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.


METHODS
Prospective, controlled animal trial.


METHODS
Hospital animal research laboratory.


METHODS
Wistar rats, treated with gentamicin 1 hr after challenge with intraperitoneal E. coli O18ac.


METHODS
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.


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.


CONCLUSIONS
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.
Nelson
D
D
Department of Medicine, Children's Hospital, Boston, MA 02115.
Kuppermann
N
N
Fleisher
G R
GR
Hammer
B K
BK
Thompson
C M
CM
Garcia
C T
CT
Novitsky
T J
TJ
Parsonnet
J
J
Onderdonk
A
A
Siber
G R
GR
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D016470:Bacteremia / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000628:therapy; D004731:Endotoxins / Q000097:blood; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D005839:Gentamicins / Q000627:therapeutic use; D007447:Invertebrate Hormones / Q000627:therapeutic use*; D008297:Male; D010538:Peritonitis / Q000097:blood / Q000188:drug therapy / Q000401:mortality / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D004731:Endotoxins; D005839:Gentamicins; D007447:Invertebrate Hormones; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C034705:antilipopolysaccharide factor (Limulus)