Expression of Inflammatory Cytokines in Placentas from Women with Preeclampsia¹

Abstract

It is postulated that inadequate remodeling of the uterine spiral arteries in preeclampsia leads to focal ischemia and generation of inflammatory cytokines, such as tumor necrosis factor (TNF alpha) and interleukins (ILs), by the placenta. Our objective was to compare TNF alpha, IL-1 alpha, IL-1 beta, and IL-6 levels in placentas from patients with preeclampsia and normal term pregnancies. Because the placenta is a large heterogeneous organ, we analyzed multiple sites per placenta. On the average, there was a 3-fold variation in cytokine protein levels across the eight sites analyzed for each placenta. However, there were no significant overall differences among the normal term, preeclamptic, and preterm placentas from women without preeclampsia. There were also no significant differences in TNF alpha messenger ribonucleic acid between the normal term and preeclamptic placentas, although TNF alpha messenger ribonucleic acid levels were lower in placentas from preterm patients without diagnosis of preeclampsia than in the normal term placentas. In vitro, hypoxia stimulated the production of TNF alpha, IL-1 alpha and IL-1 beta, but not that of IL-6, by placental villous explants from both groups of patients, and this was not exaggerated in preeclampsia. Finally, although peripheral and uterine venous levels of TNF alpha were elevated in preeclamptic women compared with normal term patients, the ratio of uterine to peripheral venous TNF alpha levels was not significantly different from 1.0 for either patient group. Taken together, these results suggest that sources other than the placenta contribute to the elevated concentrations of TNF alpha and IL-6 found in the circulation of preeclamptic women.

Tumor Necrosis Factor-Alpha Polymorphism at Position -238 in Preeclampsia

“…A meta-analysis of 24 studies has shown that the level of TNF-α in the maternal plasma is higher in preeclamptic women (13). However there has been no difference in placental tissue levels and TNF-α expression between preeclamptic and normal placenta (14-17); a finding that may point to the maternal origin of higher TNF-α. Several in Vitro and animal studies also support and clarify the role of TNF-α in preeclampsia.…”

Expression of VEGF and VEGF-R3 receptor by placental endothelial cells in health and gestosis

“…The concentrations of proangiogenic factors in placental tissues are significantly reduced in gestosis, while the concentrations of antiangiogenic factors are increased. Antiangiogenic factors, such as TNF-α, secreted by placental macrophages, suppress proliferation and migration of EC [1,3]. Presumably, high content of antiangiogenic and proinflammatory factors in supernatants obtained after culturing of placental explants from patients with gestosis was responsible for reduced viability and low expression of VEGF-R3 by EA.hy926 human EC.…”

Pericytes Contribute to Dysfunction in a Human 3D Model of Placental Microvasculature through VEGF‐Ang‐Tie2 Signaling

“…HLFs in coculture seemingly contribute to more proinflammatory signaling, which can be reduced by addition of interleukin-10 (IL-10, an anti-inflammatory cytokine) in our system ( Figure S7, Supporting Information). [46] Given their role in inflammation, [38] and our findings highlighting the significant role of Angiopoietins in EC-pericyte signaling, we again examined Ang1/2 expression to confirm the roles of each respective stromal cell. [44] These results suggest that the interplay of stromal cells has a significant effect on the inflammatory response, which is in line with the observation that inflammatory signaling is often upregulated in placental-derived stromal cells from PE patients.…”