Accelerated onset of collagen-induced arthritis by remote inflammation

Clin Exp Immunol. 1994 Aug;97(2):204-11. doi: 10.1111/j.1365-2249.1994.tb06069.x.


Collagen-induced arthritis (CIA) in DBA-1 lac/J mice often has a low incidence, with gradual disease expression occurring over a broad time span (between days 35 and 70). The exact mechanisms underlying spontaneous expression are still poorly understood, although it is evident that some inflammatory cytokines like IL-1, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) are potent accelerators. We have investigated whether we could trigger collagen type II-driven inflammation by: (i) enhancing anti-collagen type II (CII) antibodies, or (ii) a non-related inflammatory process. Male DBA-1 lac/J mice were immunized with 100 micrograms bovine type II collagen in Freund's complete adjuvant (FCA), resulting in a low disease expression at day 28. Addition of anti-CII antibodies slightly enhanced the expression of CIA. Zymosan (3 mg), given intraperitoneally, induced consistent expression of CIA after 1 week, whereas a retarded onset was noted with higher dosages. Local injection of a low dose of Zymosan (60 micrograms) in the knee joint, clearly potentiated the expression of CIA at that particular site. Higher concentrations not only elicited prolonged CIA expression at the injection site, but also induced marked CIA in the draining ankle joint. In contrast, intra-articular injection of Zymosan in nonimmunized DBAs or methylated bovine serum albumin (mBSA)/FCA-immunized controls only induced transient joint inflammation. The nature of the highly erosive CIA was confirmed histologically, and could easily be discriminated from the reversible changes induced with Zymosan. Our data indicate that latent autoimmune reactions may come to expression at the moment of non-specific inflammation, even at a remote site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Arthritis, Experimental / immunology*
  • Collagen / immunology
  • Inflammation / immunology*
  • Interleukin-1 / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Tumor Necrosis Factor-alpha / immunology
  • Zymosan


  • Antibodies
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Collagen
  • Zymosan