title: Human neutrophil bactericidal/permeability-increasing protein reduces mortality rate from endotoxin challenge: a placebo-controlled study.
abstract: OBJECTIVE
  To study the toxicology and pharmacology of the endotoxin-neutralizing agent, bactericidal/permeability-increasing protein.
  
  
  METHODS
  Prospective, randomized, placebo-controlled laboratory study.
  
  
  METHODS
  Academic research laboratory.
  
  
  METHODS
  CD-1 mice (n = 259); Sprague Dawley rats (n = 26); New Zealand White rabbits (n = 19).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Bactericidal/permeability-increasing protein is a potent antiendotoxin that neutralizes endotoxin in vivo and prevents mortality in animal models of lethal endotoxemia.
authors.affiliation: Cleveland Clinic Foundation, OH.
authors.forename: C J
authors.initials: CJ
authors.lastname: Fisher
authors.forename: M N
authors.initials: MN
authors.lastname: Marra
authors.forename: J E
authors.initials: JE
authors.lastname: Palardy
authors.forename: C R
authors.initials: CR
authors.lastname: Marchbanks
authors.forename: R W
authors.initials: RW
authors.lastname: Scott
authors.forename: S M
authors.initials: SM
authors.lastname: Opal
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004731:Endotoxins / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008050:Lipid A / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009504:Neutrophils / Q000187:drug effects*; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D008050:Lipid A; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein