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

Abstract

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.