Drew Paul D, Chavis Janet A, Bhatt Renu
Department of Anatomy and Neurobiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Ann N Y Acad Sci. 2003 Dec;1007:329-34. doi: 10.1196/annals.1286.031.
Multiple sclerosis (MS) occurs more commonly in females than males. However, the mechanisms resulting in gender differences in MS are unknown. Several studies have suggested that sex steroids influence the development and severity of MS. For example, pregnancy influences MS symptoms, with remission in the third trimester of gestation, followed by exacerbation in the postpartum period. In addition, oral contraceptives containing female sex steroids have been associated with a lower risk of developing MS and decreased disability. Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disorder initiated by T cells reactive against central nervous system (CNS) antigens. EAE is characterized by inflammation and demyelination of the CNS, and by remittent paralysis-features consistent with MS. Recent studies have suggested that female sex steroids may modulate EAE, at least in part, through effects on T cells. For example, sex steroids shift T cells toward a Th2 phenotype in vitro, and cytokines produced by Th2 cells generally suppress EAE. Activated microglia also are believed to contribute to MS pathology; perhaps due in part to production of nitric oxide (NO) and TNF-alpha, molecules which can be toxic to CNS cells, including oligodendrocytes. We are currently investigating the role of sex steroids in modulating microglial cell function in relation to MS. It is hoped that elucidation of the mechanisms by which sex steroids modulate CNS inflammation will lead to future therapies in the treatment of MS.
多发性硬化症（MS）在女性中比男性更常见。然而，导致MS性别差异的机制尚不清楚。几项研究表明，性类固醇会影响MS的发展和严重程度。例如，怀孕会影响MS症状，在妊娠晚期症状缓解，随后在产后加重。此外，含有女性性类固醇的口服避孕药与患MS的风险较低和残疾程度降低有关。实验性自身免疫性脑脊髓炎（EAE）是一种由针对中枢神经系统（CNS）抗原的T细胞引发的自身免疫性疾病。EAE的特征是CNS的炎症和脱髓鞘，以及间歇性麻痹——这些特征与MS一致。最近的研究表明，女性性类固醇可能至少部分地通过对T细胞的作用来调节EAE。例如，性类固醇在体外使T细胞向Th2表型转变，而Th2细胞产生的细胞因子通常会抑制EAE。活化的小胶质细胞也被认为与MS病理有关；这可能部分归因于一氧化氮（NO）和肿瘤坏死因子-α的产生，这些分子对包括少突胶质细胞在内的CNS细胞有毒性。我们目前正在研究性类固醇在调节与MS相关的小胶质细胞功能中的作用。希望阐明性类固醇调节CNS炎症的机制将为MS的治疗带来未来的疗法。
