Proliferation Of Endogenous Regulatory T Cells Improve The Pathophysiology Associated With Placental Ischaemia Of Pregnancy

ProblemPreeclampsia (PE) is associated with inflammation and decreased Treg cells and IL-10. The reduced uterine perfusion pressure (RUPP) rat model of PE exhibits these characteristics, and we hypothesized that induction of endogenous Tregs by a specific stimulus (CD28 superagonistic monoclonal antibody) would reduce inflammation, vasoactive factors, and hypertension in RUPP rats.Method of studyRUPP was performed at gestation day (GD) 14; CD28 superagonist was administered intraperitoneally GD15; GD18 carotid catheters were inserted, and GD19 MAP and pup weight, blood, and tissues were collected.ResultsMAP (mmHg) in NP rats was 995 and 122 +/- 2 in RUPPs and was 111 +/- 1mmHg in RUPP+SA. Circulating Tregs were 6 +/- 2% in NP rats and 0.77 +/- 0.49% in RUPP rats but increased to 11 +/- 3% in RUPP+SA rats. Circulating IL-6 and IL-2 were decreased while IL-10 and TGF-B were significantly increased in RUPP+SA compared to RUPP controls. Vasoactive pathways such as ET-1, AT1-AA, and ROS were all reduced in RUPP+SA compared to RUPP. Pup weight was 2.4 +/- 0.05mg in NP and 1.94 +/- 0.062mg in RUPP and increased to 2.1 +/- 0.05mg in RUPP+SA.ConclusionThese data suggest that stimulating endogenous Tregs lower factors causing hypertension and can improve fetal weight in response to PE.