Mechanisms of effects of complement inhibition in murine collagen-induced arthritis
In: Arthritis and rheumatism, Jg. 46 (2002), Heft 11, S. 3065-3075
Online
academicJournal
- print, 40 ref
Zugriff:
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 a (TNFa) and interleukin-10 (IL-10) compared with those from mice treated with Crry-Ig. Lower steady-state messenger RNA (mRNA) levels for TNFa, 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 TNFa 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-1β and TNFa mRNA in the joints.
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Mechanisms of effects of complement inhibition in murine collagen-induced arthritis
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Autor/in / Beteiligte Person: | BANDA, Nirmal K ; KRAUS, Damian ; VONDRACEK, Andrea ; HUYNH, Long H ; BENDELE, Alison ; HOLERS, V. Michael ; AREND, William P |
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Zeitschrift: | Arthritis and rheumatism, Jg. 46 (2002), Heft 11, S. 3065-3075 |
Veröffentlichung: | Hoboken , NJ: Wiley, 2002 |
Medientyp: | academicJournal |
Umfang: | print, 40 ref |
ISSN: | 0004-3591 (print) |
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