alexa HMGB1 Release by C5a Anaphylatoxin is an Effective Target for Sepsis Treatment
ISSN: 2161-1459

Journal of Clinical & Experimental Pharmacology
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Review Article

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

Noriko Okada1, Masaki Imai1, Alan Okada2, Fumiko Ono3 and Hidechika Okada1,2*

1Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan

2Choju Medical Institute, Fukushimura Hospital, Tnoyohashi 411-8124, Japan

3Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba 305-0843, Japan

*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.


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