Protective Effect of a Recombinant Amino-Terminal Fragment of Bactericidal/Permeability-Increasing Protein in Experimental Endotoxemia

• Published in: The Journal of infectious diseases Vol. 168; no. 5; pp. 1307 - 1310
• Main Authors: Kohn, Fred R., Ammons, W. Steve, Horwitz, Arnold, Grinna, Lynn, Theofan, Georgia, Weickmann, Joachim, Kung, Ada H. C.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.11.1993; University of Chicago Press
• Subjects: Actinomycin; Animals; Antimicrobial Cationic Peptides; Bacterial diseases; Biological and medical sciences; Blood Proteins - therapeutic use; Concise Communications; Cytokines; Dactinomycin - pharmacology; Endotoxemia; Escherichia coli; Experimental bacterial diseases and models; Gram-Negative Bacterial Infections - drug therapy; Infectious diseases; Interleukin-1 - blood; Lipopolysaccharides; Lipopolysaccharides - adverse effects; Male; Medical sciences; Membrane Proteins; Mice; Mice, Inbred Strains; Peptide Fragments - therapeutic use; Protective effects; Proteins; Recombinant Proteins - therapeutic use; Sepsis; Shock, Septic - chemically induced; Shock, Septic - drug therapy; Tumor Necrosis Factor-alpha - analysis; Tumor necrosis factors; Vehicles; Rodentia; Permeability; N terminal peptide; Proteins; Prevention; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Mouse; Animal; Recombinant protein; Antibacterial agent; Endotoxemia
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/168.5.1307

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 oflethal endotoxemia. Systemic administration ofrBPI23 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-α and interleukin-1α, 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.