Infection, Inflammation and Preeclampsia

感染、炎症和先兆子痫

• 批准号: 7141015
• 负责人: CATHERINE L HAGGERTY
• 金额: $ 61.77万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7141015
• 关键词: clinical research; cytokine; infection; inflammation; preeclampsia; pregnancy

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.

描述（由申请人提供）：先兆子痫是人类妊娠期的一种疾病，会导致相当高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，并且可能与血管内母体过度炎症反应有关。已知原发感染和与细胞因子产生上调相关的多态性会引发这种炎症反应。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。我们建议在围产期合作项目（n = 55,908）和丹麦国家出生队列（n = 101,046）中开展平行病例对照调查。利用储存的第一次产前检查和产后血清样本，我们建议：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）与风险之间的关系先兆子痫； 2）考察早孕细胞因子、CRP与先兆子痫的关系； 3）调查影响感染状态的多种因素及其与先兆子痫的关系； 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观点将有助于深入了解这种疾病的病理生理学。此外，它还建议采取公共卫生措施，例如育龄妇女的普遍 HSV 和 CP 筛查、治疗和疫苗接种，或高危妇女的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先兆子痫风险的女性的有效工具。