Small molecules regulating apoptosis in the synovium in rheumatoid arthritis.

OBJECTIVES: To study the rate of apoptosis and expression of pro- and anti-apoptotic molecules in the synovial membrane in early and late rheumatoid arthritis (RA). METHODS: Samples of the synovium, cartilage, synovial fluid, and blood serum were obtained from patients with seropositive RA. The localization of Bcl-2-, p53- and TUNEL-immunoreactive cells in the synovial membrane was studied. The level of the soluble Fas (sFas) receptor was determined in the blood serum and synovial fluid using an immunoassay. RESULTS: In early RA, p53-immunoreactive synovial cells of type A were found to form rare aggregates in the intima. In late RA, on the contrary, these cells increased in number and occurred predominantly in the synovial stroma. Bcl-2-immunoreactive synovial cells were observed in lymphocytic infiltrates in the intima. They were found mainly in early RA. In late RA, their number decreased. The apoptotic index determined from the proportion of TUNEL-reactive synovial cell nuclei reached a maximum in late RA. The temporal differences in the rate of apoptosis were correlated with the humoral level of sFas, which increased significantly in late RA. On the contrary, in the synovial fluid, the sFas level decreased monotonically from early to late RA. CONCLUSION: In early RA, in the synovial membrane, the rate of apoptosis and p-53-immunostaining intensity were low, and Bcl-2-immunostaining intensity was high. The sFas level in synovial fluid was high. In late RA, the rate of apoptosis and p-53-immunostaining intensity increased, Bcl-2-immunostaining intensity decreased, as did the sFas level.