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The Journal of Immunology, 2003, 171: 6267-6274.
Copyright © 2003 by The American Association of Immunologists

Immune Modulation in Multiple Sclerosis Patients Treated with the Pregnancy Hormone Estriol 1

Samantha S. Soldan, Ana Isabel Alvarez Retuerto, Nancy L. Sicotte and Rhonda R. Voskuhl2

Department of Neurology, Reed Neurological Research Center, University of California School of Medicine, Los Angeles, CA 90095

The protective effect of pregnancy on putative Th1-mediated autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis, is associated with a Th1 to Th2 immune shift during pregnancy. The hormone estriol increases during pregnancy and has been shown to ameliorate experimental autoimmune encephalomyelitis and collagen-induced arthritis. In addition, estrogens induce cytokine changes consistent with a Th1 to Th2 shift when administered in vitro to human immune cells and in vivo to mice. In a pilot trial, oral estriol treatment of relapsing remitting multiple sclerosis patients caused significant decreases in enhancing lesions on brain magnetic resonance imaging. Here, the immunomodulatory effects of oral estriol therapy were assessed. PBMCs collected longitudinally during the trial were stimulated with mitogens, recall Ags, and glatiramer acetate. Cytokine profiles of stimulated PBMCs were determined by intracellular cytokine staining (IL-5, IL-10, IL-12 p40, TNF-{alpha}, and IFN-{gamma}) and cytometric bead array (IL-2, IL-4, IL-5, IL-10, TNF-{alpha}, and IFN-{gamma}). Significantly increased levels of IL-5 and IL-10 and decreased TNF-{alpha} were observed in stimulated PBMC isolated during estriol treatment. These changes in cytokines correlated with reductions of enhancing lesions on magnetic resonance imaging in relapsing remitting multiple sclerosis. The increase in IL-5 was primarily due to an increase in CD4+ and CD8+ T cells, the increase in IL-10 was primarily due to an increase in CD64+ monocytes/macrophages with some effect in T cells, while the decrease in TNF-{alpha} was primarily due to a decrease in CD8+ T cells. Further study of oral estriol therapy is warranted in Th1-mediated autoimmune diseases with known improvement during pregnancy.




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