Prospects for use of recombinant BPI in the treatment of gram-negative bacterial infections

The bactericidal/permeability-increasing protein (BPI), a potent cytotoxin specific for Gram-negative bacteria and an endotoxin-neutralizing agent, is a major component of the antimicrobial arsenal of mammalian polymorphonuclear leukocytes. The antibacterial and endotoxin-neutralizing activities of the N-terminal portion (approximately 25 kDa) of BPI are at least equal to those of the holoprotein (approximately 50 kDa). Recombinant N-terminal fragments of BPI are antibacterial and inhibit host cell responses to endotoxin in whole blood ex vivo and in animal experiments. BPI administered to both animals and man is apparently nontoxic and nonimmunogenic and acts synergistically with some antibiotics. Thus, the prospects for the therapeutic use of bioactive BPI fragments in serious Gram-negative bacterial infections are highly encouraging.