Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Glatiramer Acetate (GA), the Immunomodulatory Drug, Inhibits Inflammatory Mediators and Collagen Degradation in OA Cartilage
Attur, Mukundan, Dave, Mandar, Al-Mussawir, Hayf, Patel, Jyoti, Palmer, Glyn, Abramson, Steven B.
Glatiramer acetate, the generic name for Copaxone, an immunomodulatory agent used in the treatment of multiple sclerosis, has been to shown induce interleukin-1 receptor antagonist (IL-1Ra) production in macrophages and microglial cells. In osteoarthritis, the production of inflammatory mediators, particularly IL-1, by chondrocytes may be important in the pathogenesis and progression of OA. We therefore tested the effects of glatiramer acetate or co-polymer on the catabolic activities of chondrocytes in OA cartilage explants cultures.
Human OA cartilage samples and chondrocytes were isolated from patients undergoing knee replacement surgery as approved by IRB. IL-6, IL-8, proMMP-13 and active MMP-13 ELISA were performed as per manufacturer's recommendations (R&D Systems).
We have previously shown that OA cartilage explant cultures spontaneously release inflammatory mediators such as nitric oxide, Prostaglandin E2 (PGE2), interleukins including IL-1beta, IL-6, IL-8 and matrix metalloproteinase (MMPs). Addition of GA (1mg/ml) inhibited 1) IL-6 (25.19 + 13.27 to 15 + 8.5 ng/ml;p<0.05) and IL-8 (30.5 + 9.2 to 15.1 + 6.1 ng/ml;p<0.01) production; 2) inhibited spontaneous proMMP-13 production (35.6+ 14 to 18.5 + 5.1ng/ml;p<0.01); 3) inhibited MMP-13 activity by more than 3050% (p<0.01); 4) inhibited collagen degradation as assayed by CTX II ELISA (7.4 + 1.7 to 4.5 + 1.9 ng/ml; p<0.05). GA also increased significantly (p<0.001) IL-1Ra production by OA cartilage explant ex vivo cultures.
Glatiramer acetate is a complex heterogeneous mixture of polypeptides that exhibits "chondroprotective" properties in OA cartilage, inhibiting the production of cytokine/chemokines production as well as MMP-13 expression/activation. The data suggest that these effects may be due to upregulation of IL-1Ra. Based on these studies, we propose that glatiramer acetate may have potential for disease modifying properties in OA and should be evaluated in vivo animal studies.
To cite this abstract, please use the following information:
Attur, Mukundan, Dave, Mandar, Al-Mussawir, Hayf, Patel, Jyoti, Palmer, Glyn, Abramson, Steven B.; Glatiramer Acetate (GA), the Immunomodulatory Drug, Inhibits Inflammatory Mediators and Collagen Degradation in OA Cartilage [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1347