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Protective effects of C5a blockade in sepsis

Nature Medicine volume 5, pages 788–792 (1999)Cite this article

Abstract

Sepsis in humans is a difficult condition to treat and is often associated with a high mortality rate. In this study, we induced sepsis in rats using cecal ligation and puncture (CLP). In rats depleted of the complement factor C3, CLP led to very short survival times (about 4 days). Of the rats that underwent CLP ('CLP rats') that were C3-intact and treated with preimmune IgG, most (92%) were dead by 7 days. Blood neutrophils from these rats contained on their surfaces the powerful complement activation product C5a. This group had high levels of bacteremia, and their blood neutrophils when stimulated in vitro had greatly reduced production of H2O2, which is known to be essential for the bactericidal function of neutrophils. In contrast, when companion CLP rats were treated with IgG antibody against C5a, survival rates were significantly improved, levels of bacteremia were considerably reduced, and the H2O2 response of blood neutrophils was preserved. Bacterial colony-forming units in spleen and liver were very high in CLP rats treated with preimmune IgG and very low in CLP rats treated with IgG antibody against C5a, similar to values obtained in rats that underwent 'sham' operations (without CLP). These data indicate that sepsis causes an excessive production of C5a, which compromises the bactericidal function of neutrophils. Thus, C5a may be a useful target for the treatment of sepsis.

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Figure 1: Rates of survival in rats after cecal ligation and puncture (CLP).
Figure 2: Bacterial colony-forming units (CFU) in blood.
Figure 3: Bacterial colony-forming units (CFU) in spleen and liver.
Figure 4: H2O2 production by blood neutrophils.

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Authors and Affiliations

  1. Department of Trauma Surgery, University of Freiburg Medical School, Freiburg/Breisgau, Germany, D-79106

    Boris J. Czermak, Markus Huber-Lang, Nicolas M. Bless, Hagen Schmal & Hans Peter Friedl

  2. Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, Michigan

    Boris J. Czermak, Vidya Sarma, Carl L. Pierson, Roscoe L. Warner, Markus Huber-Lang & Peter A. Ward

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  1. Boris J. Czermak
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Correspondence to Peter A. Ward.

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Czermak, B., Sarma, V., Pierson, C. et al. Protective effects of C5a blockade in sepsis. Nat Med 5, 788–792 (1999). https://doi.org/10.1038/10512

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