Abstract 295: Proliferation of Endogenous T-reg cells Improves the Pathophysiology Associated with Placental Ischemia of Pregnancy

Abstract

Preeclampsia (PE), new onset of hypertension during pregnancy, is associated with pro-inflammatory cytokines and decreased regulatory immune responses including Tregs and decreased IL-10. We believe this decrease in immune regulatory mechanisms leads to much of the pathophysiology associated with PE such as elevated blood pressure and decrease in fetal weight. The RUPP rat model of induced placental ischemia exhibits similar characteristics as women with PE regarding high blood pressure, cytokine levels and immune cell activation and decreased Tregs and pup weight. Therefore, we hypothesized that administration of a CD28 superantagonist (SA) would increase the Treg profile in the RUPP rats which could reduce pro-inflammatory cytokines and blood pressure. Chronic Reduced Uterine Perfusion Pressure, the RUPP procedure, was performed at gestation day 14 (GD14); SA was administered intraperitoneally at GD15, GD18 carotid catheters inserted, and GD19 MAP and pup weight, serum and tissues were collected. MAP in NP rats was 99.5 +/- 2.1, in 116.6 +/- 2.04 in RUPPs which decreased to 107.8 +/- 2.1 mmHg in RUPP+SA. Circulating FoxP3+ Treg cells were undetectable in RUPP rats but increased to 10.96% in RUPP+SA. IL-10 was 24.6 +/- 13 in NP, 35.6 +/- 17 in RUPP and 158.7 +/- 120 pg/mL in RUPP+SA; IL-2 was 6.8 +/- 6 in NP, 89.4 +/- 24 in RUPP, and 126.3+/- 23.7 pg/mL in RUPP+SA. Pup weight was 2.135 +/- 0.23 in NP, 1.964 +/- 0.13 in RUPP, but increased to 2.127 +/- 0.13 mg in RUPP+SA. These data suggest an important role for up-regulating Treg cells to enhance the immune regulatory interactions and inhibit the hypertension while safely improving pup weight in response to placental ischemia during pregnancy.