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.