Treatment of collagen induced arthritis by proteolytic enzymes: immunomodulatory and disease modifying effects
S R Chintalacharuvu1, N Urankar-Nagy, C A Petersilge
1Institute of Pathology, Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
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.
Insights
Protease therapy shows anti-inflammatory effects in early rheumatoid arthritis, similar to ibuprofen. Unlike ibuprofen, proteases preserve cartilage and correct IgG glycosylation, potentially offering better long-term protection against joint destruction.
Area of Science:
- Immunology
- Pharmacology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction.
- Current treatments like ibuprofen offer symptomatic relief but do not fully address underlying disease mechanisms.
- Understanding arthritogenesis is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of a novel protease therapy in a collagen-induced arthritis mouse model.
- To investigate the immunomodulatory mechanisms of protease therapy in arthritis.
- To compare protease therapy with ibuprofen in terms of anti-inflammatory and cartilage-protective effects.
Main Methods:
- Progressive arthritis was induced in DBA/1 mice using Type II collagen immunization.
- Mice were treated with oral proteases, ibuprofen, or left untreated.
- Joints were assessed for clinical, radiographic, and histological changes.
- Serum IgG anti-collagen II levels, IgG glycosylation, and cytokine production were measured.
Main Results:
- Protease and ibuprofen treatments similarly reduced joint inflammation and enhanced Th2 cytokine (interleukin 5) production.
- Protease therapy uniquely protected articular cartilage and normalized IgG glycosylation.
- Protease treatment restored Th1 (interferon-gamma) synthesis, unlike ibuprofen.
Conclusions:
- Protease therapy demonstrates anti-inflammatory efficacy in early collagen-induced arthritis, comparable to ibuprofen.
- Proteases exhibit immunomodulatory effects, including correction of aberrant IgG glycosylation, not observed with ibuprofen.
- These unique effects suggest proteases may offer superior protection against erosive arthritis and could be beneficial for human RA.
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