EFFECT OF 1,25-DIHYDROXYVITAMIN-D3 ON INTERLEUKIN-1-BETA ACTIONS AND CELL-GROWTH IN HUMAN SYNOVIAL FIBROBLAST-CULTURES

Objective. To investigate the effects of vitamin D3 [1,25-(OH)2D3] met abolites on interleukin 1beta (IL-1beta) stimulated secretory activiti es and on the proliferation of human synovial fibroblasts in culture. Methods. Dose dependent effects on IL-1beta actions were determined in nonproliferating cultures containing 1% fetal calf serum (FCS) in the culture medium. Production of prostaglandin E (PGE), collagenase and hyaluronic acid (HA) was measured respectively by radioimmunoassay, en zymatic degradation of radiolabelled collagen gels after collagenase a ctivation and C-14-glucosamine incorporation. Effects on cell growth i n 10% FCS were monitored colorimetrically, by staining cells with crys tal violet. Results. 1,25-(OH)2D3 inhibited the effects of IL-1beta on PGE production by up to 90%, with half maximal inhibition at 2.0 x 10 (-10) M. Inhibitory effects on stimulated collagenase and HA productio n and cell growth were also found but were less marked. At 10(-7) M 1, 25-(OH)2D3 inhibition was 50, 21 and 50%, respectively. 24,25-dihydrox yvitamin D3 was a less potent inhibitor than 1,25-(OH)2D3. Neither met abolite influenced IL-1beta effects on PGE or sulfated glycosaminoglyc an production in human articular cartilage in tissue culture. Conclusi on. Our results suggest that the active metabolites of vitamin D3 may modulate the behavior of synovial fibroblasts in articular inflammator y processes.