17β-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: A potential mechanism for the antiosteoporotic effect of estrogens

Giuseppe Girasole, Robert L. Jilka, Giovanni Passeri, Scott Boswell, George Boder, Daniel C. Williams, Stavros C. Manolagas

Research output: Contribution to journalArticle

575 Scopus citations

Abstract

The effect of 17β-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 α (TNFα). Addition of 17β-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 17α-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17β-estradiol. 17β-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.

Original languageEnglish (US)
Pages (from-to)883-891
Number of pages9
JournalJournal of Clinical Investigation
Volume89
Issue number3
DOIs
StatePublished - Jan 1 1992

Keywords

  • Interleukin-1
  • Marrow stroma
  • Osteoclast
  • Osteoporosis
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Medicine(all)

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