Suppressive Effect of Pregnancy on the Development of Experimental Allergic Encephalomyelitis in Rabbits

Abstract

In the present study we have investigated the influence of pregnancy on the induction and development of experimental autoimmune encephalomyelitis (EAE) in rabbits in relation to the time of gestation. Randomly bred rabbits were immunized with encephalitogenic bovine brain homogenate in complete Freund's adjuvant before or during pregnancy. The appearance of EAE was delayed and occurred only after delivery, abortion, or fetal resorption. The incidence of the disease was lower and the duration longer. The levels of antibodies to myelin basic protein, an autoantigen of EAE, as measured by solid phase radioimmunoassay, were lower in the pregnant rabbits as compared to the nonpregnant animals. The suppressive influence of pregnancy on the induction and the development of EAE confirms previous reports demonstrating amelioration of autoimmune diseases and other immunological reactions during the second half of human pregnancy. This effect might be partially attributed to the increased level of alpha-fetoprotein (AFP) and/or other pregnancy-associated factors in maternal serum.

Low-Dose Estrogen Therapy Ameliorates Experimental Autoimmune Encephalomyelitis in Two Different Inbred Mouse Strains

“…A number of studies support the hypothesis that the increased female susceptibility to autoimmune disease is largely due to effects mediated by estrogen (34 -36). However, it is well known that pregnancy levels of estrogen are immunosuppressive and protect against a number of experimental autoimmune disorders including collagen-induced arthritis (37,38) and EAE (16,17). To explain this apparent dichotomy, it has been proposed that the response to estrogen is biphasic, with basal levels of hormone leading to conditions favoring autoimmunity and pregnancy levels of hormone associated with protection from autoimmune disease (23).…”

“…Interestingly, sex hormones have been found to alter the disease course in the EAE model system. Pregnancy has been shown to protect animals from EAE (16,17), and estrogen administered at levels equal or greater than those found during pregnancy have been shown to suppress the clinical and histopathological symptoms of EAE in mice and rats (18,19). Recent studies have found that estriol (E3), a hormone produced by the placenta during pregnancy, had profound effects on EAE (20), and, based on these results, human trials using E3 to treat MS patients have begun.…”

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

“…In view of the fact that the enzyme converting testosterone into estradiol, aromatase, is present in several cells and tissues it remains to be shown whether testosterone exerts its anti-inflammatory effect directly or through conversion in the female sex hormone. Gender differences in susceptibility to and severity of EAE have also been known for many years ( [71,162,244]). …”

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

“…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).…”