Recombinant endotoxin neutralizing protein improves survival from Escherichia coli sepsis in rats.
作者信息
Nelson D, Kuppermann N, Fleisher G R, Hammer B K, Thompson C M, Garcia C T, Novitsky T J, Parsonnet J, Onderdonk A, Siber G R
机构信息
Department of Medicine, Children's Hospital, Boston, MA 02115.
出版信息
Crit Care Med. 1995 Jan;23(1):92-8. doi: 10.1097/00003246-199501000-00017.
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. coli 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 Gram-negative sepsis in an antibiotic-treatment model of E. coli peritonitis and bacteremia in rats, mediated by a neutralization of the biological effects of endotoxin.
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