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）是中枢神经系统（CNS）的脱髓鞘疾病，在女性中比男性更普遍（2-3：1）。在怀孕期间，MS复发率降低，在三个月期间最突出。分娩后，复发率通常会增加。因此，在6个月的时间范围内，MS疾病活动发生了深刻的变化，随着疾病的改善和疾病恶化，提供了理想的学习机会之窗。我们目前正在自身免疫性疾病的性别差异领域工作，重点是对实验性自身免疫性脑脊髓炎（EAE）的易感性差异，这是MS的模型。如“初步结果”部分所示，我们分别确定了B10.PL，SJL和C57BL/6小鼠菌株中的三种不同的疾病模式，我们计划利用所有三种菌株来探索EAE妊娠对EAE的影响。我们已经获得了初步数据，表明在怀孕或晚期妊娠中，小鼠的免疫抑制了EAE的临床体征。该应用的目的是检验以下假设：MS和EAE怀孕期间和不久后发生的疾病波动与免疫反应的变化有关，并受性别和压力类固醇激素的影响。该目的探索了妊娠对慢性复发EAE的影响以及该疾病调节的机制。具体而言，目的是1）确定怀孕对鼠类慢性慢性复发的影响，探索怀孕对三种不同的EAE模型的影响，在遗传背景和疾病严重程度的遗传背景和程度上有所不同，2）探测通过检查细胞因子转移的作用以及对性降低的影响，并检查妊娠的作用，以检查妊娠的作用，并检查妊娠的影响，并检查妊娠的影响，并培养了一位妊娠的影响。并激活免疫反应。该项目的长期目标是更好地了解妊娠引起的EAE和MS的事件和机制。