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 pr operties and also binds lipopolysaccharide (LPS). The ability of a rec ombinant amino-terminal fragment of BPI to protect mice from death aft er challenge with a number of different strains of Escherichia coli wa s tested. BPI prevented death in animals challenged with the J5 rough strain but not with smooth strains O111:B4 and O7K1. Protection was as sociated with a reduction in serum LPS and tumor necrosis factor-ct le vels but not with reduction in blood bacterial counts. BPI was effecti ve 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 similar to 1000-fold higher b lood bacterial count compared with J5. Thus, BPI is a promising therap y in the treatment of gram-negative septic shock, although the range o f organisms against which it is effective remains to be determined.