Objective: To investigate the efficacy of a novel therapy (proteases) in an animal model of rheumatoid arthritis, and to investigate the mechanisms of arthritogenesis.
Methods: We induced progressive arthritis in male DBA/1 mice by immunization and boosting with Type II collagen; groups of mice were treated orally twice daily with either ibuprofen or proteases, or were left untreated. After 2 weeks, joints were scored for clinical, radiographic, and histologic changes. In addition, we measured serum levels of IgG anti-collagen II, the glycosylation of circulating total and anti-collagen II IgG, and cytokine production by lymphocytes isolated from lymph nodes.
Results: Amelioration of joint inflammation, and accentuation of a prototypical Th2 cytokine (interleukin 5) were similar in the ibuprofen and protease treatment groups. However, protease treatment protects and preserves articular cartilage, normalizes the sialylation of IgG and anti-collagen antibody, and fully restores Th1 (interferon-gamma) synthesis, distinct from ibuprofen.
Conclusion: Protease therapy has antiinflammatory efficacy in the early (inflammatory) phase of collagen induced arthritis, similar to ibuprofen. The immunomodulatory effects of proteases, not seen with ibuprofen, may underlie a correction of aberrant IgG glycosylation and/or contribute to the increased capacity of protease to delay or forestall erosive and destructive arthritis or ankylosis. Similar effects may apply to spontaneous RA in humans.
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