Suppression of type II collagen-induced arthritis by the endogenous estrogen metabolite 2-methoxyestradiol

Arthritis Rheum. 1997 Jan;40(1):154-63. doi: 10.1002/art.1780400120.


Objective: To evaluate the antiarthritic properties of 2-methoxyestradiol, an endogenous metabolite of estradiol, on type II collagen-induced arthritis (CIA) in DBA/1 mice.

Methods: The effects of treatment with 2-methoxyestradiol on the development of CIA were evaluated clinically and histologically. The in vitro effects of 2-methoxyestradiol on lymphocyte and endothelial cell proliferation and differentiation were analyzed by standard methods.

Results: The development of CIA was significantly suppressed by 2-methoxyestradiol. Incubation with 2-methoxyestradiol suppressed the in vitro proliferation of endothelial cells, indicating that this compound down-regulates angiogenesis. Endothelial cell production of nitric oxide (NO) was also down-regulated by 2-methoxyestradiol. In contrast to estradiol, 2-methoxyestradiol exerted neither detectable feminizing effects on the sex organs nor inhibition of leukocyte development in hematopoietic organs.

Conclusion: The development of CIA is suppressed by 2-methoxyestradiol, possibly via inhibition of angiogenesis. Diminished NO production could be of importance in vivo because it is a potent proinflammatory mediator. Since 2-methoxyestradiol exerts only mild side effects compared with estradiol, it is an interesting candidate for therapeutic use in inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Methoxyestradiol
  • Animals
  • Arthritis, Experimental / drug therapy*
  • Body Weight / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • Collagen
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Female
  • Gonads / drug effects
  • Inflammation / drug therapy
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Intercellular Adhesion Molecule-1 / drug effects
  • Joints / drug effects*
  • Joints / pathology
  • Leukocytes / drug effects
  • Male
  • Mice
  • Mice, Inbred DBA
  • Nitric Oxide / metabolism


  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • Estradiol
  • 2-Methoxyestradiol
  • Collagen