A RHESUS MONKEY MODEL OF MALARIA DURING PREGNANCY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们开发了一个恒河猴模型，以检查疟疾（疟原虫coatneyi）在怀孕期间的影响。本项目由NIH R 01支持，旨在探讨母体免疫反应。在一项前瞻性研究中，我们在感染/妊娠时间轴上对恒河猴接种疟原虫或生理盐水，测定其血清肿瘤坏死因子-α水平。（TNF-α），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）在整个早孕，疟疾感染，以及两者的组合外周血。我们的目标是确定TNF-α及其2种可溶性受体水平与妊娠和/或疟疾过程和婴儿结局之间的关系。我们发现，任何可检测到的TNF-α水平总是与胎儿死亡有关，sTNFRs可能对胎儿保护很重要，可能是通过中和TNF-α的毒性作用。我们的研究结果还表明，sTNFR-II水平的升高与疟疾特异性相关，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，在正常妊娠的后半期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中起重要作用。

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.