ESTROGEN INHIBITS INTERLEUKIN-6 PRODUCTION AND GENE-EXPRESSION IN A HUMAN OSTEOBLASTIC CELL-LINE WITH HIGH-LEVELS OF ESTROGEN-RECEPTORS

Some studies suggest that estrogen acts on bone by decreasing the prod uction of interleukin-6 (IL-6), a cytokine that increases bone resorpt ion, by osteoblasts or bone marrow cells, However, other studies have not confirmed this, possibly because of a low and variable number of e strogen receptors (ER) in the model systems used, Thus, we employed a recently developed human fetal osteoblast cell Line with high levels o f ER, Treatment (n = 4 experiments) with 0.01 to 10 nM of 17 beta-estr adiol had no effect on the constitutive production of IL-6, However, s timulated production, induced by treatment with IL-1 beta plus tumor n ecrosis factor-alpha (TNF-alpha), was reduced in a dose-dependent mann er to 74 +/- 3% (mean +/- SEM) of control (p < 0.01). This response wa s blocked by cotreatment with the type II antiestrogen ICI 182,780, Tr eatment,vith hydrocortisone (1 mu M), a known inhibitor of IL-6 produc tion in many cell types, reduced IL-6 production to 17 +/- 1% of contr ol (p < 0.001). As assessed by Northern analysis, treatment (n = 3 exp eriments) with 0.01-10 nM of 17 beta-estradiol decreased steady-state levels of IL-6 mRNA in a dose-dependent manner, These data support the hypothesis that at least part of the antiresorptive action of estroge n in humans is mediated by decreased production of IL-6 by osteoblasti c cells.