Late Pregnancy Suppresses Relapses in Experimental Autoimmune Encephalomyelitis: Evidence for a Suppressive Pregancy-Related Serum Factor

Abstract

Women with multiple sclerosis have significantly diminished disease activity during pregnancy. The purpose of our study was to identify the underlying mechanism for the diminished disease activity. We found that during the period of late pregnancy there is protection against paralysis, during both the induction and effector phases of relapsing experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. We did not find any changes in the cytokine secretion profiles or the proliferative activity of autoreactive T cells from mice induced during late pregnancy compared with virgin controls. In mice mated after disease onset, the inflammatory histologic lesions did not clear, despite marked clinical improvement during pregnancy. We found evidence for a serum factor present in late pregnancy that suppresses T cell activation. In the presence of sera taken from mice late in pregnancy, the proliferative response and IL-2 production of proteolipid protein p139–151-specific T cells were significantly diminished as compared with stimulation in the presence of normal mouse sera. In conclusion, serum from late pregnancy has the capacity to down-regulate T cell responses and might be associated with the amelioration of disease activity in experimental autoimmune encephalomyelitis.

Prolactin Is Not Required for the Development of Severe Chronic Experimental Autoimmune Encephalomyelitis

“…Pregnancy also importantly affects the clinical course of MS. Relapse rate significantly declines during the third trimester of pregnancy but considerably increases in the first 3 mo after delivery, if compared with prepregnancy rates (4,5). Similarly to human disease, pregnancy suppresses clinical symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model for MS (6,7), and induction of chronic EAE in the postpartum period results in enhanced mortality and slightly worsened severity (7). Among sexrelated factors, hormones have been hypothesized to play an important role in regulating MS and EAE (3).…”

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

“…Pregnancy and hormones associated with pregnancy exert a protective effect on disease course (12)(13)(14). Pregnant animals showed less severe disease than nonpregnant mice (14,15), and treatment at disease onset with estriol inhibited the severity of passively induced EAE (16).…”

Sex Hormones and Multiple Sclerosis

“…Data about clinical improvement of EAE during pregnancy are also highly consistent [42,[49][50][51][52]. Earlier studies could not find any histopathological differences between virgin and pregnant mice with EAE [49,50], but a succeeding investigation found reduced CNS demyelination and cell infiltration during late pregnancy in animals with preinduced EAE [51]. Later on, an elegant experiment of Haghmorad et al [52] has confirmed that pregnancy-induced alleviation of clinical manifestations is accompanied by reduced CNS demyelination and cell infiltration.…”

“…Numerous studies using rats, rabbits, guinea pigs, and SJL mice have confirmed that pregnancy reduces the incidence of the disease and/or delays the day of onset [46][47][48][49][50]. Data about clinical improvement of EAE during pregnancy are also highly consistent [42,[49][50][51][52].…”

“…Numerous studies using rats, rabbits, guinea pigs, and SJL mice have confirmed that pregnancy reduces the incidence of the disease and/or delays the day of onset [46][47][48][49][50]. Data about clinical improvement of EAE during pregnancy are also highly consistent [42,[49][50][51][52]. Earlier studies could not find any histopathological differences between virgin and pregnant mice with EAE [49,50], but a succeeding investigation found reduced CNS demyelination and cell infiltration during late pregnancy in animals with preinduced EAE [51].…”