Chronic relapsing homologous collagen-induced arthritis in DBA/1 mice as a model for testing disease-modifying and remission-inducing therapies

Arthritis Rheum. 2001 May;44(5):1215-24. doi: 10.1002/1529-0131(200105)44:5<1215::AID-ANR206>3.0.CO;2-#.


Objective: To test whether the chronic relapsing arthritis induced by immunizing DBA/1 mice with homologous type II collagen is a valuable model for testing disease-modifying antiarthritic drugs.

Methods: Six-week-old male DBA/1 mice were immunized with murine type II collagen in Freund's complete adjuvant, resulting in a chronic relapsing polyarthritis in >80% of the mice 4 weeks after immunization. At the onset of clinical arthritis, mice were treated for 4 weeks with different treatments, including anti-tumor necrosis factor (anti-TNF) and antiinterleukin-12 (anti-IL-12) antibodies, salbutamol, or indomethacin. Alternatively, treatment was administered as a pulse at the beginning of clinical arthritis. Pulse treatments tested included anti-CD3 in combination with anti-TNF, anti-TNF alone, and anti-CD4, either alone or in combination with anti-TNF. After 4 weeks of arthritis, mice were killed and hind paws were assessed histologically for joint damage.

Results: Anti-TNF and salbutamol both suppressed clinical arthritis more effectively than indomethacin and, moreover, protected the joints from damage, whereas indomethacin did not. Anti-IL-12 treatment initiated after the onset of clinical symptoms accelerated disease. Pulse therapy with anti-CD3 plus anti-TNF was found to induce remission, clinically as well as histologically, whereas a pulse with either anti-CD4, anti-TNF, or the combination of anti-CD4 plus anti-TNF was less effective.

Conclusion: Chronic relapsing homologous collagen-induced arthritis is a valuable model for identifying remission-inducing antiarthritic drugs and has predictive value with respect to their joint-protective potency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Albuterol / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antibodies, Monoclonal / pharmacology
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Chronic Disease
  • Collagen / pharmacology
  • Disease Models, Animal*
  • Immunotherapy
  • Indomethacin / pharmacology*
  • Interleukin-12 / immunology
  • Male
  • Mice
  • Mice, Inbred DBA*
  • Remission Induction
  • Tumor Necrosis Factor-alpha / immunology


  • Adrenergic beta-Agonists
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Collagen
  • Albuterol
  • Indomethacin