E. Josefsson et A. Tarkowski, SUPPRESSION OF TYPE-II COLLAGEN-INDUCED ARTHRITIS BY THE ENDOGENOUS ESTROGEN METABOLITE 2-METHOXYESTRADIOL, Arthritis and rheumatism, 40(1), 1997, pp. 154-163
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.