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Critical Care Research and Practice
Volume 2012, Article ID 427607, 8 pages
http://dx.doi.org/10.1155/2012/427607
Review Article

Manipulation of the Complement System for Benefit in Sepsis

1Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, P.O. Box 5602, Ann Arbor, MI 48109-5602, USA
2Department of Anesthesiology and Intensive Care Medicine, University Hospital Jena, 07747 Jena, Germany

Received 28 September 2011; Accepted 6 November 2011

Academic Editor: Howard L. Corwin

Copyright © 2012 Peter A. Ward et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

There is evidence in sepsis, both in rodents and in humans, that activation of the complement system results in excessive production of C5a, which triggers a series of events leading to septic shock, multiorgan failure, and lethality. In rodents following cecal ligation and puncture (CLP), which induces polymicrobial sepsis, in vivo blockade of C5a using neutralizing antibodies dramatically improved survival, reduced apoptosis of lymphoid cells, and attenuated the ensuing coagulopathy. Based on these data, it seems reasonable to consider therapeutic blockade of C5a in humans entering into sepsis and septic shock. Strategies for the development of such an antibody for use in humans are presented.