Expression of inflammatory cytokines in placentas from women with preeclampsia

It is postulated that inadequate remodeling of the uterine spiral arteries in preeclampsia leads to focal ischemia and generation of inflammatory cyto kines, 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 bet a, and IL-6 levels in placentas from patients with preeclampsia and normal term pregnancies. Because the placenta is a large heterogeneous organ, we a nalyzed multiple sites per placenta. On the average, there was a 3-fold var iation 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 preecla mpsia. There were also no significant differences in TNF alpha messenger ri bonucleic acid between the normal term and preeclamptic placentas, although TNF alpha messenger ribonucleic acid levels were lower in placentas from p reterm patients without diagnosis of preeclampsia than in the normal term p lacentas. In vitro, hypoxia stimulated the production of TNF alpha, IL-1 al pha 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. Fin ally, although peripheral and uterine venous levels of TNF alpha were eleva ted in preeclamptic women compared with normal term patients, the ratio of uterine to peripheral venous TNF alpha levels was not significantly differe nt from 1.0 for either patient group. Taken together, these results suggest that sources other than the placenta contribute to the elevated concentrat ions of TNF alpha and IL-6 found in the circulation of preeclamptic women.