Protective effect of a recombinant amino-terminal fragment of bactericidal/permeability-increasing protein in experimental endotoxemia.

Abstract	Bactericidal/permeability-increasing protein (BPI), a cationic protein found in neutrophil granules, binds with high affinity to gram-negative bacterial lipopolysaccharide (LPS) and can inhibit its actions in vitro. The in vivo efficacy of a recombinant 23-kDa amino-terminal LPS-binding fragment of BPI (rBPI23) was assessed in a mouse model of lethal endotoxemia. Systemic administration of rBPI23 protected actinomycin D-sensitized mice from lethal LPS (Escherichia coli O111:B4) challenge in a dose-dependent manner, with almost complete protection at the highest dose (10 mg/kg; 93% survival vs. 13% in vehicle-treated controls). Surviving rBPI23-treated animals did not show histopathologic signs of tissue damage evident in control animals that had died after LPS challenge. rBPI23 also attenuated the LPS-induced elevation in serum levels of tumor necrosis factor-alpha and interleukin-1 alpha, mediators believed to be involved in the pathogenesis of endotoxemia and sepsis. Thus, rBPI23 may be a potential new therapeutic agent for the treatment of gram-negative bacterial infection and sepsis.
Authors	F R Kohn, W S Ammons, A Horwitz, L Grinna, G Theofan, J Weickmann, A H Kung
Journal	The Journal of infectious diseases (J Infect Dis) Vol. 168 Issue 5 Pg. 1307-10 (Nov 1993) ISSN: 0022-1899 [Print] United States
PMID	8228369 (Publication Type: Journal Article)
Chemical References	Antimicrobial Cationic Peptides Blood Proteins Interleukin-1 Lipopolysaccharides Membrane Proteins Peptide Fragments Recombinant Proteins Tumor Necrosis Factor-alpha bactericidal permeability increasing protein Dactinomycin
Topics	Animals Antimicrobial Cationic Peptides Blood Proteins (therapeutic use) Dactinomycin (pharmacology) Gram-Negative Bacterial Infections (drug therapy) Interleukin-1 (blood) Lipopolysaccharides (adverse effects) Male Membrane Proteins Mice Mice, Inbred Strains Peptide Fragments (therapeutic use) Recombinant Proteins (therapeutic use) Shock, Septic (chemically induced, drug therapy) Tumor Necrosis Factor-alpha (analysis)

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