Chronic relapsing homologous collagen-induced arthritis in DBA/1 mice as a model for testing disease-modifying and remission-inducing therapies
✍ Scribed by Anne-Marie Malfait; Richard O. Williams; Angela Sara Malik; Ravinder N. Maini; Marc Feldmann
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 868 KB
- Volume
- 44
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
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.