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.
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.
Girasole
G
G
Section of Endocrinology and Metabolism, Veteran's Administration Medical Center, Indianapolis, Indiana 46202.
Jilka
R L
RL
Passeri
G
G
Boswell
S
S
Boder
G
G
Williams
D C
DC
Manolagas
S C
SC
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
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D002116:Calcitonin