Human neutrophil bactericidal/permeability-increasing protein reduces mortality rate from endotoxin challenge: a placebo-controlled study

• Published in: Critical care medicine Vol. 22; no. 4; p. 553
• Main Authors: Fisher, Jr, C J, Marra, M N, Palardy, J E, Marchbanks, C R, Scott, R W, Opal, S M
• Format: Journal Article
• Language: English
• Published: United States 01-04-1994
• Subjects: Animals; Antimicrobial Cationic Peptides; Blood Proteins - administration & dosage; Blood Proteins - pharmacokinetics; Blood Proteins - toxicity; Endotoxins - antagonists & inhibitors; Female; Humans; Injections, Intravenous; Lipid A - metabolism; Membrane Proteins; Mice; Neutrophils - drug effects; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Shock, Septic - drug therapy; Shock, Septic - metabolism; Shock, Septic - mortality
• ISSN: 0090-3493
• DOI: 10.1097/00003246-199404000-00008

To study the toxicology and pharmacology of the endotoxin-neutralizing agent, bactericidal/permeability-increasing protein.
Prospective, randomized, placebo-controlled laboratory study.
Academic research laboratory.
CD-1 mice (n = 259); Sprague Dawley rats (n = 26); New Zealand White rabbits (n = 19).
Pharmacokinetics of intravenously injected bactericidal/permeability-increasing protein was assessed in mice. Toxicology was tested in mice and rats. Efficacy of intravenously administered bactericidal/permeability-increasing protein as an endotoxin-neutralizing agent was tested in mice, rats, and rabbits.
Administration of a single 10-mg/kg bolus injection of bactericidal/permeability-increasing protein resulted in no alterations in hematologic, renal, or hepatic function, activity level, or weight gain in animals observed over a 7-day study period. A single bolus injection (10 mg/kg) of bactericidal/permeability-increasing protein protected 15 of 16 mice from a lethal endotoxin challenge (mortality rate 1/16 [6.25%]) compared with a 100% (16/16) mortality rate in the saline-treated controls (p < .001). Bactericidal/permeability-increasing protein administered up to 1 hr after endotoxin provided significant protection against lethal endotoxin challenge. Furthermore, bactericidal/permeability-increasing protein reduced the induration and dermal necrosis observed in the localized dermal Shwartzman reaction.
Bactericidal/permeability-increasing protein is a potent antiendotoxin that neutralizes endotoxin in vivo and prevents mortality in animal models of lethal endotoxemia.