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

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.

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 α (TNFα) and interleukin‐10 (IL‐10) compared with those from mice treated with Crry‐Ig. Lower steady‐state messenger RNA (mRNA) levels for TNFα, interferon‐γ (IFNγ), IL‐18, and IL‐6 were observed in the joints of anti‐C5–treated mice, and for IFNγ and IL‐6 in mice receiving Crry‐Ig, all in comparison with PBS‐treated mice. However, mRNA levels for IL‐1β and TNFα were lower in the joints after treatment with anti‐C5 compared with Crry‐Ig.

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‐1β and TNFα mRNA in the joints.