Blockade of neutrophil responses in aspiration pneumonia via ELR-CXC chemokine antagonism does not predispose to airway bacterial outgrowth

Pneumonia associated with aspiration of bacterial-laden gastric contents is characterized by Glu-Leu-Arg (ELR)-CXC chemokine (e.g., CXC2L1, CXCL8) expression leading to local neutrophil sequestration. This neutrophil response is designed to be protective, but overly aggressive responses can be pathogenic in themselves. Herein we assessed whether blocking neutrophil responses in a guinea pig model of aspiration pneumonia would foster airway bacterial growth. Guinea pigs (n = 5) were challenged intranasally with saline, acidified saline or acidified gastric contents (35 mg/kg body weight, pH 2.0) and treated subcutaneously with 250 μg/kg of the human ELR-CXC chemokine antagonist CXCL8(3–72)K11R/G31P (G31P) or saline. After 20 h the animals' airway inflammatory responses and bacterial burdens were assessed. A loss of vascular integrity was apparent in the lungs of the saline-treated aspiration pneumonia animals (12.07+/−1.3% of the pleural surfaces exhibited hemorrhagic consolidation, 4.6 × 106 RBC/ml bronchoalveolar lavage fluid [BALF]), as was a pulmonary neutrophilia. The BAL fluids contained gram-negative and -positive bacteria (total load, 6.3+/−3.2 × 107 CFU/ml BALF) that are associated with nosocomial infections in humans. The G31P-treatments attenuated the pulmonary vascular complications (2.27+/−0.5% pleural surface hemorrhagic consolidation, 0.46 × 106 RBC/ml BALF), and reduced the pulmonary neutrophilia by ≥86%. The G31P-treatments did not lead to significant changes in the airway bacterial loads (total load, 3.46+/−1.8 × 107 CFU/ml BALF). This data indicates that attenuation of the pulmonary neutrophil response in aspiration pneumonia reduces pathology very significantly but does not reduce the efficiency of pulmonary bacterial clearance.