Effects of leflunomide on human cartilage.
Modern therapeutic approach in rheumatoid arthritis (RA) includes early use of disease-modifying anti-rheumatic drugs (DMARDs). DMARDs may influence the course of disease progression, and their introduction in early RA is recommended to limit irreversible joint damage. Among DMARDs, leflunomide and methotrexate are more utilised in pharmacological therapy. In the present work, we considered the effects of leflunomide, in comparison with those of methotrexate and to those of leflunomide-methotrexate combination on human cartilage to verify its effectiveness in arthritic disease, simulated by our experimental model. We measured in vitro the amount of glycosaminoglycans (GAGs) and the production of nitric oxide (NO) released into the culture medium of human articular cartilage treated with interleukin-1beta (IL-1beta), which promotes the cartilage destruction during articular disease. Leflunomide, in the presence of IL-1beta decreased NO production and GAGs release respect IL-1beta alone treated samples, in dose-related manner. Our results suggest that leflunomide is able to protect cartilage matrix from degradative factors induced by IL-1beta with respect to methotrexate and leflunomide-methotrexate combination.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D004347:Drug Interactions; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology*; D007717:Knee; D000077339:Leflunomide; D008727:Methotrexate / Q000627:therapeutic use; D009569:Nitric Oxide / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D007375:Interleukin-1; D007555:Isoxazoles; D009569:Nitric Oxide; D000077339:Leflunomide; D008727:Methotrexate