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

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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., Amaral, L.M., Harmon, A.C., Cornelius, D.C., Cunningham, M.W., Vaka, V.R., Ibrahim, T., Herse, F., Wallukat, G., 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
Volume:	316
Number:	2
Page Range:	R165-R171
Date:	February 2019
Official Publication:	https://doi.org/10.1152/ajpregu.00167.2018
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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