title: The reduction of circulating levels of IL-6 in pregnant women with preeclampsia by magnesium sulphate and nifedipine: In vitro evidence for potential mechanisms.
abstract: BACKGROUND
  Women with preeclampsia have elevated levels of inflammatory cytokines including IL-6. IL-6, which is known to activate endothelial cells and induce the production of necrotic trophoblastic debris from the placenta, may be important in the pathogenesis of preeclampsia. MgSO4 is a major therapy for the prevention of seizures in preeclampsia but it has been suggested to also have anti-inflammatory and vasodilatory properties.
  
  
  METHODS
  22 pregnant women with preeclampsia and 68 normotensive controls were recruited and circulating IL-6 levels in these women were measured before MgSO4 and nifedipine treatment and after delivery. In addition, endothelial cells were treated with IL-6 or necrotic trophoblastic debris, generated from first trimester placental explants in the presence or absence of MgSO4in vitro, and cell-surface ICAM-1 was measured by ELISA. The levels of IL-6 in the culture medium were also measured. Furthermore nitric oxide synthetase activity in endothelial cells that had been treated with IL-6 was measured using l-NAME.
  
  
  RESULTS
  Circulating levels of IL-6 in preeclampsia were reduced significantly following administration of MgSO4. In vitro, MgSO4 reversed the activation of endothelial cells induced by IL-6 but not by necrotic trophoblastic debris. The effect of MgSO4 in reversing the IL-6 induced activation of endothelial cells was not dependent upon nitric oxide synthetase. Treating placental explants with MgSO4 prevented the production of necrotic trophoblastic debris induced by IL-6.
  
  
  CONCLUSIONS
  we demonstrated that IL-6 levels drop following treatment with MgSO4 and nifedipine in vivo, and have identified several mechanisms by which this positive effect on IL-6 may occur in vitro.
authors.affiliation: Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand; The Obstetrics and Gynaecology Hospital of Fudan University, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Wuxi Maternity and Children Health Hospital, Nanjing Medical University, China. Electronic address: zmdoc2002@163.com.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.affiliation: The Obstetrics and Gynaecology Hospital of Fudan University, China.
authors.forename: F
authors.initials: F
authors.lastname: Guo
authors.affiliation: Wuxi Maternity and Children Health Hospital, Nanjing Medical University, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Yin
authors.affiliation: Wuxi Maternity and Children Health Hospital, Nanjing Medical University, China.
authors.forename: J P
authors.initials: JP
authors.lastname: Xiao
authors.affiliation: Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand.
authors.forename: P R
authors.initials: PR
authors.lastname: Stone
authors.affiliation: Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand.
authors.forename: L W
authors.initials: LW
authors.lastname: Chamley
mesh_terms: D000293:Adolescent; D000328:Adult; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000494:pharmacology; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D009543:Nifedipine / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011225:Pre-Eclampsia / Q000097:blood* / Q000188:drug therapy*; D011247:Pregnancy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D008278:Magnesium Sulfate; D019001:Nitric Oxide Synthase; D009543:Nifedipine
keywords: Endothelial cell activation; IL-6; MgSO(4); Preeclampsia