Interleukin-4 deficiency induces mild preeclampsia in mice
Interleukin-4 deficiency induces mild preeclampsia in mice
复制标题
DOI：
10.1097/hjh.0b013e328360ae6c
复制
发表时间：
2013-07-01
影响因子：
4.9
通讯作者：
Mitchell, Brett M.
中科院分区：
文献类型：
--
作者：
Chatterjee, Piyali;Kopriva, Shelley E.;Mitchell, Brett M.
目的：炎症是成功妊娠的必要条件，然而，过度炎症在妊娠高血压疾病先兆子痫的发展中起着核心作用。许多抗炎细胞因子在先兆子痫妇女中减少，但个别细胞因子在妊娠期间血压调节中的作用尚不清楚。因此，我们研究了是否缺乏有效的抗炎细胞因子白细胞介素-4（IL-4）将足以引起小鼠先兆子痫样综合征，并且当与免疫系统激活相结合时，这些症状将进一步增强。方法：在妊娠IL-4缺陷小鼠以及用Toll样受体3激动剂聚肌胞苷处理的妊娠IL-4缺陷小鼠中进行脾免疫细胞、胎盘炎症、血压、内皮功能和尿蛋白排泄的测量。结果：与妊娠对照小鼠相比，妊娠IL-4缺陷小鼠表现出脾免疫细胞亚群改变，促炎细胞因子水平升高，胎盘炎症，轻度高血压，内皮功能障碍和蛋白尿。与妊娠对照组小鼠治疗聚I：C表现出先兆子痫样症状相比，聚I：C治疗的妊娠IL-4缺陷小鼠表现出进一步增加促炎细胞因子水平，这是与增强SBP和内皮功能障碍。结论：总的来说，这些数据表明，IL-4的情况下是足以诱导轻度先兆子痫样症状的小鼠由于过度炎症。因此，IL-4的抗炎作用在预防妊娠期高血压中是重要的。
Objective:Inflammation is necessary for successful pregnancy; however, excessive inflammation plays a central role in the development of the pregnancy-specific hypertensive disorder preeclampsia. Numerous anti-inflammatory cytokines are decreased in women with preeclampsia but the role of individual cytokines in blood pressure regulation during pregnancy is unknown. Therefore, we examined whether the lack of the potent anti-inflammatory cytokine interleukin-4 (IL-4) would be sufficient to elicit a preeclampsia-like syndrome in mice, and when coupled with immune system activation that these symptoms would be further augmented.Methods:Measures of splenic immune cells, placental inflammation, blood pressure, endothelial function, and urinary protein excretion were performed in pregnant IL-4-deficient mice as well as in pregnant IL-4-deficient mice treated with the Toll-like receptor 3 agonist polyinosinic:polycytidylic (poly I:C).Results:Pregnant IL-4-deficient mice exhibited altered splenic immune cell subsets, increased levels of pro-inflammatory cytokines, placental inflammation, mild hypertension, endothelial dysfunction, and proteinuria compared to pregnant control mice. Compared to pregnant control mice treated with poly I:C which exhibit preeclampsia-like symptoms, poly I:C-treated pregnant IL-4-deficient mice exhibited a further increase in pro-inflammatory cytokine levels, which was associated with augmented SBP and endothelial dysfunction.Conclusion:Collectively, these data show that the absence of IL-4 is sufficient to induce mild preeclampsia-like symptoms in mice due to excessive inflammation. Thus, the anti-inflammatory effects of IL-4 are important in preventing hypertension during pregnancy.