Abstract
Preeclampsia (PE), new onset hypertension, is associated with chronic inflammation, autoantibodies to the AT1 receptor (AT1‐AA) and placental ischemia. Currently, there is no effective treatment for PE except for early delivery, making PE the leading cause for premature births worldwide. Evidence indicates a shift towards proinflammatory NK cell, CD4+TH1 vs CD4+TH2 profile exist in PE and in response to placental ischemia in pregnant rats (RUPP). Therefore, we hypothesized that decreasing cytolytic NK and CD4+ TH1 cells and increasing CD4+TH2 cells would improve blood pressure during pregnancy. To do so we infused IL‐4, an anti‐inflammatory cytokine strongly associated with the proliferation of TH2 cells, in to normal pregnant (NP) and RUPP rats. Interleukin‐4, 600 ng/day, was administered via a mini‐osmotic pump on day 14 of gestation, carotid catheters were inserted on gestation day 18, and blood pressure (MAP), AT1‐AA, NK cells, TH2 and B cells were measured on GD 19. MAP in NP rats (n=10) was 96 ± 2, 101 ± 2 in NP+IL‐4 rats (n=14), 130 ± 4 in RUPP rats (n=6), and 108 ± 2 mmHg in RUPP+IL‐4 rats (n=15), p< 0.05. Circulating TH2 cells were 17 ± 3 in NP rats (n=3), 9.0 ± 2.0 in RUPP rats (n=5), but improved to 13 ± 3 % gated in RUPP+IL‐4 rats (n=9). Total placental NK cells were 0.7±0.1 in NP rats (n=4), 0.7±0.3 in NP+IL‐4 rats (n=7), 5.0 ±2 in RUPP rats (n=3) which significantly decreased to 1.6±4 in RUPP±IL‐4 rats (n=7), p<0.05. Placental cytolytic NK cells were 6±2 % in RUPP rats but reduced significantly to 2±0.8 in RUPP+IL‐4 rats. Importantly, circulating B cells were 2.5±0.3 in NP rats (n=3), which increased to 7.5±2 in RUPP rats (n=4) and reduced to 1.4±0.5 in RUPP+IL‐4 rats (n=3). Similarly, AT1‐AA were 0.3±0.4 in NP rats (n=8), 18±0.3 in RUPP rats (n=9), and were blunted to 4±1 bpm in RUPP+IL‐4 rats (n=14), p<0.05. This study illustrates the importance of a balanced CD4+ TH1/TH2, B and NK cell profile during pregnancy and that this can be achieved by administration of IL‐4, which ultimately improved hypertension in response to placental ischemia during pregnancy.Support or Funding InformationNIH grants R01HD067541‐06, T32HL105324This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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