Endothelial cell activation by tumour necrosis factor‐alpha (TNF‐α and the development of pre‐eclampsia

SUMMARY Pre‐eclampsia may develop as a result of an endothelial activation. Tumour necrosis factor‐alpha (TNF‐α) 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‐α‐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‐α was below the immunoassay limit of detection (< 80 pg/ml). Five had further samples taken after pre‐eclampsia was clinically diagnosed and, initially, TNF‐α 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‐α was detected in only two (80 and 650 pg/ml). TNF‐α 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‐α levels measured by immunoassay can be elevated in approximately 36% of cases of established preeclampsia, but this rise occurs only after the syndrome is detected clinically. Blood concentrations of TNF‐α and soluble E‐selectin are not related to severity of the disorder. These findings suggest that circulating TNF‐α 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.