Protective effect of bactericidal/permeability-increasing protein (rBPI(21)) in baboon sepsis is related to its antibacterial, not antiendotoxin, properties

Objective and Summary Background Data The recombinant fragment of bacterici dal/permeability-increasing protein, rBPI(21) has potent bactericidal activ ity against gram-negative bacteria as well as antiendotoxin (lipopolysaccha ride [LPS]) action. On the basis of these activities. the authors sought to discover whether rBPI(21) would be protective in baboons with live Escheri chia coil-induced sepsis and whether the potential protective effects of rB PI(21) (together with antibiotics) would be more closely related to its ant ibacterial or LPS-neutralizing effects. Methods In a prospective, randomized, placebo-controlled subchronic laborat ory study, the efficacy of rBPI(21) or placebo was studied over 72 hours in chronically instrumented male baboons infused with live E. coil under anti biotic therapy. Results Intravenous rBPI(21) attenuated sepsis-related organ failure and in creased survival significantly. Bacteremia was significantly reduced in the rBPI(21) group at 2 hours after the start of the E. coil infusion, whereas circulating. LPS was less affected. The in vivo formation of tumor necrosi s factor was significantly suppressed by the rBPI(21) treatment regimen. Mi crocirculation and organ function were improved. Conclusions In baboon live E. coli sepsis,the salutary effect of rBPI(21) r esults from a more prevalent antibacterial than antiendotoxin activity.