Apoptosis and p53 expression in rat adjuvant arthritis

RA is a chronic inflammatory disorder that is characterized by inflammation and proliferation of synovial tissue. The disease is still associated with long-term morbidity and early mortality, despite treatment with antirheumatic drugs. Inadequate apoptosis appears to contribute toward prolonged survival and constitutive activation of specialized cells in rheumatoid synovium [ 1 , 2 ]. The amount of DNA fragmentation is significantly increased in rheumatoid synovium [ 3 , 4 ], which is presumably due to the toxic environment of the chronically inflamed joint [ 5 ]. Only low numbers of apoptotic cells are present in rheumatoid synovial tissue, however [ 4 , 6 , 7 , 8 ]. The proportion of cells with DNA strand breaks is so great that this disparity suggests impaired apoptosis. The observation that mice with the lymphoproliferative or generalized lymphoproliferative disorder, which have mutations that inactivate Fas and Fas ligand, respectively, develop pathology similar to that observed in immune-mediated diseases [ 9 , 10 ] illustrates that reduced apoptosis may play an important role in the pathogenesis of synovitis.