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Updated: May 23, 2026

Design of Cecal Ligation and Puncture and Intranasal Infection Dual Model of Sepsis-Induced Immunosuppression
Published on: June 15, 2019
Manipulation of the complement system for benefit in sepsis.
Peter A Ward1, Ren-Feng Guo, Niels C Riedemann
1Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, P.O. Box 5602, Ann Arbor, MI 48109-5602, USA.
Blocking C5a, a complement system protein, significantly improves survival in rodent sepsis models. This suggests C5a blockade is a promising therapeutic strategy for human sepsis and septic shock.
Area of Science:
- Immunology
- Critical Care Medicine
- Molecular Biology
Background:
- Sepsis involves excessive complement system activation, leading to harmful C5a production.
- C5a triggers events causing septic shock, organ failure, and death in both rodents and humans.
Purpose of the Study:
- To investigate the therapeutic potential of blocking C5a in sepsis.
- To present strategies for developing C5a-blocking antibodies for human use.
Main Methods:
- Utilized cecal ligation and puncture (CLP) to induce polymicrobial sepsis in rodents.
- Administered in vivo blockade of C5a using neutralizing antibodies.
Main Results:
- C5a blockade dramatically improved survival rates in rodent sepsis models.
- Reduced apoptosis of lymphoid cells and attenuated coagulopathy were observed.
- Demonstrated the efficacy of C5a inhibition in a preclinical sepsis setting.
Conclusions:
- Therapeutic blockade of C5a is a viable strategy for treating human sepsis and septic shock.
- Further development of C5a-neutralizing antibodies is warranted for clinical application.
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