Influence of Lactation on Postpartum Stress and Immunity

描述（由申请人提供）：该修订后的竞争性继续提案是一项资金申请，旨在探索产后期间免疫，内分泌和炎症变化的模式，并分析这些变量和轨迹之间的潜在关系以及产后甲状腺炎（PPT）的发展，产后常见的自身免疫性疾病。最初资助的项目探讨了哺乳状态与产后母亲的压力和免疫力之间的关系。该横断面研究的主要发现是与对照组相比，产后4-6周的妇女中存在细胞因子和蛋白质以及炎症反应的显著上调。这导致了竞争性的继续要求，旨在探索这些变化随时间的模式，从产后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。这种前瞻性的方法也将使我们能够检查内分泌，人口统计学，压力，情绪和免疫变量之间的关系，并确定这些变量预测和伴随PPT的发病和病程。许多自身免疫性疾病在产后发作或发病，母乳喂养会增加风险。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）自身抗体的存在或不存在来确定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，压力和烦躁情绪，一般健康状况以及PPT的发病和病程之间的关系，我们预计约50%的TPO+母亲会发生这种情况。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，并将为将这种生理学与许多孕产妇健康结果联系起来奠定基础。 这项研究对公共卫生的重要性在于女性自身免疫性疾病的突出发病率，以及自身免疫过程导致的衰弱和长期慢性疾病。遗传学仅在这些疾病的发病机制中发挥作用，而环境的作用对于理解至关重要。产后的免疫学和内分泌学为研究自身免疫性疾病提供了一个透镜，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.