The Role of Interleukin‐2 (IL‐2) in Natural Killer Cell (NK) Activation and Hypertension in a Preclinical Rat Model of Preeclampsia

Abstract

Women with preeclampsia (PE) have hypertension, placental ischemia, increased pro‐inflammatory cells (natural killer (NK) and Th1 cells) and cytokines, and intrauterine growth restriction (IUGR). Interleukin‐2 (IL‐2) is a Th1 cytokine that stimulates NK cell activation. We hypothesize that IL‐2 is one mechanism whereby Th1 cells, which are activated in response to placental ischemia, mediate NK cell activation, hypertension, and IUGR during pregnancy. The objective of this study was 2 fold: 1.) to determine if elevated IL‐2 during pregnancy will increase blood pressure, NK cell activation, and cause IUGR. 2.) to determine if blockade of IL‐2 (basiliximab) will decrease blood pressure, NK cell activation, and improve pup weight in the reduce uterine perfusion pressure (RUPP) preclinical rat model of PE The RUPP rat is a model of placental ischemia during pregnancy which has increased IL‐2 levels and mimics many of the symptoms of PE.MethodsOn gestational day 14, normal pregnant (NP) rats received IL‐2 infusion (0.20 ng/ml) via mini‐osmotic pump; while RUPP rats receive basiliximab (0.07 mg/per rat) via IV infusion. On day 19, conscious blood pressure (MAP), pups, placentas, and blood were collected. Flow cytometry was used for quantification of NK cells.ResultsIL‐2 infusion did not increase MAP (106 ± 3 vs. 100 ± 2 mmHg) nor change pup weight (2.24 ± 0.06 vs. 2.33 ± 0.06 g). However, IL‐2 infusion decreased placental weight (0.60 ± 0.02 vs. 0.67 ± 0.02 g, p<0.05 vs. NP) and increased circulating activated NK cells (10.4 ± 1.8 vs. 3.1 ± 1%, p<0.05 vs. NP). RUPPs rats exhibit elevated MAP (123 ± 3 vs. 103 ± 3 mmHg, p<0.05 vs. NP), placental (14.1 ± 2.9 vs. 7.8 ± 0.6%, p<0.05 vs. NP), and circulating (16.6 ± 1.3 vs. 7.7 ± 0.9%, p<0.05 vs. NP) activated NK cells. Basiliximab treatment had no effect to lower MAP (123 ± 2 vs. 123 ± 3 mmHg) or improve pup weight (2.08 ± 0.07 vs. 2.04 ± 0.07 g) and placental weight (0.59 ± 0.03 vs. 0.53 ±0.04 g) in RUPP rats. However, basiliximab decreased total placental NK cells in RUPP rats (4.6 ± 1.4 vs. 14.1 ± 2.9%, p<0.05 RUPP + basiliximab vs. RUPP).ConclusionIL‐2 appears to play a major role in NK cell activation during PE that could possibly impact placental health without causing increases in blood pressure during pregnancy.Support or Funding InformationResearch Supported by T32HL105324 and HL130456This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.