Infection, Inflammation and Preeclampsia

描述（由申请人提供）：子痫前期是一种人类妊娠疾病，可引起相当大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，并可能与过度的母体血管内炎症反应有关。已知原发感染和与细胞因子产生上调相关的多态性可引发这种炎症反应。此外，感染因子和细胞因子可能通过诱导母体炎症介质和生长因子来激活内皮细胞。我们建议平行病例对照调查，嵌套在合作围产期项目（n = 55,908）和丹麦国家出生队列（n = 101,046）中。利用首次产前访视和产后血清样本，我们拟：1)确定母亲原发感染单纯疱疹病毒(HSV)-1、HSV-2、巨细胞病毒（CMV）、肺炎衣原体（CP）与子痫前期风险的关系；2)探讨妊娠早期细胞因子、CRP与子痫前期的关系；3)探讨影响感染状况的多种因素及其与子痫前期的关系；4)研究细胞因子簇并确定它们与子痫前期的关系。感染和炎症可能引发子痫前期的概念将为这种情况的病理生理学提供见解。此外，它还建议采取公共卫生措施，如对育龄妇女进行普遍的HSV和CP筛查、治疗和疫苗接种，或对高危妇女进行阿司匹林和抗氧化治疗。最后，细胞因子和CRP检测可能被证明是识别有子痫前期风险的女性的有效工具。

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.