title: Endothelial cell activation by tumour necrosis factor-alpha (TNF-alpha) and the development of pre-eclampsia.
abstract: Pre-eclampsia may develop as a result of an endothelial activation. Tumour necrosis factor-alpha (TNF-alpha) activates endothelial cells which release soluble E-selectin, a putative circulating marker specific for endothelial damage. A retrospective longitudinal study of maternal blood samples, collected at different gestational ages in pregnancy, was undertaken to determine whether the development of pre-eclampsia is associated with TNF-alpha-mediated endothelial activation. This study included 19 women who developed pre-eclampsia and 22 women whose pregnancy outcome was normal. Ten women had blood samples taken before pre-eclampsia was clinically detected and, in all these, TNF-alpha was below the immunoassay limit of detection (< 80 pg/ml). Five had further samples taken after pre-eclampsia was clinically diagnosed and, initially, TNF-alpha was still below the lower limit of detection in all five pregnancies, but rose later in three (80, 156 and 250 pg/ml). In nine other patients with diagnosed pre-eclampsia, TNF-alpha was detected in only two (80 and 650 pg/ml). TNF-alpha was identified in only one of the 22 normal pregnancies (80 pg/ml), this being at term. There was no statistical difference in soluble E-selectin levels between normal and pre-eclamptic pregnancies, neither before nor after pre-eclampsia was diagnosed. Hence, blood TNF-alpha levels measured by immunoassay can be elevated in approximately 36% of cases of established pre-eclampsia, but this rise occurs only after the syndrome is detected clinically. Blood concentrations of TNF-alpha and soluble E-selectin are not related to severity of the disorder. These findings suggest that circulating TNF-alpha does not contribute to the initiation of endothelial cell activation that may be associated with the development of pre-eclampsia, but may rise as a consequence of the pathological processes of this disorder.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Liverpool Medical School, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Meekins
authors.forename: P J
authors.initials: PJ
authors.lastname: McLaughlin
authors.forename: D C
authors.initials: DC
authors.lastname: West
authors.forename: I R
authors.initials: IR
authors.lastname: McFadyen
authors.forename: P M
authors.initials: PM
authors.lastname: Johnson
mesh_terms: D015815:Cell Adhesion Molecules / Q000097:blood*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000276:immunology* / Q000503:physiopathology; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha