Effects of Aceclofenac and Diclofenac on Synovial Inflammatory Factors in Human Osteoarthritis

Summary

Osteoarthritis is a degenerative disease of the articular cartilage associated with synovial inflammation. Hyperplasia of synovial cells and infiltrating macrophages increase local synthesis of prostaglandins (mainly PGE₂) and cytokines. Excess synthesis of PGE₂ by osteoarthritic chondrocytes is also among the factors contributing to the degradation of the cartilage matrix. We evaluated the effect of a new NSAID, aceclofenac, at therapeutic concentrations (2, 4 and 8 mg/L) on the level of PGE₂ in osteoarthritic synovial membrane and cartilage and on the levels of interleukin-1β (IL-1β) and tumour necrosis factor alpha (TNF-α) in osteoarthritic synovial membranes following lipopolysaccharide (LPS) [20 mg/L] treatment, and compared it with diclofenac (125 and 250 µg/L). Results showed that aceclofenac and diclofenac almost completely abrogated the PGE₂ synthesis at all concentrations tested on osteoarthritic synovial membranes and cartilages. Moreover, both NSAIDs demonstrated a statistically significant inhibition of LPS-stimulated IL-1β and TNF-α synthesis.

The destruction of articular joint tissue is a key element in the osteoarthritic process. Upregulation of catabolic factors contribute to this degradation. Investigation of drugs that are able to reduce the synthesis of some of these factors is of the utmost importance. We reported that NSAIDs, such as aceclofenac and diclofenac, can significantly decrease the synthesis of three major factors, PGE₂, IL-1β and TNF-α, in joint articular tissues.