lungs with noninjurious large V-T produced neutrophil influx and interleukin-8 increase in bronchoalveolar lavage fluid. Production of pulmonary interieukin-8 by lung overstretch might require the interaction between resident lung cells and migrated neutrophils. This study suggests that large V-T ventilation potentiates the predisposed, subclinical lung injury, such as nosocomial pneumonia or aspiration of gastric contents.