Protective effect of endotoxin instillation on subsequent bacteria-inducedacute lung injury in rats

The phagocytic capability afforded by neutrophil influx into the lungs is e ssential to ward off invading bacteria. The objective of this study was to evaluate the effect of prior neutrophil recruitment induced by alveolar ins tillation of endotoxin (LPS, 200 mu g/kg) 16 h before a pulmonary infection caused by instillation of live Pseudomonas aeruginosa ([PYO]: 1.5 x 10(8) colony-forming units [du]/kg) in rats. A first series of experiments showed that lipopolysaccharide(LPS) instillation induced recruitment of alveolar neutrophils that were capable, ex vivo, of elastase exocytosis, reactive ox ygen species secretion, and PYO killing. In a second set of experiments, LP S followed by PYO was compared with PYO alone (n = 11 surviving rats in eac h group). Parameters were studied 24 h after the bacterial challenge. As co mpared with PYO alone, pretreatment with LPS followed by PYO was associated with decreased mortality (0% versus 54%, p < 0.05), decreased protein leak age into bronchoalveolar lavage (BAL) fluid (1.8 +/- 0.4 versus 13.5 +/- 2. 2 mg/ml, p < 0.001), and improved bacterial clearance from BAL (4.0 +/- 4.4 x 10(2) versus 1.2 +/- 0.5 x 10(4) cfu/ml, p < 0.05) and from pulmonary pa renchyma (8.5 +/- 6.4 x 10(5) versus 1.9 +/- 0.8 x 10(7) cfu/ml, p < 0.05). We conclude that prior alveolar endotoxin instillation induces local recru itment of functionally active neutrophils, and that this is associated with resistance to subsequent experimental pneumonia.