Ethinyl estradiol treats collagen-induced arthritis in DBA/1LacJ mice by inhibiting the production of TNF-alpha and IL-1beta.
We previously demonstrated the therapeutic effects of ethinyl estradiol (EE), an orally active estrogen and a component of birth control pills, in encephalitogenic autoimmune encephalomyelitis (EAE). In this study, we report the effectiveness of EE in treating collagen-induced arthritis (CIA) induced with bovine type II collagen (bCII) in DBA/1LacJ mice, a CIA susceptible strain. Both low and high doses of EE notably suppressed clinical and histological signs of CIA in a dose-dependent manner compared to vehicle-treated controls. Oral treatment with EE decreased proliferation and secretion of pro-inflammatory factors, TNF-alpha IFN-gamma, MCP-1 and IL-6 by bCII peptide-specific T cells, production of bCII-specific IgG2a antibodies, and mRNA for cytokines, chemokines and chemokine receptors in joint tissue. This is the first report demonstrating effective treatment of joint inflammation and clinical signs of CIA with orally administered ethinyl estradiol, thus supporting its possible clinical use for treating rheumatoid arthritis in humans.
Subramanian
Sandhya
S
Neuroimmunology Research R&D-31, Portland Veterans Affairs Medical Center, 3710 SE U.S. Veterans Hospital Road, Portland, OR 97239, USA.
Tovey
Micah
M
Afentoulis
Michael
M
Krogstad
Aric
A
Vandenbark
Arthur A
AA
Offner
Halina
H
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D024043:Collagen Type II; D016207:Cytokines / Q000378:metabolism; D004967:Estrogens / Q000627:therapeutic use*; D004997:Ethinyl Estradiol / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D024043:Collagen Type II; D016207:Cytokines; D004967:Estrogens; D007074:Immunoglobulin G; D012333:RNA, Messenger; D004997:Ethinyl Estradiol