Infection, Inflammation and Preeclampsia

描述（由申请人提供）：先兆子痫是一种人类妊娠疾病，可导致相当多的孕产妇和围产期发病率。内皮损伤和功能障碍被认为发生在疾病过程的早期，可能与母体过度的血管内炎症反应有关。已知与上调的细胞因子产生相关的原发性感染和多态性触发这种炎症反应。此外，感染因子和细胞因子可通过诱导母体炎症介质和生长因子来激活内皮细胞。我们提出了平行的病例对照研究，嵌套在围产期合作项目（n = 55，908）和丹麦国家出生队列（n = 101，046）。本研究利用储存的产前及产后血清标本，探讨孕妇单纯疱疹病毒（HSV）-1、HSV-2、巨细胞病毒（CMV）、衣原体（CP）的原发性感染与子痫前期的关系，以及早孕细胞因子、CRP与子痫前期的关系。3）研究影响感染状态的多种因素及其与先兆子痫的关系;和4）研究细胞因子簇并确定它们与先兆子痫的关联。感染和炎症可能引发先兆子痫的概念将提供对这种情况的病理生理学的了解。此外，它还建议采取公共卫生措施，如在育龄妇女中进行普遍的HSV和CP筛查、治疗和疫苗接种，或在高危妇女中进行阿司匹林和抗氧化剂治疗。最后，细胞因子和CRP检测可能被证明是有效的工具，用于确定妇女在发展先兆子痫的风险。

DESCRIPTION (provided by applicant): Preeclampsia is a disease of human pregnancy that causes considerable maternal and perinatal morbidity. Endothelial injury and dysfunction are thought to occur early in the disease process, and may relate to an excessive intravascular maternal inflammatory response. Primary infections and polymorphisms associated with upregulated cytokine production are known to trigger such an inflammatory response. Furthermore, infectious agents and cytokines may invoke endothelial activation through induction of maternal inflammatory mediators and growth factors. We propose parallel case-control investigations, nested within the Collaborative Perinatal Project (n = 55,908) and the Danish National Birth Cohort (n = 101,046). Using stored first prenatal visit and postnatal serum samples, we propose to: 1) determine the relationship between maternal primary infection with Herpes Simplex Virus (HSV)-1, HSV-2, Cytomegalovirus (CMV), Chlamydia Pneumoniae (CP) and the risk of preeclampsia; 2) examine the relationship between early pregnancy cytokines, CRP and preeclampsia; 3) investigate multiple factors affecting infection status and its relation to preeclampsia; and 4) investigate cytokine clusters and determine their associations with preeclampsia. The notion that infection and inflammation may trigger preeclampsia would provide insight into the pathophysiology of this condition. Further, it would suggest public health measures, such as universal HSV and CP screening, treatment, and vaccination among women of reproductive age, or aspirin and antioxidant therapy among high risk women. Finally, cytokine and CRP testing may prove to be effective tools for identifying women at risk for developing preeclampsia.