Scott and White Memorial Hospital, Department of Internal Medicine, Temple, Texas, USA.
Am J Hypertens. 2009 Oct;22(10):1107-14. doi: 10.1038/ajh.2009.125. Epub 2009 Jul 16.
Hypertensive disorders of pregnancy, including preeclampsia (PE), affect approximately 7-10% of pregnancies in the US. Clinical and experimental studies strongly suggest that the maternal immune system plays a role in the development of these disorders; however, few therapeutic options exist aside from delivery.
Using a deoxycorticosterone acetate (DOCA)/salt-low renin rat model, which exhibits hypertension, proteinuria, endothelial dysfunction, and intrauterine growth restriction (IUGR), we measured serum cytokine levels as an indication of immune system activation. In addition, we suppressed the immune system with either azathioprine (Aza) or mycophenolate mofetil (MMF) during the second half of pregnancy to determine whether the these symptoms could be ameliorated.
Our results demonstrate that serum T helper-1 (Th1)-type inflammatory cytokines interleukin (IL)-2, IL-12, interferon-gamma (IFNgamma), and RANTES were significantly elevated in hypertensive pregnant rats while the Th2-type cytokine IL-4 was elevated in normal pregnant animals. Either Aza or MMF significantly attenuated the hypertension, proteinuria, and endothelial dysfunction as well as the increased proinflammatory Th1 cytokine profile in pregnant rats treated with DOCA/salt, and had no effect on these parameters in normal pregnant rats.
These data strongly suggest that maternal immune system activation plays a role in the development of pregnancy-induced hypertension (PIH).
妊娠高血压疾病，包括先兆子痫（PE），在美国约影响 7-10%的妊娠。临床和实验研究强烈表明，母体免疫系统在这些疾病的发展中起作用；然而，除了分娩之外，几乎没有治疗选择。
我们使用去氧皮质酮乙酸盐（DOCA）/盐-低肾素大鼠模型，该模型表现出高血压、蛋白尿、内皮功能障碍和宫内生长受限（IUGR），测量了血清细胞因子水平，作为免疫系统激活的指标。此外，我们在妊娠后半期用硫唑嘌呤（Aza）或霉酚酸酯（MMF）抑制免疫系统，以确定这些症状是否可以改善。
我们的结果表明，血清辅助性 T 细胞-1（Th1）-型炎症细胞因子白细胞介素（IL）-2、IL-12、干扰素-γ（IFNγ）和 RANTES 在高血压妊娠大鼠中显著升高，而 Th2 型细胞因子 IL-4 在正常妊娠动物中升高。Aza 或 MMF 均显著减轻 DOCA/salt 治疗的妊娠大鼠的高血压、蛋白尿和内皮功能障碍以及促炎 Th1 细胞因子谱的增加，而对正常妊娠大鼠的这些参数没有影响。
这些数据强烈表明，母体免疫系统激活在妊娠高血压（PIH）的发展中起作用。
