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Administration of interleukin-17 soluble receptor C suppresses T(H)17 cells, oxidative stress, and hypertension in response to placental ischemia during pregnancy

Authors

  • D.C. Cornelius
  • J.P. Hogg
  • J. Scott
  • K. Wallace
  • F. Herse
  • J. Moseley
  • G. Wallukat
  • R. Dechend
  • B. Lamarca

Journal

  • Hypertension

Citation

  • Hypertension 62 (6): 1068-1073

Abstract

  • Preeclampsia, new onset hypertension with proteinuria during pregnancy, is associated with chronic inflammation and placental oxidative stress (ROS). Chronic interleukin-17 (IL-17) increases blood pressure, autoantibodies (angiotensin II type I receptor [AT1-AA]), and ROS during pregnancy. The objective of this study was to determine whether T-helper 17 (TH17) suppression via IL-17 recombinant receptor C (IL-17RC) decreases pathophysiology associated with placental ischemia (reduced uterine perfusion pressure [RUPP]). On gestation day 14, miniosmotic pumps infusing 100 pg of IL-17RC per day were implanted into pregnant rats undergoing RUPP. On gestation day 18, carotid catheters were inserted. On gestation day 19, mean arterial pressure was recorded and TH17 cells, oxidative stress, and AT1-AA were measured and analyzed via 1-way ANOVA. Mean arterial pressure increased from 101+-2 mm Hg in normal pregnant rats (n=19) to 120+-1 mm Hg in RUPP rats (n=17) but decreased to 110+-2 mm Hg in RUPP+IL-17RC rats (n=22). Pup weight decreased from 2.28+-0.2 g in normal pregnant rats to 1.96+-0.3 g in RUPP rats but was significantly increased to 2.01+-0.1 in RUPP+IL-17RC rats. TH17 cells were 1.77% in RUPP rats but decreased to 0.65% in RUPP+IL-17RC rats. Urinary isoprostanes were normalized in RUPP+IL-17RC rats (52 pg/{my}g) compared with 89 pg/{my}g in RUPP controls. Placental ROS was 652 relative light units in RUPP rats but decreased to 337 relative light units in RUPP+IL-17RC rats. AT1-AA was 17.27+-0.7 bpm in RUPP rats but decreased to 5.00+-0.5 bpm in RUPP+IL-17RC rats. With this study, we show that infusion of IL-17RC blunts TH17s, oxidative stress, AT1-AA, and hypertension in the RUPP model of preeclampsia, indicating that TH17 cells may play an important role in disease pathophysiology.


DOI

doi:10.1161/HYPERTENSIONAHA.113.01514