Protective effect of bactericidal/permeability-increasing protein (rBPI21) in baboon sepsis is related to its antibacterial, not antiendotoxin, properties.

Objective and Summary Background Data The recombinant fragment of bactericidal/permeability-increasing protein, rBPl 21 , has potent bactericidal activity against gram-negative bacteria as well as antiendotoxin (lipopolysaccharide [LPS]) action. On the basis of these activities, the authors sought to discover whether rBPl 21 would be protective in baboons with live Escherichia coli-induced sepsis and whether the potential protective effects of rBPl 21 (together with antibiotics) would be more closely related to its antibacterial or LPS-neutralizing effects. Methods In a prospective, randomized, placebo-controlled subchronic laboratory study, the efficacy of rBPl 21 or placebo was studied over 72 hours in chronically instrumented male baboons infused with live E. coli under antibiotic therapy. Results Intravenous rBPl 21 attenuated sepsis-related organ failure and increased survival significantly. Bacteremia was significantly reduced in the rBPl 21 group at 2 hours after the start of the E. coli infusion, whereas circulating LPS was less affected. The in vivo formation of tumor necrosis factor was significantly suppressed by the rBPl 21 treatment regimen. Microcirculation and organ function were improved. Conclusions In baboon live E. coli sepsis, the salutary effect of rBPl 21 results from a more prevalent antibacterial than antiendotoxin activity.