A RHESUS MONKEY MODEL OF MALARIA DURING PREGNANCY

怀孕期间疟疾的恒河猴模型

• 批准号: 7562248
• 负责人: BILLIE B DAVISON
• 金额: $ 3.04万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562248
• 关键词: Computer Retrieval of Information on Scientific Projects Database; Fetal Death; Funding; Goals; Grant; Immunologics; Infection; Institution; Low Birth Weight Infant; Macaca mulatta; Malaria; Modeling; Plasmodium; Plasmodium malariae; Pregnancy; Preparation; Prospective Studies; Research; Research Personnel; Resources; Saline; Serum; Source; TNFR-Fc fusion protein; TimeLine; Toxic effect; Tumor Necrosis Factor-alpha; United States National Institutes of Health; fetal; human TNF protein; infant outcome; peripheral blood; receptor; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We developed a rhesus monkey model to examine the effects of malaria (Plasmodium coatneyi) during pregnancy. This project, supported by an NIH R01, explores maternal immunologic responses, In a prospective study of rhesus monkeys inoculated with Plasmodium coatneyi or saline on an infection/gestational timeline, we determined the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble tumor necrosis factor receptor type I (sTNFR-I), and soluble tumor necrosis factor receptor type II (sTNFR-II) in peripheral blood throughout primigravid pregnancy, malaria infection, and a combination of the two. Our goal was to determine the association between levels of TNF-alpha and of its 2 soluble receptors and the course of pregnancy and/or malaria and infant outcome. We found that any detectable level of TNF-alpha was always associated with fetal death and that the sTNFRs may be important for fetal protection, possibly through neutralizing the toxic effects of TNF-alpha. Our findings also showed that increased levels of sTNFR-II were associated specifically with malaria and not with normal pregnancy or even pregnancy with low birth weight due to other causes. In contrast, increases in sTNFR-I levels during the later half of normal pregnancies indicate that sTNFR-I may be important in regulating TNF-alpha levels in preparation for normal labor and delivery.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们开发了恒河猴模型来检查怀孕期间疟疾（科氏疟原虫）的影响。该项目由 NIH R01 支持，探索母体免疫反应。在一项针对在感染/妊娠时间线上接种科特尼疟原虫或生理盐水的恒河猴的前瞻性研究中，我们测定了肿瘤坏死因子-α (TNF-α) 的血清水平初孕期间外周血中可溶性肿瘤坏死因子受体 I 型 (sTNFR-I) 和可溶性肿瘤坏死因子受体 II 型 (sTNFR-II)怀孕、疟疾感染以及两者的结合。我们的目标是确定 TNF-α 及其 2 种可溶性受体的水平与妊娠过程和/或疟疾和婴儿结局之间的关联。我们发现，任何可检测到的 TNF-α 水平总是与胎儿死亡相关，并且 sTNFR 可能通过中和 TNF-α 的毒性作用，对胎儿保护很重要。我们的研究结果还表明，sTNFR-II 水平升高与疟疾特别相关，而与正常妊娠甚至由于其他原因导致的低出生体重妊娠无关。相反，正常妊娠后半段sTNFR-I水平的增加表明sTNFR-I可能在调节TNF-α水平以准备正常分娩和分娩方面发挥重要作用。