Effect of a recombinant endotoxin-neutralizing protein on endotoxin shock in rabbits.
OBJECTIVE
Limulus anti-lipopolysaccharide factor, an 11.8-kilodalton peptide isolated from amebocytes of Limulus polyphemus inhibits the biologic activities of endotoxin in vitro, including gelation of Limulus amebocyte lysate. A recombinant version of Limulus anti-lipopolysaccharide factor, termed endotoxin neutralizing protein, has now been expressed in yeast. Endotoxin-neutralizing protein was evaluated for its potential prophylactic and therapeutic effects in rabbits challenged with Escherichia coli endotoxin.


METHODS
Controlled animal trial.


METHODS
Animal research laboratory.


METHODS
A total of 112 New Zealand white rabbits were studied.


METHODS
Rabbits were challenged with an LD80 dose of E. coli endotoxin (100 micrograms/kg); control animals (n = 52) were treated with saline solution at the time of endotoxin challenge; experimental animals received endotoxin-neutralizing protein 2.5 mg/kg prechallenge (n = 20), 5.0 mg/kg prechallenge (n = 20), or 5.0 mg/kg 30 mins postchallenge (n = 20).
Garcia
C
C
Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115.
Saladino
R
R
Thompson
C
C
Hammer
B
B
Parsonnet
J
J
Wainwright
N
N
Novitsky
T
T
Fleisher
G R
GR
Siber
G
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D007447:Invertebrate Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000097:blood; D011292:Premedication / Q000379:methods*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D004731:Endotoxins; D007447:Invertebrate Hormones; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C034705:antilipopolysaccharide factor (Limulus); C044101:endotoxin, Escherichia coli