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Treatment of collagen-induced arthritis by proteolytic enzymes. Immunomodulatory and disease-modifying effects

Chintalacharuvu S. R., Nagy N.U., Petersilge Ch. A., Abdul-Karim F. W., and Emancipator S.N.

From the Institute of Pathology and the Department of Radiology, Case Western Reserve University, Cleveland, OH USA

The Journal of Rheumatology 2001, Vol. 28, No. 9, pp 2049-2059

573 KA

Abstract

Objective

To investigate the efficacy of a novel therapy (proteases) in an animal model of rheumatoid arthritis, and to gain insight to 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 a commercial cocktail of proteases, or left untreated. After two weeks, joints were scored for clinical, radiographic and histologic changes. In addition, 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 were measured.

Results

Amelioration of joint inflammation and destruction, and accentuation of a prototypical Th2 cytokine (IL-5) were similar in ibuprofen and protease treatment groups. However, protease treatment protects and preserves articular cartilage, normalizes the sialylation of IgG and anti-collagen autoantibody and fully restores Th1 (IFN-g) synthesis. Conclusion. Protease therapy has anti-inflammatory efficacy in collagen-induced arthritis, similar to ibuprofen. In addition, 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 patients.