Abstract
IL-2 is a cytokine released from CD4+T cells with dual actions and can either potentiate the inflammatory response or quell a chronic inflammatory response depending on its circulating concentration. IL-2 is elevated in many chronic inflammatory conditions and is increased during preeclampsia (PE). PE is characterized by new-onset hypertension during pregnancy and organ dysfunction and increasing evidence indicates that proinflammatory cytokines cause hypertension and mitochondrial (mt) dysfunction during pregnancy. The reduced uterine perfusion pressure (RUPP) model of placental ischemia is a rat model of PE that we commonly use in our laboratory and we have previously shown that low doses of recombinant IL-2 can decrease blood pressure in RUPP rats. The objective of this study was to determine the effects of a low dose of recombinant IL-2 on multi-organ mt dysfunction in the RUPP rat model of PE. We tested our hypothesis by infusing recombinant IL-2 (0.05 ng/mL) into RUPP rats on GD14 and examined mean arterial pressure (MAP), renal, placental and endothelial cell mt function compared to control RUPP. MAP was elevated in RUPP rats (n = 6) compared to controls (n = 5) (122 ± 5 vs. 102 ± 3 mmHg, p < 0.05), but was reduced by administration of LD recombinant IL-2 (107 ± 1 vs. 122 ± 5 mmHg, n = 9, p < 0.05). Renal, placental and endothelial mt ROS were significantly increased in RUPP rats compared to RUPP+ IL-2 and controls. Placental and renal respiration rates were reduced in RUPP rats compared to control rats but were normalized with IL-2 administration to RUPPs. These data indicate that low-dose IL-2 normalized multi-organ mt function and hypertension in response to placental ischemia.
Highlights
Preeclampsia (PE) is a pregnancy associated disorder affecting 5–7% of pregnancies worldwide and is a well-known cause of maternal, fetal, neonatal morbidity and mortality [1]
Results were reported as means ± SEM and considered statistically when p < 0.05. (* p < 0.05 vs. NP control; + p < 0.05 vs. reduced uterine perfusion pressure (RUPP))
Results were reported as means ± SEM and considered statistically significant when p < 0.05. (* p < 0.05 vs. NP control; + p < 0.05 vs. RUPP)
Summary
Preeclampsia (PE) is a pregnancy associated disorder affecting 5–7% of pregnancies worldwide and is a well-known cause of maternal, fetal, neonatal morbidity and mortality [1]. The complex immune response in PE has been associated with inflammatory immune cells and cytokines, which leads to the production of reactive oxygen species (ROS), increased expression of endothelin-1 (ET-1), sFlt-1 and autoantibodies to the angiotensin II type 1 receptor (AT1-AA) [4,5]. Vaka [6] examined mitochondrial (mt) dysfunction and ROS in the RUPP rat model of PE and found that mt dysfunction contributed to the hypertension. We know the importance of renal and placental mt dysfunction in hypertension in the RUPP model of PE, other avenues to lower excessive ROS or improve mt function need to be examined
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