Journal of Clinical & Experimental Pharmacology

Abstract

HMGB1 Release by C5a Anaphylatoxin is an Effective Target for Sepsis Treatment

Noriko Okada, Masaki Imai, Alan Okada, Fumiko Ono and Hidechika Okada

Antibodies to C5a have proven to be effective in treating experimental septic primate models. A 17 amino acid peptide (ASGAPAPGPAGPLRPMF) named PepA binds to C5a and prevents complement-mediated lethal shock in rats. AcPepA harboring an acetyl group at the N-terminal alanine showed increased inhibitory activity against C5a. Cynomolgus monkeys destined to expire from a lethal dose of bacterial endotoxin (4 mg/kg) were rescued by intravenous administration of AcPepA. AcPepA could have interfered with the ability of C5a to stimulate C5L2 which is responsible for HMGB1 release and stimulation of TLR4 as an endogeneous ligand with LPS behavior. The suppression of HMGB1 release by AcPepA administration to LPS-shock monkeys is likely responsible for rescuing the animals.