Effect of Pregnancy on EAE and MS

妊娠对 EAE 和 MS 的影响

• 批准号: 6847787
• 负责人: CAROLINE C WHITACRE
• 金额: $ 34.57万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6847787
• 关键词: RNase protection assay; cytokine; disease /disorder model; enzyme linked immunosorbent assay; experimental allergic encephalomyelitis; gender difference; genetic strain; genetic susceptibility; genetically modified animals; hormone regulation /control mechanism; laboratory mouse; multiple sclerosis; pathologic process; pregnancy; relapse /recurrence; sex hormones; steroid hormone; stress proteins

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), which is more prevalent in women than men (2-3:1). During pregnancy, there is a decrease in the MS relapse rate, most prominent during the third trimester. After parturition, there is often an increase in the relapse rate. Therefore, within a 6 month time frame, there is a profound change in MS disease activity, with both improvement and disease worsening, providing an ideal window of opportunity for study. We are currently working in the area of sex differences in autoimmune disease, focusing on sex differences in susceptibility to experimental autoimmune encephalomyelitis (EAE), a model for MS. As shown in the preliminary results section, we have identified three differing patterns of disease in the B10.PL, SJL and C57BL/6 mouse strains, respectively, and we plan to utilize all three strains to explore the effects of pregnancy on EAE. We have obtained preliminary data showing that immunization of mice during mid-pregnancy or late-pregnancy suppresses the clinical signs of EAE. The goal of this application is to test the hypothesis that disease fluctuation occurring during and soon after pregnancy in MS and EAE are related to changes in the immune response and are influenced by sex and stress steroid hormones. The aims explore the effect of pregnancy on mice with chronic relapsing EAE and the mechanism of that disease modulation. Specifically, the aims are 1) to determine the effect of pregnancy on murine chronic relapsing EAE exploring the effects of pregnancy on three different EAE models differing in genetic background and extent of disease severity, 2) To probe the mechanism of pregnancy effects in EAE by examining the role of cytokine shifts as well as the influences of sex and stress steroid hormones, and 3) To examine the effect of pregnancy on the naive immune system relative to a biased and activated immune response. The long-term goal of this project is to gain a better understanding of the events and mechanisms underlying the pregnancy-induced suppression of EAE and MS.

描述（由申请人提供）：多发性硬化症（MS）是一种中枢神经系统（CNS）脱髓鞘疾病，女性比男性更常见（2-3:1）。怀孕期间，多发性硬化症复发率会下降，在妊娠晚期最为明显。产后，复发率往往会增加。因此，在 6 个月的时间范围内，多发性硬化症疾病活动性发生了深刻的变化，既有改善，也有病情恶化，为研究提供了理想的机会窗口。我们目前正在研究自身免疫性疾病的性别差异领域，重点关注实验性自身免疫性脑脊髓炎（EAE）（MS 的一种模型）易感性的性别差异。如初步结果部分所示，我们分别在 B10.PL、SJL 和 C57BL/6 小鼠品系中鉴定出三种不同的疾病模式，我们计划利用这三种品系来探索妊娠对 EAE 的影响。我们获得的初步数据表明，在怀孕中期或晚期对小鼠进行免疫可以抑制 EAE 的临床症状。该应用的目的是检验以下假设：MS 和 EAE 怀孕期间和怀孕后不久发生的疾病波动与免疫反应的变化有关，并受到性和应激类固醇激素的影响。目的探讨妊娠对患有慢性复发性 EAE 的小鼠的影响以及该疾病的调节机制。具体来说，目的是 1) 确定妊娠对小鼠慢性复发性 EAE 的影响，探索妊娠对遗传背景和疾病严重程度不同的三种不同 EAE 模型的影响，2) 通过以下方式探讨妊娠对 EAE 的影响机制：检查细胞因子变化的作用以及性和应激类固醇激素的影响，以及3）检查怀孕对幼稚免疫系统相对于偏向和激活的免疫反应的影响。该项目的长期目标是更好地了解妊娠引起的 EAE 和 MS 抑制的事件和机制。