TY - JOUR T1 - Treatment of collagen induced arthritis by proteolytic enzymes: immunomodulatory and disease modifying effects. JF - The Journal of Rheumatology JO - J Rheumatol SP - 2049 LP - 2059 VL - 28 IS - 9 AU - S R Chintalacharuvu AU - N Urankar-Nagy AU - C A Petersilge AU - F W Abdul-Karim AU - S N Emancipator Y1 - 2001/09/01 UR - http://www.jrheum.org/content/28/9/2049.abstract N2 - 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. ER -