Protective effects of a recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in an animal model of gram-negative sepsis.
Bactericidal/permeability-increasing protein (BPI) has bactericidal properties and also binds lipopolysaccharide (LPS). The ability of a recombinant amino-terminal fragment of BPI to protect mice from death after challenge with a number of different strains of Escherichia coli was tested. BPI prevented death in animals challenged with the J5 rough strain but not with smooth strains O111:B4 and O7K1. Protection was associated with a reduction in serum LPS and tumor necrosis factor-alpha levels but not with reduction in blood bacterial counts. BPI was effective at protecting against death in mice injected with purified O111:B4 LPS. Lack of protection after injection with live O111:B4 and O7K1 may be due to production by these models of approximately 1000-fold higher blood bacterial count compared with J5. Thus, BPI is a promising therapy in the treatment of gram-negative septic shock, although the range of organisms against which it is effective remains to be determined.
Evans
T J
TJ
Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, London, United Kingdom.
Carpenter
A
A
Moyes
D
D
Martin
R
R
Cohen
J
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli / Q000254:growth & development; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005688:Galactosamine / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C021623:bactericidal permeability increasing protein; D005688:Galactosamine