Xu Bei, Makris Angela, Thornton Charlene, Ogle Robert, Horvath John S, Hennessy Annemarie
Vascular Immunology Research Laboratory, The Heart Research Institute, University of Sydney, Australia.
J Hypertens. 2006 May;24(5):915-22. doi: 10.1097/01.hjh.0000222762.84605.03.
Antihypertensive drugs such as clonidine, diazoxide, hydralazine and furosemide are used in the hypertensive disorders of pregnancy to control blood pressure, but it is not clear if they modulate the production of placental or circulating cytokines.
To examine the effect of pharmaceutical doses of well known antihypertensive drugs used for blood pressure control on the production of the cytokines interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-alpha in placental tissue and peripheral blood mononuclear cells (PBMCs) in normal pregnancy.
Placental biopsies were taken from the decidual surface of placentas after delivery of normal pregnancies (n = 6) and PBMCs were separated from the whole blood of normal term pregnant women (n = 7). Both villous explants and PBMCs were cultured with increasing concentrations of antihypertensive drugs. The dose effect of drugs on the production of placental and circulating cytokines (IL-6, IL-10 and TNF-alpha) were examined by enzyme-linked immunosorbent assay.
Placental production of IL-10 was not affected by clonidine, but decreased significantly after incubation of the tissue with diazoxide, hydralazine or furosemide. Production of IL-10 by PBMCs increased significantly: by from 3.4 +/- 2.7% [16.3 pg/ml (range 6.1-21.5 pg/ml)] to 24.5 +/- 3.3% [30.4 pg/ml (range 16.9-34.8 pg/ml)] with increasing concentrations of clonidine (0.08-1.3 microg/ml), and by 8.8 +/- 3.5% [4.1 pg/ml (range 3.0-17.8 pg/ml)] and 17.2 +/- 1.9% [22.6 pg/ml (range 13.2-23.2 pg/ml)] with lower doses of hydralazine (6.3 and 12.5 microg/ml) (all P values < 0.05). There was a stepwise reduction in production of TNF-alpha and IL-6 with increasing doses of diazoxide, hydralazine and furosemide by placentas and PBMCs from these women with normal pregnancies.
Our data suggest that the antihypertensive drugs clonidine and hydralazine can stimulate production of the circulating anti-inflammatory cytokine IL-10, whereas furosemide and diazoxide inhibit the production of this cytokine and the proinflammatory cytokines TNF-alpha and IL-6 by placentas and PBMCs.
可乐定、二氮嗪、肼屈嗪和呋塞米等降压药物用于治疗妊娠期高血压疾病以控制血压，但它们是否会调节胎盘或循环细胞因子的产生尚不清楚。
研究用于控制血压的常用降压药物的药理剂量对正常妊娠胎盘组织和外周血单个核细胞（PBMC）中细胞因子白细胞介素（IL）-6、IL-10和肿瘤坏死因子（TNF）-α产生的影响。
在正常妊娠分娩后（n = 6），从胎盘的蜕膜表面取胎盘组织活检，从足月正常妊娠妇女的全血中分离PBMC（n = 7）。将绒毛外植体和PBMC与浓度递增的降压药物一起培养。通过酶联免疫吸附测定法检测药物对胎盘和循环细胞因子（IL-6、IL-10和TNF-α）产生的剂量效应。
可乐定不影响胎盘IL-10的产生，但在用二氮嗪、肼屈嗪或呋塞米孵育组织后，IL-10产生显著降低。PBMC产生的IL-10显著增加：随着可乐定浓度从0.08 - 1.3μg/ml增加，IL-10产生从3.4±2.7%[16.3 pg/ml（范围6.1 - 21.5 pg/ml）]增加到24.5±3.3%[30.4 pg/ml（范围16.9 - 34.8 pg/ml）]，随着较低剂量的肼屈嗪（6.3和12.5μg/ml），IL-10产生分别增加8.8±3.5%[4.1 pg/ml（范围3.0 - 17.8 pg/ml）]和17.2±1.9%[22.6 pg/ml（范围13.2 - 23.2 pg/ml）]（所有P值<0.05）。随着这些正常妊娠妇女的胎盘和PBMC中二氮嗪、肼屈嗪和呋塞米剂量的增加，TNF-α和IL-6的产生呈逐步下降趋势。
我们的数据表明，降压药物可乐定和肼屈嗪可刺激循环抗炎细胞因子IL-10的产生，而呋塞米和二氮嗪则抑制胎盘和PBMC中该细胞因子以及促炎细胞因子TNF-α和IL-6的产生。
