Estradiol, but not dehydroepiandrosterone, decreases parasitemia and increases the incidence of cerebral malaria and the mortality in Plasmodium berghei ANKA-infected CBA mice
Estradiol, but not dehydroepiandrosterone, decreases parasitemia and increases the incidence of cerebral malaria and the mortality in Plasmodium berghei ANKA-infected CBA mice
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DOI：
10.1159/000093271
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发表时间：
2006-01-01
影响因子：
2.4
通讯作者：
do Nascimento, Jose L. M.
中科院分区：
文献类型：
--
作者：
Libonati, Rosana M. F.;Cunha, Maristela G.;do Nascimento, Jose L. M.
目的：在感染伯氏疟原虫 ANKA 的 CBA 小鼠中评估去势和随后补充脱氢表雄酮 (DHEA) 或雌二醇对寄生虫血症、死亡率和脑型疟疾 (CM) 发病率的影响。方法：对雌性小鼠进行去势，每组 12-15 只动物每天注射 DHEA、雌二醇或盐水。治疗开始四天后，给小鼠接种 1 X 106 个伯氏疟原虫 ANKA 寄生的红细胞。感染后5天内继续进行DHEA治疗，并在随访期间给予雌二醇。每天通过吉姆萨染色的血涂片评估寄生虫血症。 Signs of CM were determined by the manifestation of coma, limb paralysis and/or convulsions.通过夹心 ELISA 评估血浆 TNF-α 水平。采用Bredt和Snyder的方法测量垂死小鼠脑中一氧化氮合酶(NOS)的活性。结果：在未去势的感染小鼠中，与未感染对照小鼠相比，CM 发生率为 50%，血浆 TNF-α 升高，脑 NOS 活性降低。去势对分析参数（寄生虫血症、死亡率、CM 发生率、TNF-α 水平或 NOS 活性）没有重大影响。雌二醇替代疗法可减少寄生虫血症，但会导致 CM 发生率升高和死亡率加快，并且 NOS 活性增加。结论：雌二醇调节伯氏疟原虫 ANKA 感染的 CBA 小鼠的免疫反应，减少寄生虫血症并增加 NOS 活性，并对生存和 CM 发生率产生负面影响，表明神经免疫内分泌相互作用在疟疾感染的生理发病机制中很重要。版权所有 (c) 2006 S. Karger AG，巴塞尔。
Objective: The effect of castration and subsequent replacement of dehydroepiandrosterone (DHEA) or estradiol on parasitemia, mortality and incidence of cerebral malaria (CM) was evaluated in CBA mice infected with Plasmodium berghei ANKA. Methods: Female mice were castrated, and groups of 12-15 animals received daily injections of DHEA, estradiol or saline. Four days after the start of treatment, mice were inoculated with 1 X 106 P. berghei ANKA-parasitized erythrocytes. DHEA treatment was continued during the 5 days after infection, and estradiol was administered during the follow-up. Parasitemia was evaluated daily in Giemsa-stained blood smears. Signs of CM were determined by the manifestation of coma, limb paralysis and/or convulsions. Plasma TNF-alpha levels were evaluated by sandwich ELISA. Nitric oxide synthase (NOS) activity in the brain of moribund mice was measured by the method of Bredt and Snyder. Results: In non-castrated infected mice, the incidence of CM was 50%, and plasma TNF-alpha increased and brain NOS activity decreased compared to non-infected controls. Castration had no major effect on the parameters analyzed (parasitemia, mortality, CM incidence, TNF-alpha levels or NOS activity). Estradiol replacement caused a decrease in parasitemia but resulted in higher CM incidence and faster mortality, with an increase in NOS activity. Conclusions: Estradiol modulated the immune response of P. berghei ANKA-infected CBA mice, decreasing parasitemia and increasing NOS activity, and impacted negatively on survival and CM incidence, showing that neuroirnmunoendocrine interactions are important in the physiopathogenesis of malaria infections. Copyright (c) 2006 S. Karger AG, Basel.