Tumor necrosis factor alpha (TNF-α) blockade improves natural killer cell (NK) activation, hypertension, and mitochondrial oxidative stress in a preclinical rat model of preeclampsia

Hypertens Pregnancy. 2020 Nov;39(4):399-404. doi: 10.1080/10641955.2020.1793999. Epub 2020 Jul 10.

Abstract

The RUPP rat model of Preeclampsia exhibits hypertension (MAP), cytolytic natural killer (cNK) cells, tumor necrosis factor alpha (TNF-α) and mitochondrial Reactive Oxygen Species (mt ROS). Objective: Does TNF-α blockade with ETAN (Etanercept) decrease cNK cell and mt ROS in RUPP rats.

Methods: On gestational day 14, RUPP surgery was performed, ETAN (0.4 mg/kg) was administered on day 18, MAP, blood and tissues collected on 19.

Results: MAP, cytolytic NK cells and mt ROS were elevated in RUPP vs. NP and normalized with ETAN.

Conclusion: TNF-α blockade lowered blood pressure and improve inflammation and organ function in response to placental ischemia.

Keywords: Hypertension; inflammation and oxidative stress.

MeSH terms

  • Animals
  • Blood Pressure / drug effects*
  • Disease Models, Animal
  • Etanercept / pharmacology
  • Etanercept / therapeutic use*
  • Female
  • Killer Cells, Natural / drug effects*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects*
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / metabolism
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor Inhibitors / pharmacology
  • Tumor Necrosis Factor Inhibitors / therapeutic use*

Substances

  • Tumor Necrosis Factor Inhibitors
  • Etanercept