RECOMBINANT ENDOTOXIN NEUTRALIZING PROTEIN IMPROVES SURVIVAL FROM ESCHERICHIA-COLI SEPSIS IN RATS

Objective: A recombinant endotoxin neutralizing protein was evaluated for its ability to ameliorate the effects of Escherichia coli sepsis in rats. Design: Prospective, controlled animal trial. Setting: Hospital animal research laboratory. Subjects: Wistar rats, treated with gentamicin 1 hr after challenge with intraperitoneal E. coli O18ac. Interventions: The animals received a recombinant endotoxin neutralizing protein, in doses of 5, 25, or 50 mg/kg, either 30 or 60 mins after challenge; controls received saline. Measurements and Main Results: Geometric mean serum endotoxin concentrations in endotoxin neutralizing protein-treated animals did not differ from control animals. Tumor necrosis factor concentrations in animals treated with endotoxin neutralizing protein 30 mins after challenge were significantly lower than controls. Animals treated with 25 or 50 mg/kg of endotoxin neutralizing protein 30 mins after E. cell challenge had significant improvements in survival compared with controls. Animals treated with 50 mg/kg of endotoxin neutralizing protein 60 mins after E. coli challenge had significant improvements in survival compared with controls. Conclusion: Endotoxin neutralizing protein significantly reduces mortality from Gramnegative sepsis in an antibiotic-treatment model of E. coli peritonitis and bacteremia in rats, mediated by a neutralization of the biological effects of endotoxin.