HMGB1 Release by C5a Anaphylatoxin is an Effective Target for Sepsis Treatment
- *Corresponding Author:
- Dr. Hidechika Okada
Choju Medical Institute
Fukushimura Hospital, Noyori-cho
Toyohashi 441-8124, Japan
E-mail: [email protected]
Received date: May 07, 2012; Accepted date: July 06, 2012; Published date: July 07, 2012
Citation: Okada N, Imai M, Okada A, Ono F, Okada H (2012) HMGB1 Release by C5a Anaphylatoxin is an Effective Target for Sepsis Treatment. Clin Exp Pharmacol 2:114. doi: 10.4172/2161-1459.1000114
Copyright: ©2012 Okada N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.