Suppression of Acute Experimental Allergic Encephalomyelitis by the Synthetic Sex Hormone 17-Alpha-Ethinylestradiol: An Immunological Study in the Lewis Rat

Abstract

Induction of experimental allergic encephalomyelitis (EAE) in female Lewis rats led to the well-known clinical symptoms and histological signs. Treatment with the synthetic estrogen 17-α-ethinylestradiol (EE) from day ––4 before induction until day 21 after induction resulted in partial suppression of these signs and symptoms. Analysis of the peripheral blood leukocyte (sub)populations in these treated animals indicated some remarkable changes. However, these changes were also observed without EE treatment. EE treatment of EAE rats resulted in a significant decrease of the relative weights of both thymus and spleen, which changes however were not reflected in the peripheral blood. Apparently the effects of EE treatment on EAE in the present experiments indicate an action locally at the site of the EAE lesion and do not seem to be mediated by gross changes in the levels of peripheral blood leukocytes.

Estrogen Treatment Down-Regulates TNF-α Production and Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Cytokine Knockout Mice

“…Our study differs from previously published studies that reported treatment with estrogen at levels equivalent to or exceeding pregnancy levels suppress the development of EAE (24,25,30), and that the primary mechanisms by which this occurs is through immune deviation toward Th2 cytokines (15,37,38). It is quite possible that the dose and form of estrogen has a critical role in determining the mechanisms of disease inhibition.…”

“…Pregnancy has been shown to suppress the development of EAE (22,23), and estrogen administered at levels equal to or greater than those in pregnancy have been shown to diminish clinical disease (24,25). In recent studies from our laboratory, ovariectomy and loss of endogenous estrogen enhanced the severity of EAE, whereas treatment of mice with estrous and diestrous levels of exogenous estrogen effectively suppressed EAE (26,27).…”

Oral Feeding with Ethinyl Estradiol Suppresses and Treats Experimental Autoimmune Encephalomyelitis in SJL Mice and Inhibits the Recruitment of Inflammatory Cells into the Central Nervous System

“…In this study we demonstrate that EE, an orally active estrogen compound found in oral contraceptives, protects against the development of EAE when administered at the time of disease induction, similar to E2. This oral suppression protocol was even more effective than daily s.c. injections of EE given to Lewis rats during disease induction, as reported by Trooster et al (20). A previous study by Kim et al (16) demonstrated that estriol, given as a pellet after the onset of clinical signs, could reduce the severity of EAE in mice.…”

“…However, structural differences preclude detection of EE using Abs to E2. Earlier studies involving s.c. treatment with EE in rats demonstrated partial suppression of EAE (20,21). However, no significant differences in blood leukocyte populations were found between treated and untreated animals (20).…”

“…Earlier studies involving s.c. treatment with EE in rats demonstrated partial suppression of EAE (20,21). However, no significant differences in blood leukocyte populations were found between treated and untreated animals (20). The purpose of the current study was to test the inhibitory activity of EE as a noninjectable, orally active treatment for EAE.…”