SUPPRESSION OF TYPE-II COLLAGEN-INDUCED ARTHRITIS BY THE ENDOGENOUS ESTROGEN METABOLITE 2-METHOXYESTRADIOL

Objective. To evaluate the antiarthritic properties of 2-methoxyestrad iol, an endogenous metabolite of estradiol, on type II collagen-induce d arthritis (CIA) in DBA/1 mice. Methods. The effects of treatment wit h 2-methoxyestradiol on the development of CIA were evaluated clinical ly and histologically. The in vitro effects of 2-methoxyestradiol on l ymphocyte and endothelial cell proliferation and differentiation were analyzed by standard methods. Results. The development of CIA was sign ificantly suppressed by 2-methoxyestradiol. Incubation with 2-methoxye stradiol suppressed the in vitro proliferation of endothelial cells, i ndicating that this compound down-regulates angiogenesis. Endothelial cell production of nitric oxide (NO) was also down-regulated by 2-meth oxyestradiol. In contrast to estradiol, 2-methoxyestradiol exerted nei ther detectable feminizing effects on the sex organs nor inhibition of leukocyte development in hematopoietic organs. Conclusion. The develo pment of CIA is suppressed by 2-methoxyestradiol, possibly via inhibit ion of angiogenesis. Diminished NO production could be of importance i n vivo because it is a potent proinflammatory mediator. Since 2-methox yestradiol exerts only mild side effects compared with estradiol, it i s an interesting candidate for therapeutic use in inflammatory disease s.