Estriol ameliorates autoimmune demyelinating disease - Implications for multiple sclerosis

Objective: To evaluate the use of estriol in the treatment of experimental autoimmune encephalomyelitis (EAE) and other cell mediated autoimmune disea ses. Background: Experimental autoimmune encephalomyelitis is a T helper 1 (Th1)-mediated autoimmune demyelinating disease that is a useful model for the study of immune responses in MS. Interestingly, both EAE and MS have be en shown to be ameliorated during late pregnancy. Methods: Estriol, progest erone, and placebo pellets were implanted in mice during the effector phase of adoptive EAE. Disease scores were compared between treatment groups, an d autoantigen-specific humoral and cellular responses were examined. Result s: Estriol treatment reduced the severity of EAE significantly compared wit h placebo treatment whereas progesterone treatment had no effect. Estriol d oses that induced serum estriol levels that approximated estriol levels dur ing late pregnancy: were capable of ameliorating disease. Estriol-treated E AE mice had significantly higher levels of serum antibodies of the immunogl obulin (Ig) GI isotype specific for the autoantigen myelin basic protein (M BP). Further, MBP-specific T-lymphocyte responses from estriol-treated EAE mice were characterized by significantly increased production of the Th2 cy tokine interleukin 10 (IL-10). T lymphocytes were shown to be the primary s ource of IL-10 within antigen-stimulated splenocyte populations. Conclusion s: Estriol as a hormone involved in immune changes during pregnancy may pro vide a basis for the novel therapeutic use of estriol for MS and other puta tiive Th1-mediated autoimmune diseases that improve during late pregnancy.