Activity of lipopolysaccharide-binding protein-bactericidal/permeability-increasing protein fusion peptide in an experimental model of Pseudomonas sepsis.

A chimeric protein consisting of the N-terminal domain of lipopolysaccharide-binding protein and the C-terminal domain of bactericidal/permeability-increasing protein demonstrated a dose-dependent survival benefit (P 50.001) and reduced endotoxin levels (P< 0.01) in neutropenic rats withPseudomonas aeruginosa sepsis. This lipopolysaccharide-binding protein‐bactericidal/permeability-increasing peptide has favorable pharmacokinetics and antiendotoxin properties which may be of value for human sepsis. Currenttherapeuticoptionsforgram-negativebacterialsepsis are limited to antimicrobial agents, hemodynamic support, and management of sepsis-induced organ dysfunction (4). Efforts to interfere directly in the pathophysiologic mechanisms whichunderliethesepticprocesshaveyieldedinconsistentand largely disappointing results. Antiendotoxin monoclonal antibodies (11, 18), anticytokine therapies (1, 6, 8), and other anti-inflammatory strategies (5, 24) have not proven to be of sufficient benefit to warrant approval as standard adjunctive therapies for human sepsis. Despite these setbacks, it is anticipated that refinements in clinical trial design and innovations in the synthesis of more potent therapeutic agents will lead to significant advances in the treatment of sepsis in the future. A naturally occurring endotoxin-bindingandneutralizingproteinwhichmayproveto be particularly effective in endotoxemic states is bactericidal/