PROTECTIVE EFFECTS OF AN N-TERMINAL FRAGMENT OF BACTERICIDAL PERMEABILITY-INCREASING PROTEIN IN RODENT MODELS OF GRAM-NEGATIVE SEPSIS - ROLE OF BACTERICIDAL PROPERTIES

Effects of an N-terminal fragment of bactericidal/permeability increasing protein (rBPI(21)) on bacterial infections were determined, Intravenous (iv) rBPI(21) increased survival and reduced bacteremia in rats after an iv injection of Escherichia coli O7:K1 bacteria, rBPI(21) inhibited the rise in tumor necrosis factor-alpha resulting from challenge with 2 strains of E. coli. Intraperitoneal (ip) injection of rBPI(21) increased survival of mice after ip injection of E. coli O7:K1 and Pseudomonas aeruginosa and reduced bacteria in peritoneal lavage fluid and blood and inhibited cytokine production in response to E. coli. rBPI(21) alone did not protect mice challenged with E. coli O111:B4 but was protective and reduced bacterial counts when administered in combination with the antibiotic cefamandole. The data show that protection with rBPI(21) is associated with reductions in bacterial counts and is enhanced by antibiotics. Bactericidal activity, in addition to antiendotoxin activity, is involved in the efficacy of rBPI(21) in models of gram-negative infection.