Low-Dose Estrogen Therapy Ameliorates Experimental Autoimmune Encephalomyelitis in Two Different Inbred Mouse Strains
Open accessAbstract
It has been proposed that homeostatic levels of estrogen can enhance female susceptibility to autoimmunity, whereas the heightened levels of estrogen associated with pregnancy are protective. This hypothesis was tested using the mouse model of experimental autoimmune encephalomyelitis (EAE). Diestrus (<100 pg/ml in serum) levels of 17β-estradiol were found to significantly reduce the clinical manifestations of active EAE in both male and female mice. Estriol was also effective but at doses below those previously established for pregnancy. The reduction in disease severity was accompanied by a coincident reduction in the number and size of inflammatory foci in the CNS of estrogen (17β-estradiol or estriol)-treated mice. Recipients of encephalitogenic T cells from low-dose estrogen-treated mice developed less severe paralysis than mice receiving T cells from placebo-treated mice. A modest shift in Th1/Th2 balance suggested that low dose estrogen therapy could bias the immune reaction toward a protective anti-inflammatory cytokine response. However, estrogen treatment at the onset of active EAE failed to reduce disease severity, a result that is consistent with the hypothesis that naive cells are more sensitive to sex hormones than differentiated effector cells. These data suggest that treatment with low doses of estrogen can reduce the capacity of developing myelin-reactive T cells to initiate disease and challenges the idea that increased susceptibility to autoimmunity in females is dependent on homeostatic levels of estrogen.
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In EAE, administration of estrogens leads to functional benefits.
“In EAE, administration of estrogens lead to functional benefits 5, 25, 43, 52.”
From SJL Mice Exposed to Cuprizone Intoxication Reveal Strain and Gender Pattern Differences in Demyelination (2009) · cites this paper as [5]
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“17 beta-estradiol (E2) is a form of estrogen that has been shown to reduce symptoms in EAE [75].”
BackgroundSex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders
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- Authors
- Bebo, B. F., Fyfe-Johnson, A., Adlard, K., Beam, A. G., Vandenbark, A. A., & Offner, H.
- Affiliations
- United States Department of Veterans Affairs (US)
- Department of Veterans Affairs, Neuroimmunology Research, Oregon Health Sciences University , Portland, OR 97201
- Corresponding author
- Adlard, Kirsten
- Offner, Halina
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-02-01
- Volume
- 166
- Issue
- 3
- Pages
- 2080-2089
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2157275878
- Cited by
- 341
- References
- 1
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 10 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 12 · 2017: 12 · 2016: 12 · 2015: 15 · 2014: 18 · 2013: 15 · 2012: 18
- FWCI
- 14.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01ai042376-01)
- National Institute of Allergy and Infectious Diseases (AI 42376)
- National Institute of Neurological Disorders and Stroke (NS23444, NS23112, R01NS023444)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- estrogen therapy, estradiol, estriol, experimental autoimmune encephalomyelitis, multiple sclerosis, sex differences in autoimmunity, myelin-specific T cells, Th1/Th2 balance, neuroinflammation, inbred mouse strains
- MeSH terms
- Animals, Dose-Response Relationship, Immunologic, Drug Administration Schedule, Drug Implants, Encephalomyelitis, Autoimmune, Experimental, Estradiol, Estriol, Female, Male, Mice, Inbred C57BL, Mice, Inbred Strains, Paralysis, Severity of Illness Index, Sex Factors, Species Specificity, T-Lymphocytes, Incidence, Adoptive Transfer, Mice
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