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.

The Journal of Rheumatology
|September 12, 2001
PubMed
Abstract

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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