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Chronic relapsing homologous collagen‐induced arthritis in DBA/1 mice as a model for testing disease‐modifying and remission‐inducing therapies
Authors:Anne‐Marie Malfait  Richard O Williams  Angela Sara Malik  Ravinder N Maini  Marc Feldmann
Abstract:

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 anti–interleukin‐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.
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