LEFLUNOMIDE INHIBITS CYTOKINE-INDUCED DNA-SYNTHESIS OF RABBIT SYNOVIAL-CELLS IN CULTURE

The effects of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tum or necrosis factor-alpha (TNFalpha) and granulocyte-macrophage colony- stimulating factor (GM-CSF) on DNA synthesis of rabbit synovial cells were studied. IL-1beta 1000-10 000 U . ml-1, IL-6 10-1000 U . ml-1, TN Falpha 0.5 - 50 U . ml-1 and GM-CSF 1 - 100 ng . ml-1 concentration-de pendently stimulated DNA synthesis in rabbit synovial cells in culture . Leflunomide (LFM) and its metabolite A77 1726 elicited an inhibitory effect on such cytokine-induced DNA synthesis of synovial cells. Thes e results suggested that IL-1beta, IL-6, TNFalpha and GM-CSF play a ke y role in the pathogenesis of rheumatoid arthritis. Inhibition of cyto kine-induced proliferation of synovial cells by LFM may partially expl ain its antirheumatic activity.