Treatment with selective estrogen receptor modulators regulates myelin specific T‐cells and suppresses experimental autoimmune encephalomyelitis
- 20 November 2008
- Vol. 57 (7), 777-790
- https://doi.org/10.1002/glia.20805
Abstract
Steroidal estrogens can regulate inflammatory immune responses and may be involved in the suppression of multiple sclerosis (MS) during pregnancy. However, the risks and side effects associated with steroidal estrogens may limit their usefulness for long‐term MS therapy. Selective estrogen receptor modulators (SERMs) could provide an alternative therapeutic strategy, because they behave as estrogen agonists in some tissues, but are either inert or behave like estrogen antagonists in other tissues. In this study, we investigated the ability of two commercially available SERMs (tamoxifen and raloxifene) to regulate myelin specific immunity and experimental autoimmune encephalomyelitis (EAE) in mice. Both tamoxifen and raloxifene suppressed myelin antigen specific T‐cell proliferation. However, tamoxifen was more effective in this regard. Tamoxifen treatment reduced the induction of major histocompatibility complex II by lipopolysaccharide stimulated dendritic cells and decreased their ability to activate myelin specific T‐cells. At lower doses, tamoxifen was found to increase the levels of Th2 transcription factors and induce a Th2 bias in cultures of myelin‐specific splenocytes. EAE symptoms and the degree of demyelination were less severe in mice treated with tamoxifen than in control mice. These findings support the notion that tamoxifen or related SERMs are potential agents that could be used in the treatment of inflammatory autoimmune disorders that affect the central nervous system.Keywords
This publication has 63 references indexed in Scilit:
- Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of treg cells, and enhanced expression of the PD-1 costimulatory pathwayJournal of Neuroscience Research, 2006
- T Lymphocytes Do Not Directly Mediate the Protective Effect of Estrogen on Experimental Autoimmune EncephalomyelitisThe American Journal of Pathology, 2004
- CD44 overexpression by oligodendrocytes: A novel mouse model of inflammation‐independent demyelination and dysmyelinationGlia, 2004
- Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled TrialJama-Journal Of The American Medical Association, 2002
- Estrogen-Mediated Neuroprotection After Experimental Stroke in Male RatsStroke, 1998
- Gender-Linked Brain Injury in Experimental StrokeStroke, 1998
- Estradiol Down‐Regulates LPS‐Induced Cytokine Production and NFkB Activation in Murine MacrophagesAmerican Journal of Reproductive Immunology, 1997
- Animal models of human disease Experimental autoimmune encephalomyelitis in rodents as a model for human demyelinating diseaseClinical Immunology and Immunopathology, 1995
- TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional PropertiesAnnual Review of Immunology, 1989
- Estrogen treatment enhances survival of cultured fetal rat amygdala neurons in a defined mediumDevelopmental Brain Research, 1986