Cotreatment With Interleukin 4 and Interleukin 10 Modulates Immune Cells and Prevents Hypertension in Pregnant Mice

被引:56
作者
Chatterjee, Piyali [1 ]
Chiasson, Valorie L. [1 ]
Seerangan, Geetha [1 ]
Tobin, Richard P. [2 ]
Kopriva, Shelley E. [1 ]
Newell-Rogers, M. Karen [2 ]
Mitchell, Brett M. [1 ]
机构
[1] Baylor Scott & White Hlth, Texas A&M Hlth Sci Ctr, Dept Internal Med, Temple, TX 76508 USA
[2] Baylor Scott & White Hlth, Texas A&M Hlth Sci Ctr, Dept Surg, Temple, TX USA
关键词
blood pressure; endothelial dysfunction; hypertension; interleukin; polyinosinic polycytidylic acid; preeclampsia; proteinuria; CYTOKINE PROFILE; PREECLAMPSIA; IL-10; TH1; DEFICIENCY; EXPRESSION; RECEPTOR; THERAPY; CYTOTROPHOBLASTS; ABORTIONS;
D O I
10.1093/ajh/hpu100
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
BACKGROUND Excessive maternal immune system activation plays a central role in the development of the hypertensive disorder of pregnancy preeclampsia (PE). The immunomodulatory cytokines interleukin 4 (IL-4) and interleukin 10 (IL-10) are dysregulated during PE; therefore we hypothesized that treatment with both recombinant IL-4 and IL-10 during pregnancy could prevent the development of PE in mice. METHODS Using our mouse model of PE in which immune system activation is induced by the double-stranded RNA receptor agonist poly I:C, we gave daily injections of IL-4, IL-10, or both on days 13-17 of pregnancy. Mice were then killed on day 18. RESULTS Poly I:C caused a significant increase in systolic blood pressure in pregnant (P-PIC) mice compared with vehicle-treated pregnant (P) mice. All 3 treatments significantly decreased blood pressure in P-PIC mice to P levels, ameliorated the endothelial dysfunction, and decreased placental TLR3 levels in P-PIC mice. However, only IL-4/IL-10 cotreatment prevented the proteinuria and increased incidence of fetal demise in P-PIC mice; IL-4 or IL-10 alone had no effect. Additionally, only IL-4/IL-10 cotreatment prevented the significant increase in CD3(+)/gamma delta(+) T cells and CD11c(+) dendritic cells and significant decrease in CD11b(+)/CD14(-) suppressor monocytes, as well as completely prevented placental necrosis, in P-PIC mice. Importantly, IL-4/IL-10 cotreatment in P mice had no detrimental effects. CONCLUSIONS Taken together, these data demonstrate that exogenous IL-4 and IL-10 administration concurrently during pregnancy can normalize immune cell subsets and prevent PE induced by maternal immune system activation.
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收藏
页码:135 / 142
页数:8
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