A RHESUS MONKEY MODEL OF MALARIA DURING PREGNANCY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们开发了一个恒河猴模型来研究怀孕期间疟疾(衣原体)的影响。在NIH R01的支持下，该项目探索了母体免疫反应，在一项针对感染/妊娠时间线上接种Coatneyi疟原虫或生理盐水的恒河猴的前瞻性研究中，我们检测了初孕、疟疾感染以及两者结合过程中外周血中肿瘤坏死因子-α(TNF-α)、可溶性肿瘤坏死因子受体I(sTNFR-I)和可溶性肿瘤坏死因子受体II(sTNFR-II)的水平。我们的目标是确定肿瘤坏死因子-α及其2个可溶性受体的水平与妊娠和/或疟疾的病程和婴儿结局之间的关系。我们发现，任何可检测到的肿瘤坏死因子-α水平都与胎儿死亡有关，sTNFR可能通过中和肿瘤坏死因子-α的毒性效应而对胎儿保护起重要作用。我们的研究结果还表明，sTNFR-II水平的升高与疟疾有特定的相关性，而与正常妊娠或因其他原因导致的低出生体重妊娠无关。相反，正常妊娠后期sTNFR-I水平的升高表明，sTNFR-I可能在为正常分娩和分娩准备过程中调节肿瘤坏死因子-α水平方面发挥重要作用。

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.