Pulmonary endothelial and epithelial integrity and neutrophil infiltrationafter endotoxin in interleukin-1 receptor knockout mice

Previously we found the structural integrity of the aortic endothelium was maintained after the administration of endotoxin in type 1 interleukin-l (I L-1) receptor knockout mice. In this study, we investigated further the int egrity of pulmonary vascular endothelium, airway epithelial, pulmonary micr ovasculature, and neutrophil infiltration into the microvasculature and res piratory air spaces. Adult male C57BL/129J wild-type mice and C57BL/129J kn ockout mice possessing a homozygous deletion of the type 1 IL-1 receptor re ceived the following intraperitoneal injections; 1) Escherichia coli endoto xin (ENDT) (10 mg/kg), 2) ENDT (2 mg/kg given for 4 days), or (3) saline ve hicle. Wild-type and knockout control animals receiving saline vehicle show ed normal endothelial and epithelial ultrastructure with intact membranes. Pulmonary endothelial cell damage was found only in wild-type mice given a single 10 mg/kg endotoxin dose. Airway epithelial damage was found only in wild-type mice given a repetitive dose of endotoxin (2 mg/kg for 4 days). N eutrophil infiltration increased only in mice given a single dose of endoto xin (10 mg/kg) with the wild-type increasing by 32% and the knockouts by 6% compared with the saline control for that group respectively. Serum IL-6 a nd nitric oxide (indicators of septic shock severity and lethality) signifi cantly increased only in the mice given 10 mg/kg of endotoxin. The maintena nce of pulmonary endothelial and epithelial cell integrity and the decrease of neutrophil infiltration in the IL-l knockout mice suggest that IL-l con tributes significantly to the severity of endotoxin-induced sepsis.