Effect of a recombinant endotoxin-neutralizing protein on endotoxin shock in rabbits

Crit Care Med. 1994 Aug;22(8):1211-8. doi: 10.1097/00003246-199408000-00003.

Abstract

Objectives: 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.

Design: Controlled animal trial.

Setting: Animal research laboratory.

Subjects: A total of 112 New Zealand white rabbits were studied.

Interventions: 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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Antimicrobial Cationic Peptides
  • Arthropod Proteins
  • Blood Gas Analysis
  • Blood Pressure / drug effects
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Endotoxins / blood
  • Escherichia coli
  • Escherichia coli Infections / blood
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Infections / mortality
  • Escherichia coli Infections / physiopathology
  • Invertebrate Hormones / pharmacology
  • Invertebrate Hormones / therapeutic use*
  • Lethal Dose 50
  • Lipopolysaccharides / blood
  • Premedication / methods*
  • Rabbits
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use*
  • Shock, Septic / blood
  • Shock, Septic / drug therapy*
  • Shock, Septic / mortality
  • Shock, Septic / physiopathology
  • Survival Rate
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Arthropod Proteins
  • Endotoxins
  • Invertebrate Hormones
  • Lipopolysaccharides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • antilipopolysaccharide factor (Limulus)
  • endotoxin, Escherichia coli