Severe preeclampsia goes along with a cytokine network disturbance towards a systemic inflammatory state

Although preeclampsia causes high maternal/fetal morbidity and mortality, the etiology of this multi-system disorder still remains to be elucidated. Herein, we have characterized the cytokine plasma levels in severe preeclamptic women compared to normotensive pregnant and non-pregnant women, aiming to better understand the immunological network and its clinical significance for the pathogenesis and severity of preeclampsia. A total of 219 women were selected. The study population was composed of three groups referred as severe preeclamptic, normotensive pregnant and non-pregnant women. Cytokine plasma levels were determined using commercially available kits, Cytometric Beads Array - CBA to quantify TNF-α, IFN-γ, IL-4, IL-5, IL-10, IL-1β, IL-6, IL-8 and IL-12. Our findings demonstrated that severe preeclamptic state is associated with high levels of pro-inflammatory cytokines IL-8, IL-6, and IFN-γ (P < 0.05 for all) whereas normotensive pregnancy evolves high levels of regulatory cytokine IL-10 (P < 0.05). Moreover, an outstanding pro-inflammatory "cytokine signature" could be observed in severe preeclamptic women display, while an overall regulatory state is the hallmark for normotensive pregnancy. In summary, our data showed that elevated levels of pro-inflammatory cytokines in the maternal circulation with a deviation in the "IL-8 × IL-6" axis towards IFN-γ might drive the cytokine network in preeclamptic women towards an excessive systemic inflammatory state.