TY - JOUR
T1 - Ethinyl estradiol treats collagen-induced arthritis in DBA/1LacJ mice by inhibiting the production of TNF-α and IL-1β
AU - Subramanian, Sandhya
AU - Tovey, Micah
AU - Afentoulis, Michael
AU - Krogstad, Aric
AU - Vandenbark, Arthur A.
AU - Offner, Halina
N1 - Funding Information:
This work was supported by grants AI42376, NS23221, and NS23444 from the National Institutes of Health (NIH) and grants from the National Multiple Sclerosis Society (NMSS), and the Department of Veterans Affairs.
PY - 2005/5
Y1 - 2005/5
N2 - 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-α IFN-γ, 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.
AB - 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-α IFN-γ, 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.
KW - Collagen-induced arthritis
KW - Cytokines
KW - Ethinyl estradiol
KW - Oral therapy
KW - Regulation of T cells and antibodies
UR - http://www.scopus.com/inward/record.url?scp=18844411612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18844411612&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2005.01.006
DO - 10.1016/j.clim.2005.01.006
M3 - Article
C2 - 15885639
AN - SCOPUS:18844411612
SN - 1521-6616
VL - 115
SP - 162
EP - 172
JO - Clinical Immunology
JF - Clinical Immunology
IS - 2
ER -