Mechanism of inflammatory mediators in preeclampsia
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Preeclampsia (PE) affects 5–7% of all pregnancies in the U.S. and is the leading cause of maternal and prenatal morbidity. PE is associated with hypertension after week 20 of gestation, decreased renal function, and small-for-gestational-age babies. Women with PE exhibit chronic inflammation and production of autoantibodies. It is hypothesized that during PE, placental ischemia occurs as a result of shallow trophoblast invasion which is associated with an immune imbalance where pro-inflammatory CD4+ T cells are increased and T regulatory cells (Tregs) are decreased. This imbalance leads to chronic inflammation characterized by oxidative stress, pro-inflammatory cytokines, and autoantibodies. Studies conducted in our laboratory have demonstrated the importance of this immune imbalance to cause hypertension in response to placental ischemia in pregnant rats. These studies confirm that increased CD4+ T cells and decreased Tregs during pregnancy leads to elevated inflammatory cytokines, endothelin (ET-1), reactive oxygen species (ROS), and agonistic autoantibodies to the Angiotensin II (Ang II), type 1 receptor (AT1-AA). All of these factors taken together play an important role in increasing the blood pressure during pregnancy. Specifically, this review focuses on the decrease in Tregs, and their associated regulatory cytokine IL-10, which is seen in response to placental ischemia during pregnancy. This study will also examine the effect of regulatory immune cell repopulation on the pathophysiology of preeclampsia. These studies show that restoring the balance of the immune system through increasing Tregs, either by adoptive transfer or by infusing IL-10, reduces the blood pressure and pathophysiology associated with placental ischemia in pregnant rats.