title: 17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens.
abstract: The effect of 17 beta-estradiol on interleukin-6 (IL-6) synthesis was examined in murine bone marrow-derived stromal cell lines, normal human bone-derived cells, and nontransformed osteoblast cell lines from mice and rats. In all these cell types IL-6 production was stimulated as much as 10,000-fold in response to the combination of recombinant interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). Addition of 17 beta-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. Testosterone and progesterone (but not 17 alpha-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17 beta-estradiol. 17 beta-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria. The TNF-stimulated osteoclast development was also suppressed by a neutralizing monoclonal anti-IL-6 antibody. This in vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.
authors.affiliation: Section of Endocrinology and Metabolism, Veteran's Administration Medical Center, Indianapolis, Indiana 46202.
authors.forename: G
authors.initials: G
authors.lastname: Girasole
authors.forename: R L
authors.initials: RL
authors.lastname: Jilka
authors.forename: G
authors.initials: G
authors.lastname: Passeri
authors.forename: S
authors.initials: S
authors.lastname: Boswell
authors.forename: G
authors.initials: G
authors.lastname: Boder
authors.forename: D C
authors.initials: DC
authors.lastname: Williams
authors.forename: S C
authors.initials: SC
authors.lastname: Manolagas
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells; D002116:Calcitonin / Q000378:metabolism; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D002116:Calcitonin