Anti-hypertensive drugs alter cytokine production from preeclamptic placentas and peripheral blood mononuclear cells

Hypertens Pregnancy. 2007;26(3):343-56. doi: 10.1080/10641950701380958.

Abstract

Objective: Antihypertensive drugs are administered to women with preeclampsia to control blood pressure and fluid overload. Whether they modulate placental or circulating cytokine production in women with preeclampsia is unknown. This study examines the effect of pharmacological doses of antihypertensive drugs on the production of IL-10, tumor necrosis factor alpha (TNF-alpha), and IL-6 in placental tissue and peripheral blood mononuclear cells (PBMCs) from women with preeclampsia.

Methods: Term placenta samples (n = 6) and PBMCs from whole blood (n = 6) were obtained from women with preeclampsia. Both villous explants and PBMCs were cultured with increasing concentrations of antihypertensive drugs (clonidine, diazoxide, hydralazine, and furosemide). The dose effect of drugs on the production of placental and circulating cytokines IL-10, TNF-alpha, and IL-6 was examined by enzyme-linked immunosorbent assay (ELISA).

Results: Our data suggest that clonidine can stimulate anti-inflammatory IL-10 production from PBMC while decreasing pro-inflammatory TNF-alpha, whereas low doses of hydralazine increased the production of IL-10, TNF-alpha, and IL-6 from preeclamptic PBMCs. There was a reduction in IL-10, TNF-alpha, and IL-6 production with increasing doses of clonidine and hydralazine by placentas in preeclampsia. IL-10, TNF-alpha, and IL-6 production from preeclamptic placenta and PBMCs were inhibited by diazoxide and furosemide.

Conclusions: Antihypertensive drugs may alter Th1/Th2 cytokine balance in preeclamptic tissues in vitro.

MeSH terms

  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Cytokines / metabolism*
  • Female
  • Humans
  • In Vitro Techniques
  • Interleukin-10 / metabolism
  • Interleukin-16 / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Placenta / drug effects*
  • Placenta / metabolism
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / metabolism
  • Pregnancy
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antihypertensive Agents
  • Cytokines
  • Interleukin-16
  • Tumor Necrosis Factor-alpha
  • Interleukin-10