Blockade of complement activation product C5a activity using specific antibody attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of colitis

Lab Invest. 2011 Mar;91(3):472-83. doi: 10.1038/labinvest.2010.183. Epub 2010 Nov 22.


Complement represents a chief component of innate immunity in host defense. However, excessive complement activation has been involved in the pathogenesis of inflammatory diseases. In this study, we investigated the contribution of complement to intestinal pathology of patients and rodents with inflammatory bowel disease. The expression of complement effectors (C3a and C3) was increased remarkably in inflamed colons of IBD patients compared with those of normal counterparts. In accordance with this, the sustained activation of complement in serum and colon (including elevated C3a and C5a levels, enhanced hemolytic activity, downregulated expression of C5a receptors) was observed, following the establishment of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, which peaked at 24 h. Mice pretreated with neutralizing anti-C5a antibodies (-2, 0, and 2 days after TNBS instillation) had significantly reduced weight loss and improved macroscopic/microscopic scores, comparable to the efficacy of prednisolone treatment. Strikingly, treatment with anti-C5a at 24 h after TNBS instillation showed remarkable therapeutic effects, whereas prednisolone did not. The efficacy of anti-C5a administration was associated with decreased release of proinflammatory chemokines and cytokines, inhibition of infiltration of neutrophils into colons, and enhanced Th2 response. These findings suggest a disease-promoting role of complement, particular C5a, in the pathology of TNBS-induced colitis in mice, indicating possible therapeutic potentials for C5a-specific antibody in IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / therapeutic use*
  • Colitis / immunology
  • Colitis / pathology*
  • Colitis / prevention & control*
  • Colitis / therapy
  • Colon / immunology*
  • Colon / metabolism
  • Colon / pathology*
  • Complement Activation / immunology
  • Complement C5a / antagonists & inhibitors*
  • Complement C5a / immunology
  • Cytokines / blood
  • Cytokines / metabolism
  • Humans
  • Immunotherapy
  • Inflammatory Bowel Diseases / blood
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology*
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neutrophil Infiltration / immunology
  • RNA, Messenger / metabolism
  • Receptor, Anaphylatoxin C5a / genetics
  • Receptor, Anaphylatoxin C5a / metabolism
  • Severity of Illness Index
  • Th2 Cells / immunology
  • Time Factors
  • Trinitrobenzenesulfonic Acid / toxicity


  • Antibodies, Neutralizing
  • Cytokines
  • RNA, Messenger
  • Receptor, Anaphylatoxin C5a
  • Complement C5a
  • Trinitrobenzenesulfonic Acid