Sex hormones mediate interleukin-1 beta production by human osteoblastic HOBIT cells.

The mechanisms by which the sex hormones achieve their bone-sparing effects remains unresolved. Interleukin-1 beta (IL-1 beta) is an autocrine/paracrine regulator of bone that may be produced in an estrogen-sensitive manner. The regulation of IL-1 beta production by the gonadal steroids was tested in the human osteoblastic HOBIT cell model. Dose-dependent 4-8-fold increases (P < 0.05) in IL-1 beta mRNA levels followed a 6-48 h treatment with 17 beta-estradiol or testosterone. Receptor mediation of these responses was indicated by experiments using 17 alpha-estradiol or flutamide. Tumor necrosis factor-alpha (TNF) dependent increase IL-1 beta mRNA levels were additive to the effects of the steroids. Testosterone and TNF increased IL-1 beta protein release (P < 0.05) while 17 beta-estradiol had little effect on release. The bone-sparing effects of the gonadal steroids may be accomplished, in part, through their mediation of local IL-1 beta production.