Metabolic syndrome mediates proinflammatory responses of inflammatory cells in preeclampsia

To investigate whether metabolic syndrome (MetS) is associated with exacerbation of inflammatory responses in preeclamptic (PE) patients, the dynamic changes of Th17 and Treg cells, monocytes, cytokines, and transcription pattern of inflammasome-related genes were analyzed in 35 women with PE suffering from MetS in comparison to 38 PE women without MetS and healthy pregnant women.

Expression of inflammasome-related genes, cytokines, and also TLR4 was measured using real-time PCR. Serum and medium supernatant cytokines levels of PBMCs and serum levels of HMGB1 and Caspase-1 were also evaluated by ELISA. Monocytes, Th17, and Treg cells frequency were also determined by flow cytometry.

PE women with MetS exhibited increased percentage of non-classical and intermediate monocytes and Th17 cells (P = 0.025). Furthermore, decreased Treg cells frequency was also observed in PE women with MetS compared to PE women (P = 0.019). The mRNA expression of inflammasome-related genes (Caspase-1, NLRP3, HMGB1), TLR4, IL-1β, IL-6, IL-17, IL-18, and TNF-α was significantly higher in PE patients with MetS than that of the healthy pregnant individuals (P < 0.0001) and PE patients (P < 0.0001). Serum levels of TGF-β and TNF-α in PE patients with MetS were increased compared to other two groups, while IL-10 levels were significantly reduced. A significant sFlt (P = 0.016), Caspase-1 (P = 0.012), HMGB1 (P = 0.016) upregulation, and VEGF (P = 0.023) downregulation were also observed in the serum of PE women having MetS compared to PE women.

MetS is closely related to the exacerbation of inflammatory reactions in PE. This study indicates that, in order to diminish the systemic features of PE, prior to conceive and start a pregnancy, MetS should be severely considered and managed.