IL-1-BETA AND IL-6 STIMULATE THE PRODUCTION OF PLATELET-ACTIVATING-FACTOR (PAF) BY CULTURED RABBIT SYNOVIAL-CELLS

The aim of this study was to determine whether synovial cells are capa ble of producing PAF in the presence of cytokines such as IL-1 beta an d IL-6 and other stimuli. Synovial cells were obtained from joints of healthy rabbits. PAF production was assayed by measurement of serotoni n release in rabbit platelets and the incorporation of H-3-acetate int o PAF. Synovial cells produced PAF after 5 min of incubation with iono phore A23187, reaching the maximal amount at 15 min (4.3 +/- 0.7 x 10( -3) pmol of PAF/mg protein, P < 0.005, n = 4), and declining afterward s. The treatment of synoviocytes with IL-1 beta and IL-6 induced synth esis of PAF after 5 min of stimulation, reaching the greatest producti on at 15 min with IL-6 and 30 min with IL-1 beta(3.6 +/- 1.1 x 10(-3) and 3.3 +/- 1.2 pmol of PAF/mg protein, respectively, P < 0.05, n = 4) . The incubation of the cells with PMSF an inhibitor of acetylhydrolas e, before the addition of the stimuli, increased the incorporation rat e of 3H-acetate, suggesting a rapid degradation of PAF by synoviocytes . These results demonstrate that synovial cells can produce PAF after stimulation with agonists, such as ionophore, and cytokines. Thus, PAF , acting alone or with other mediators, could amplify the inflammatory joint reaction.