TNF-α-driven immune imbalance in preeclampsia: The role of TNFR1/TNFR2 in monocyte subsets.

Preeclampsia (PE) is a pregnancy-specific syndrome characterized by an intense systemic inflammatory response and monocyte activation, with increased production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α). Evaluation of TNF-α receptor expression (TNFR1 and TNFR2) in monocyte subpopulations may provide new insights into the inflammatory mechanisms underlying this syndrome. In this study, monocytes from 20 women with PE and 20 normotensive (NT) pregnant women were analyzed by flow cytometry for M1-like (TLR4, CD64) and M2-like (CD163, CD206) markers, as well as TNFR1 and TNFR2 expression. Plasma levels of TNF-α, interleukin (IL)-1β, transforming growth factor beta (TGF-β), IL-10; and the soluble forms of TNF-α receptors, sTNFR1 and sTNFR2, were measured by ELISA. Monocytes from women with PE exhibited increased expression of TLR4 and CD64 and reduced expression of CD163 and CD206 compared with the NT group. In addition, a higher percentage of both M1-like and M2-like monocytes expressing TNFR1 and TNFR2 were observed in PE. Plasma concentrations of TNF-α, IL-1β, TGF-β, and sTNFR1 were significantly increased, whereas IL-10 levels were reduced in women with PE. No significant differences were observed in sTNFR2 levels between groups. These findings indicate that PE is associated with a predominance of M1-like monocytes and a reduction in the M2-like phenotype, contributing to the systemic inflammatory state characteristic of the syndrome. This imbalance appears to be linked to enhanced activation of the TNF-α/TNFR1 axis and dysregulated TNFR2-mediated regulatory signaling, highlighting TNF-α-driven immune dysregulation as a potential contributor to PE pathophysiology.