Influence of Lactation on Postpartum Stress and Immunity

描述(由申请人提供)：这项修订后的竞争性延续方案是一项资金申请，旨在探索产后免疫、内分泌和炎症变化的模式，并分析这些变量与轨迹之间的潜在关系以及产后甲状腺炎(PPT)的发展，产后甲状腺炎是一种常见的产后自身免疫性疾病。最初的资助项目探索了产后母亲的哺乳状况与压力和免疫力之间的关系。这项横断面研究的主要发现是，与对照组相比，产后4-6周的妇女存在显著的细胞因子和蛋白质上调以及炎症反应。这导致了竞争性的继续要求，试图探索这些变化的模式随着时间的推移，从第一周到产后第六个月，在健康对照母亲和有PPT风险的母亲中。这种前瞻性的方法还将使我们能够检查内分泌、人口统计、压力、情绪和免疫变量之间的关系，并确定这些变量中的哪些变量可以预测和伴随PPT的发病和病程。许多自身免疫性疾病在产后发作或发病，母乳喂养增加了风险。我们将使用PPT作为自身免疫性疾病的模型，并根据妊娠期间测量的甲状腺过氧化物酶(TPO)自身抗体的存在与否来识别PPT组的低风险和高风险。我们将前瞻性地研究免疫和炎症过程和轨迹、母乳喂养状态、产后激素、应激和烦躁情绪、一般健康状况以及PPT的发病和病程之间的关系，我们预计大约50%的TPO+母亲会发生PPT。此外，探索TPO母亲的免疫、炎症和激素的正常变化将提供对产后生理学的新理解，并将为将这一生理学与许多孕产妇健康结局联系起来奠定基础。 这项研究对公共卫生的意义在于女性自身免疫性疾病的突出发病率，以及由于自身免疫过程而导致的衰弱和长期慢性病。遗传学在这些疾病的发病机制中只起到了一部分作用，而环境的作用是理解这些疾病的关键。产后免疫学和内分泌学为研究自身免疫性疾病提供了一个镜头，因为产后是许多自身免疫性疾病发展或恶化的关键时期。

DESCRIPTION (provided by applicant): This revised competing continuation proposal is a request for funding to explore the patterns of immune, endocrine, and inflammatory changes over the postpartum period and to analyze potential relationships between these variables and trajectories as well as the development of postpartum thyroiditis (PPT), a common autoimmune disease of the postpartum. The initial funded project explored the relationship between lactation status and stress and immunity in postpartum mothers. The major findings from that cross sectional study were the presence of significant upregulation of cytokines and proteins and inflammatory responses in 4-6 week postpartum women compared to controls. This has led to the competing continuation request that seeks to explore the pattern of these changes over time, from the first week through the sixth postpartum month, in healthy control mothers and mothers at risk for PPT. This prospective approach will also allow us to examine relationships among endocrine, demographic, stress, mood and immunity variables and determine which of these variables predict and accompany onset and course of PPT. Many autoimmune diseases flare or have their onset in the postpartum, and breastfeeding increases risk. We will use PPT as a model of autoimmune disease, and identify low and high risk for PPT groups on the basis of the presence or absence of thyroid peroxidase enzyme (TPO) autoantibodies measured during pregnancy. We will prospectively study relationships between immune and inflammatory processes and trajectories, breastfeeding status, postpartum hormones, stress and dysphoric moods, general health, and the onset and course of PPT, which we anticipate will occur in about 50% of the TPO+ mothers. In addition, exploration of the normal changes in immunity, inflammation, and hormones in TPO- mothers will provide new understanding about the physiology of the postpartum, and will lay the groundwork for relating this physiology to many maternal health outcomes. The significance of this research to public health lies in the prominent incidences of autoimmune diseases in women, and the debilitating and long-term chronic illnesses that result from autoimmune processes. Genetics only plays a part in the pathogenesis of these illnesses, and the role of environment is critical to understand. The immunology and endocrinology of the postpartum provides a lens through which to study autoimmune disease, as the postpartum is a critical period for development or exacerbation of many autoimmune diseases.