Interferon y neutralization reduces blood pressure, uterine artery resistance index, and placental oxidative stress in placental ischemic rats

Preeclampsia (PE) is characterized by maternal hypertension, intrauterine growth restriction, and increased cytolytic natural killer cells (cNKs), which secrete interferon y (IFNy). However, the precise role of IFNy in contributing to PE pathophysiology remains unclear. Using the reduced uterine perfusion pressure (RUPP) rat model of placental ischemia, we tested the hypothesis that neutralization of IFNy in RUPPs will decrease placental reactive oxygen species (ROS) and improve vascular function resulting in decreased MAP and improved fetal growth. On gestation day (GD) 14, the RUPP procedure was performed and on GDs 15 and 18, a subset of normal pregnant rats (NP) and RUPP rats were injected with 10 mu g/kg of an anti-rat IFNy monoclonal antibody. On GD 18, uterine artery resistance index (UARI) was measured via Doppler ultrasound and on GD 19, mean arterial pressure (MAP) was measured, animals were euthanized, and blood and tissues were collected for analysis. Increased MAP was observed in RUPP rats compared with NP and was reduced in RUPP + anti-IFNy. Placental ROS was also increased in RUPP rats compared with NP rats and was normalized in RUPP + anti-IFNy. Fetal and placental weights were reduced in RUPP rats, but were not improved following anti-IFNy treatment. However, UARI was elevated in RUPP compared with NP rats and was reduced in RUPP + anti-IFNy. In conclusion, we observed that IFNy neutralization reduced MAP, UARI, and placental ROS in RUPP recipients. These data suggest that IFNy is a potential mechanism by which cNKs contribute to PE pathophysiology and may represent a therapeutic target to improve maternal outcomes in PE.

Automated summary

In this study, neutralization of IFNy was found to reduce MAP, UARI, and placental ROS levels in RUPP recipients. However, fetal and placental weights in RUPP rats were not improved following anti-IFNy treatment. These findings suggest that IFNy may play a role in the pathophysiology of PE and could be a potential therapeutic target for improving maternal outcomes in PE.