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Interleukin-4 supplementation improves the pathophysiology of hypertension in response to placental ischemia in RUPP rats

Item Type:Article
Title:Interleukin-4 supplementation improves the pathophysiology of hypertension in response to placental ischemia in RUPP rats
Creators Name:Cottrell, J.N. and Amaral, L.M. and Harmon, A.C. and Cornelius, D.C. and Cunningham, M.W. and Vaka, V.R. and Ibrahim, T. and Herse, F. and Wallukat, G. and Dechend, R. and LaMarca, B.D.
Abstract:Preeclampsia (PE) is characterized by chronic inflammation, elevated agonistic autoantibodies to the Angiotensin II type 1 receptor (AT1-AA), ET-1, and uterine artery resistance index (UARI) during pregnancy. Previous studies report an imbalance among immune cells with TH2 being decreased during PE. We hypothesized that Interleukin-4 (IL-4) would increase TH2s and improve the pathophysiology observed in response to placental ischemia during pregnancy. IL-4, 600 ng/day, was administered via a mini-osmotic pump on day 14 of gestation into normal pregnant (NP) and RUPP rats. Carotid catheters were inserted and Doppler ultrasound performed on gestation day 18. Blood pressure (MAP), TNF-α, IL-6, AT1-AA, NK cells, TH2 and B cells were measured on GD 19. MAP in normal pregnant (NP) rats (n=9) was 97 + 2, 101 + 3 in NP+IL-4 rats (n=14), 137 + 4 mmHg in RUPP rats (n=8), which improved to 108 + 3 mmHg in RUPP+IL-4 rats (n=17), p< 0.05. UARI was 0.5+0.03 in NP, 0.8 in RUPP and normalized to 0.5 in RUPP+IL-4 rats, p< 0.05. Plasma nitrate nitrite levels increased in RUPP+IL-4 rats while placental PPET-1 expression, plasma TNF-α and IL-6 and AT1-AA decreased in RUPP+IL-4 rats compared to untreated RUPPs, p< 0.05. Circulating B cells and placental cytolytic NK cells decreased after IL-4 administration while TH2 cells were increased in RUPP+IL-4 treated rats compared to RUPP control rats. This study illustrates IL-4 decreased inflammation and improved TH2 numbers in RUPP rats which ultimately improved hypertension in response to placental ischemia during pregnancy.
Keywords:Preeclampsia, Interleukin-4, Inflammation, Pregnancy, Animals, Rats
Source:American Journal of Physiology Regulatory Integrative and Comparative Physiology
ISSN:0363-6119
Publisher:American Physiological Society (U.S.A.)
Volume:316
Number:2
Page Range:R165-R171
Date:February 2019
Official Publication:https://doi.org/10.1152/ajpregu.00167.2018
PubMed:View item in PubMed

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