EFFECTS OF ACECLOFENAC AND DICLOFENAC ON SYNOVIAL INFLAMMATORY FACTORS IN HUMAN OSTEOARTHRITIS

Osteoarthritis is a degenerative disease of the articular cartilage as sociated with synovial inflammation. Hyperplasia of synovial cells and infiltrating macrophages increase local synthesis of prostaglandins ( mainly PGE(2)) and cytokines. Excess synthesis of PGE(2) by osteoarthr itic chondrocytes is also among the factors contributing to the degrad ation of the cartilage matrix. We evaluated the effect of a new NSAID, aceclofenac, at therapeutic concentrations (2, 4 and 8 mg/L) on the l evel of PGE(2) in osteoarthritic synovial membrane and cartilage and o n the levels of interleukin-1 beta (IL-1 beta) and tumour necrosis fac tor alpha (TNF-alpha) in osteoarthritic synovial membranes following l ipopolysaccharide (LPS) [20 mg/L] treatment, and compared it with dicl ofenac (125 and 250 mu g/L). Results showed that aceclofenac and diclo fenac almost completely abrogated the PGE(2) synthesis at all concentr ations tested on osteoarthritic synovial membranes and cartilages. Mor eover, both NSAIDs demonstrated a statistically significant inhibition of LPS-stimulated IL-1 beta and TNF-alpha synthesis. The destruction of articular joint tissue is a key element in the osteoarthritic proce ss. Upregulation of catabolic factors contribute to this degradation. Investigation of drugs that are able to reduce the synthesis of some o f these factors is of the utmost importance. We reported that NSAIDs, such as aceclofenac and diclofenac, can significantly decrease the syn thesis of three major factors, PGE(2), IL-1 beta and TNF-alpha, in joi nt articular tissues.