17 beta-Oestradiol 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 importance for bone remodeling, since this cytokine is known to stimulate bone 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 micrograms/ml) stimulated IL-1 beta production 5-fold and 520-fold, respectively, compared to control (p < 0.01). In contrast, transforming growth factor-beta (TGF-beta, 10 ng/ml), a cytokine which is abundant in bone matrix, suppressed median 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/1 17 beta-oestradiol and 10 nmol/1 1 alpha,25-dihydroxy-cholecalciferol (1,25(OH)2D3). Specifically, 17 beta oestradiol stimulated constitutive IL-1 beta release with 89% (p < 0.01) and nullified the suppressive effect of TGF-beta. Moreover, 1,25(OH)2D3 had a synergistically stimulatory effect with both hydroxyapatite and collagen, although there was no effect of this hormone when added alone. The adherent cells were slightly more elongated after treatment with 1,25(OH)2D3 and collagen, while TGF-beta and 17 beta-oestradiol had no effect on cellular morphology. Addition of hydroxyapatite resulted in long and spindle-shaped cells, and phagocytosis of the particles occurred. The modulatory effects of oestrogen and vitamin D on constitutive and bone-matrix induced IL-1 beta production by PBMCs may be of importance for bone remodelling during postmenopausal bone loss and at a site of fracture.