17-BETA-ESTRADIOL AND 1-ALPHA,25-DIHYDROXYCHOLECALCIFEROL MODULATE CONSTITUTIVE AND BONE MATRIX-INDUCED INTERLEUKIN-1-BETA (IL-1-BETA) PRODUCTION BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS ISOLATED FROM POSTMENOPAUSAL WOMEN

Local production and release of interleukin-1 (IL-1) may be of importa nce for bone remodelling, since this cytokine is known to stimulate bo ne resorption. We have studied the effect of bone matrix constituents on IL-1 beta production by peripheral blood mononuclear cells (PBMCs) isolated from 20 postmenopausal non-osteoporotic women. Hydroxyapatite (0.5 mg/ml) and heat-denaturated collagen (25 mu g/ml) stimulated IL- 1 beta production 5-fold and 520-fold, respectively, compared to contr ol (p<0.01). In contrast, transforming growth factor-beta (TGF-beta, 1 0 ng/ml), a cytokine which is abundant in bone matrix, suppressed medi an IL-1 beta release to 13% of control value (p<0.01). The bone matrix -induced changes in IL-1 beta production were modulated by 10 nmol/l 1 7 beta-oestradiol and 10 nmol/l 1 alpha,25-dihydroxy-cholecalciferol ( 1,25(OH)(2)D3). Specifically, 17 beta-oestradiol stimulated constituti ve IL-1 beta release with 89% (p<0.01) and nullified the suppressive e ffect of TGF-beta. Moreover, 1,25(OH)(2)D3 had a synergistically stimu latory effect with both hydroxyapatite and collagen, although there wa s no effect of this hormone when added alone. The adherent cells were slightly more elongated after treatment with 1,25(OH)(2)D3 and collage n, while TGF-beta and 17 beta-oestradiol had no effect on cellular mor phology. Addition of hydroxyapatite resulted in long and spindle-shape d cells, and phagocytosis of the particles occurred. The modulatory ef fects of oestrogen and vitamin D on constitutive and bone-matrix induc ed IL-1 beta production by PBMCs may be of importance for bone remodel ling during postmenopausal bone loss and at a site of fracture.