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Expression of Inflammatory Cytokines in Placentas from Women with Preeclampsia¹

Departments of Obstetrics, Gynecology, and Reproductive Sciences (D.F.B., C.S., K.P.C.) and Cell Biology and Physiology (K.P.C.), University of Pittsburgh School of Medicine, and Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213; and Nuffield Department of Obstetrics and Gynecology, University of Oxford, John Radcliffe Hospital (A.S., C.W.G.R.), Oxford, United Kingdom OX3 9DU

Address all correspondence and requests for reprints to: Dr. Kirk P. Conrad, Magee-Womens Research Institute, 204 Craft Avenue, Pittsburgh, Pennsylvania 15213. E-mail: rsikpc{at}mail.magee.edu

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) and interleukins (ILs), by the placenta. Our objective was to compare TNF, IL-1, IL-1ß, 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 messenger ribonucleic acid between the normal term and preeclamptic placentas, although TNF 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, IL-1 and IL-1ß, 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 were elevated in preeclamptic women compared with normal term patients, the ratio of uterine to peripheral venous TNF 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 and IL-6 found in the circulation of preeclamptic women.

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