Recent advances in therapy of sepsis: Focus on recombinant bactericidal/permeability-increasing protein (BPI)

Abstract

The inability to reduce the high mortality due to overwhelming bacterial infection and sepsis has prompted a search for new therapeutic agents. Among these may be a wide range of endogenous antibiotic polypeptides that are prominent components of effective antimicrobial host defences. One of these polypeptide antibiotics is the bactericidal/permeability-increasing protein (BPI), a protein of approximately 55kD which is present in human and other mammalian neutrophils. BPI is toxic for Gram-negative bacteria and binds to endotoxin, resulting in its clearance and neutralisation. A recombinant 21 kD N-terminal BPI fragment is at least as active as holo-BPI and protects both animals and humans against the effects of Gram-negative infections and their complications. Phase II/III clinical trials in fulminant paediatric meningococcaemia, haemorrhagic trauma, hepatectomy and severe peritoneal infections are in progress.