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 i n rats. Design: Prospective, controlled animal trial. Setting: Hospita l animal research laboratory. Subjects: Wistar rats, treated with gent amicin 1 hr after challenge with intraperitoneal E. coli O18ac. Interv entions: The animals received a recombinant endotoxin neutralizing pro tein, in doses of 5, 25, or 50 mg/kg, either 30 or 60 mins after chall enge; controls received saline. Measurements and Main Results: Geometr ic mean serum endotoxin concentrations in endotoxin neutralizing prote in-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 protei n 30 mins after E. cell challenge had significant improvements in surv ival compared with controls. Animals treated with 50 mg/kg of endotoxi n neutralizing protein 60 mins after E. coli challenge had significant improvements in survival compared with controls. Conclusion: Endotoxi n neutralizing protein significantly reduces mortality from Gramnegati ve sepsis in an antibiotic-treatment model of E. coli peritonitis and bacteremia in rats, mediated by a neutralization of the biological eff ects of endotoxin.