Estrogen inhibits lipopolysaccharide-induced tumor necrosis factor-alpha release from murine macrophages

Methods Find Exp Clin Pharmacol. 2001 May;23(4):169-73. doi: 10.1358/mf.2001.23.4.634640.


During their reproductive years, female have a lower risk for atherosclerosis as compared with age-matched males, although the mechanisms behind this are not clearly understood. Cytokines, including TNF-alpha play an important role in the pathogenesis of atherosclerosis. We therefore evaluated whether or not there was any difference between 17 beta-estradiol and testosterone in modulating TNF-alpha release from murine bone marrow-derived macrophages (BMM) in vitro. Cells were incubated with or without physiological concentrations (10(-10)-10(-8) M) of 17 beta-estradiol or testosterone for 48 h, followed by an additional 6 h in the absence or presence of lipopolysaccharide (LPS; 10 micrograms/ml). The amount of TNF-alpha released into the culture medium was determined with radioimmunoassay. We found that 17 beta-estradiol or testosterone alone did not affect TNF-alpha release from BMM as compared to untreated controls. Preincubation with 17 beta-estradiol significantly inhibited LPS-induced TNF-alpha release by 18.15% (p < 0.05). 25.28% (p < 0.05) and 40.83% (p < 0.01) for 10(-10), 10(-9) and 10(-8) M of 17 beta-estradiol, respectively, as compared to LPS alone. In contrast, testosterone tested for 3 concentrations did not significantly effect TNF-alpha release induced by LPS. The results indicate that 17 beta-estradiol, but not testosterone, inhibits TNF-alpha release from LPS-stimulated macrophages, which may be one of the mechanisms by which estrogen protects against atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cells, Cultured
  • Estradiol / pharmacology*
  • Female
  • Lipopolysaccharides / administration & dosage*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Mice
  • Testosterone / pharmacology*
  • Tumor Necrosis Factor-alpha / drug effects*
  • Tumor Necrosis Factor-alpha / metabolism


  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Testosterone
  • Estradiol