PMID- 15617632 OWN - NLM STAT- MEDLINE DCOM- 20050201 LR - 20140723 IS - 1064-1955 (Print) IS - 1064-1955 (Linking) VI - 23 IP - 3 DP - 2004 TI - Tumor necrosis factor-alpha in whole blood cultures of preeclamptic patients and healthy pregnant and nonpregnant women. PG - 319-29 AB - OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is recognized as a likely mediator of the excessive endothelial activation and injury that is a key pathogenetic mechanism of preeclampsia. We used whole blood cell cultures from 12 patients with severe preeclampsia and from 12 healthy pregnant and nonpregnant women to determine the release of TNF-alpha by unstimulated leukocytes as a measure of their state of activation, and their response to stimulation with lipopolysaccharide (LPS) as an indicator of their state of priming. METHODS: Blood was cultivated without and with LPS, and TNF-alpha release was measured after six and 24 hours of cultivation by enzyme-linked immunoassays. Differential leukocyte counts were performed, and TNF-alpha values calculated per 10(5) monocytes. RESULTS: In unstimulated whole blood cultures, TNF-alpha release after six hours of cultivation was similar in all three groups; but after 24 hours, TNF-alpha concentrations in culture supernatants from preeclamptic patients were significantly higher than were values obtained in blood from normotensive pregnant women. In LPS-stimulated blood cultures with a maximum of TNF-alpha release at six hours cultivation time, TNF-alpha concentrations were significantly lower in preeclamptic women than they were in both control groups. We showed in an additional experiment that a strong LPS challenge following preactivation with high doses of LPS resulted in reduced release of TNF-alpha compared with release of TNF-alpha following preactivation with low doses of LPS. CONCLUSIONS: The observed high capacity for spontaneous TNF-alpha release by leukocytes in preeclampsia indicates activation of TNF-alpha producing leukocytes by the disease process. Preactivation and exhaustion of leukocytes by leakage of TNF-alpha could lead to the reduced response to TNF-alpha inducer LPS as observed in blood cultures from preeclamptic patients. FAU - Beckmann, Ilse AU - Beckmann I AD - Department of Obstetrics and Gynecology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands. i.dimigen-beckmann@erasmusmc.nl FAU - Efraim, Shlomo Ben AU - Efraim SB FAU - Vervoort, Monica AU - Vervoort M FAU - Visser, Wil AU - Visser W FAU - Wallenburg, Henk C S AU - Wallenburg HC LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Hypertens Pregnancy JT - Hypertension in pregnancy JID - 9421297 RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - C137DTR5RG (Theophylline) RN - ZTY15D026H (bamifylline) SB - IM MH - Adult MH - Endothelium, Vascular/physiopathology MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Humans MH - Leukocyte Count MH - Leukocytes/metabolism MH - Lipopolysaccharides MH - Pre-Eclampsia/*blood MH - Pregnancy MH - Theophylline/*analogs & derivatives MH - Tumor Necrosis Factor-alpha/*analysis EDAT- 2004/12/25 09:00 MHDA- 2005/02/03 09:00 CRDT- 2004/12/25 09:00 PHST- 2004/12/25 09:00 [pubmed] PHST- 2005/02/03 09:00 [medline] PHST- 2004/12/25 09:00 [entrez] AID - 200030334 [pii] AID - 10.1081/PRG-200030334 [doi] PST - ppublish SO - Hypertens Pregnancy. 2004;23(3):319-29. doi: 10.1081/PRG-200030334.