Sublethal endotoxemia promotes pulmonary cytokine-induced neutrophil chemoattractant expression and neutrophil recruitment but not overt lung injury in neonatal rats

Gram-negative sepsis and septic shock remain major causes of morbidity and mortality in the newborn. Respiratory failure is a common feature in neonat al sepsis regardless of the presence or absence of associated pneumonia. In adult animal models, cytokine-induced neutrophil chemoattractant (CINC) is a potent chemoattractant for neutrophils and believed to play a role in en dotoxin-induced lung injury. We examined this in a neonatal model. Ten-day- old Sprague-Dawley rats were injected with Salmonella enteritidis endotoxin (ETX) 0.03 mg/kg i.p. and sacrificed at baseline, 30 min, 1, 2, 4, 8 and 1 6 h post-ETX. Blood was collected by cardiac puncture. After bronchoalveola r lavage, lung tissue was collected and evaluated for neutrophil (polymorph onuclear leukocyte) recruitment by myeloperoxidase assay (MPO). Lung CINC e xpression was measured by Northern blot and ELISA. Peripheral blood leukocy tosis was noted at 1 h (p < 0.001) with counts below baseline at 2 and 4 h. Differential counts revealed neutrophilia at 8 h (p < 0.001). MPO revealed pulmonary PMN recruitment peaking at 1 h (p < 0.05) and CINC RNA and prote in expression peaked slightly later at 2 h (p < 0.001). No overt lung injur y was noted by bronchoalveolar lavage cell counts or by histology. Therefor e, pulmonary CINC expression and neutrophil recruitment follows LPS exposur e in neonatal rats. This may represent priming of the lung tissue and a sec ondary event may be necessary for injury to occur Copyright (C) 2000 S. Kar ger AG, Basel.