Mechanisms of effects of complement inhibition in murine collagen-induced arthritis

Arthritis Rheum. 2002 Nov;46(11):3065-75. doi: 10.1002/art.10591.


Objective: To determine the mechanisms of amelioration of collagen-induced arthritis (CIA) in DBA/1J mice by inhibition of complement activation.

Methods: Mice received 2 intradermal injections of bovine type II collagen (CII), on days 0 and 21. From day 21 (immediately after the second injection of CII) through day 35, mice received intraperitoneal injections of either phosphate buffered saline (PBS), a monoclonal mouse antibody to murine C5 (anti-C5 antibody), or the C3 convertase inhibitor Crry-Ig.

Results: On days 30 and 32, the clinical disease activity score was lower in mice treated with anti-C5 antibody than in those treated with Crry-Ig. Histopathologic evidence of joint damage was 75% lower in the mice treated with anti-C5 antibody than in those treated with either PBS or Crry-Ig. Spleen cells from mice receiving either form of complement inhibition exhibited decreased CII-stimulated proliferation, whereas increased proliferative responses were exhibited by lymph node cells from mice treated with Crry-Ig. Treatment with anti-C5 antibody decreased production of IgG1 anticollagen antibody, while production of IgG2a antibody was inhibited by both complement inhibitory treatments. CII-stimulated spleen cells from anti-C5-treated mice produced lower levels of tumor necrosis factor alpha (TNFalpha) and interleukin-10 (IL-10) compared with those from mice treated with Crry-Ig. Lower steady-state messenger RNA (mRNA) levels for TNFalpha, interferon-gamma (IFNgamma), IL-18, and IL-6 were observed in the joints of anti-C5-treated mice, and for IFNgamma and IL-6 in mice receiving Crry-Ig, all in comparison with PBS-treated mice. However, mRNA levels for IL-1beta and TNFalpha were lower in the joints after treatment with anti-C5 compared with Crry-Ig.

Conclusion: These results indicate that inhibition of complement in CIA leads to decreased production of IgG2a antibody and suppressed CII-induced spleen cell proliferation. The greater inhibitory effects on CIA of anti-C5 antibody in comparison with Crry-Ig may be attributable primarily to decreased levels of IL-1beta and TNFalpha mRNA in the joints.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / immunology*
  • Autoantibodies / immunology
  • Collagen
  • Complement Activation / immunology*
  • Complement C3-C5 Convertases / antagonists & inhibitors*
  • Complement C5 / immunology*
  • Interferon-gamma / biosynthesis
  • Interleukin-1 / analysis
  • Interleukin-10 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Male
  • Mice
  • Mice, Inbred DBA
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Autoantibodies
  • Complement C5
  • Interleukin-1
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma
  • Collagen
  • Complement C3-C5 Convertases