Maternal Immune System and State of Inflammation Dictate the Fate and Severity of Disease in Preeclampsia

Preeclampsia, a multisystem disorder in pregnant women, is diagnosed by onset of new hypertension, proteinuria, or organ damage. Antiangiogenic factors, such as soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), are long known to be involved in preeclampsia. However, the role of maternal immune system and inflammation in promotion of preeclampsia has lately been a subject of immense interest. Link between maternal inflammation and preeclampsia is not well established. Furthermore, whether cigarette smoke promotes inflammation and also promotes severity of preeclampsia remains an open question. We herein investigated correlation of established inflammation signatures in the plasma and placental tissue from cohorts of preterm preeclampsia (PPE) and preterm pregnancies (control) with or without smoking history. Besides confirming increased levels of Flt1 and Eng in preeclampsia, we also observed an increase in various mediators of maternal inflammation in women with PPE compared to preterm cohort. Increased IL-6, IL-35, and TNF-α and reduced IL-10 in serum and higher MMP-12, TLR4, HMGB-1, and iNOS and lower Foxp3, CD56 transcripts in placental tissues of PPE compared to preterm pregnancies indicate an association of preterm preeclampsia with stark imbalance in maternal immune system and signatures of inflammation. Smoker PPE cohorts showed highest inflammatory signatures including statistically significant increase for many signatures compared to other cohorts. Together, these results provide evidence for association of inflammation with PPE and strong correlation of smoking with inflammatory signatures in PPE.