Pro-apoptotic effect of nonsteroidal anti-inflammatory drugs on synovial fibroblasts

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the articular synovial tissues. Although the etiology of RA has not yet been elucidated, physical and biochemical inhibition of synovial hyperplasia, which is the origin of articular destruction, may be an effective treatment for RA. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of RA. The mechanism of action of NSAIDs generally involves the inhibition of cyclooxygenase (COX) at sites of inflammation. Thus, NSAIDs were not generally considered to have a so-called anti-rheumatic effect, including inhibition of progressive joint destruction and induction of remission. However, certain conventional NSAIDs and celecoxib, a selective COX-2 inhibitor, have been reported to inhibit synovial hyperplasia by inducing the apoptosis of human synovial fibroblasts. Therefore, it has been suggested that such NSAIDs may not only have an anti-inflammatory effect but also an anti-rheumatic effect. In this review, we summarize findings about the pro-apoptotic effect, in other words, anti-proliferative effect of NSAIDs on synovial fibroblasts from patients with RA.