Preeclampsia-Induced T Helper-Associated Cytokine Imbalances Persist Postpartum.

Preeclampsia (PreE), a hypertensive disorder in pregnancy, contributes to long-term maternal cardiovascular disease risk. By 2025, it is estimated that more women than men will have hypertension (HTN), yet the mechanisms contributing to the development of HTN in women are less understood. One potential mechanism underlying HTN in women is a persistent imbalance of anti- and pro- inflammatory T H cells following PreE. Consistent with this, anti-inflammatory T helper (T H ) cytokines are reduced and pro-inflammatory T H cytokines are increased during a PreE pregnancy. De-identified and coded plasma samples and clinical data were obtained from the Magee-Women’s Research Institute & Foundation or the University of Iowa Maternal-Fetal Tissue Bank (IRB 201808705) from women 1-3 (N=93) or 8-10 (N=58) years (yrs) following a normotensive (CTL) or PreE-affected pregnancy. Postpartum (PP) HTN was defined as having stage 1 or higher HTN as designated in the updated 2017 ACC/AHA guidelines. Women with PreE had higher rates of HTN at 1-3 years and at 8-10 years PP, (24% vs. 5% and 65% vs. 17%, all p<0.05) compared to women with a normotensive pregnancy. To determine if T H cells play a role in the future development of HTN, we investigated if the T H cytokine changes observed in PreE persist 1-3 yrs and 8-10 yrs PP. Cytokine concentrations were determined via ELISAs and normalized to total protein. Average cytokine concentrations are reported in pg/g. At 1-3 yrs PP, concentrations of anti-inflammatory cytokines IL-4 (47 vs. 6819, p<0.05), IL-10 (1204 vs. 15042, p<0.05) and TGFβ (8.2x10 5 vs. 4.4x10 6 , p<0.05) were reduced in women with a prior PreE pregnancy vs. women with a CTL pregnancy. At 8-10 yrs PP, pro-inflammatory IL-6 (86 vs. 18, p<0.05) and TNFα (298 vs. 53, p<0.05) were both significantly increased in women with prior PreE compared to women with a CTL pregnancy. Here, we confirm women with a prior PreE pregnancy present with a higher prevalence of HTN early (1-3 yrs) and later (8-10 yrs) PP compared to women with a normotensive pregnancy. Further, we show an altered T H cytokine milieu persists following delivery in women with PreE. This pro-inflammatory milieu is associated with increased rates of HTN and thus, may underlie the future development of HTN in women with a history of PreE.