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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.

Original publication

DOI

10.1002/1529-0131(200105)44:5<1215::aid-anr206>3.0.co;2-#

Type

Journal article

Journal

Arthritis and rheumatism

Publication Date

05/2001

Volume

44

Pages

1215 - 1224

Addresses

Kennedy Institute of Rheumatology, Imperial College School of Medicine, London, UK.

Keywords

Animals, Mice, Inbred DBA, Mice, Arthritis, Rheumatoid, Disease Models, Animal, Chronic Disease, Albuterol, Indomethacin, Collagen, Tumor Necrosis Factor-alpha, Adrenergic beta-Agonists, Anti-Inflammatory Agents, Non-Steroidal, Interleukin-12, Antibodies, Monoclonal, Immunotherapy, Remission Induction, Male