Interleukin‐6, turnour necrosis factor and soluble turnour necrosis factor receptors in women with pre‐eclampsia

Abstract

Objectives Generalised maternal endothelial cell dysfunction appears to be an underlying problem in pre‐eclampsia presumed to be caused, directly or indirectly, by one or more circulating factors derived from the placenta. Recently it has been suggested that tumour necrosis factor (TNF) may play an important role in pre‐eclampsia and contribute to endothelial activation. This study was designed to investigate this proposal. Design Plasma TNF‐α, IL‐6 and both forms of soluble TNF receptors (p55 and p75 TNF‐R) have been measured by ELISA in 31 pre‐eclamptic patients and 31 pregnant controls matched for age, parity and gestational age. Results Levels of IL‐6, TNF‐α and soluble TNF‐R (p55 and p75) were significantly higher in pre‐eclamptic patients, compared with age and gestation matched controls with a wide variation in levels between pre‐eclamptic individuals. There was a correlation between levels of IL‐6 and TNF or TNF‐R and between TNF and TNF‐R levels. However, when the pre‐eclamptic patients were subdivided on the basis of the severity of their disease, the median values of plasma concentrations of IL‐6, TNF‐α and TNF‐R were all higher in the group with lower platelet counts. Conclusions These new findings are consistent with the concept that the maternal syndrome of pre‐eclampsia is associated with endothelial dysfunction and provide evidence that at least part of this dysfunction could arise from excessive release of TNF‐α into the circulation.

Tumour necrosis factor-alpha (TNF-α) gene polymorphism and expression in pre-eclampsia

“…Nevertheless, there are studies showing increased TNF-activity or level in pre-eclamptic patients [11][12][13]. Finally, although it is unlikely that the difference between the TNF1 and TNF2 alleles found in the pre-eclamptic patients is due to PCR efficiency, further study is needed to exclude this possibility.…”

“…The detection of TNF mRNA expression can overcome this discrepancy and therefore can reflect the true level of TNF-in the circulation. In addition, it has also been reported that measurement of the soluble TNF receptor is a more reliable estimation of excessive TNF-release [13].…”

“…Natural induction of TNF is protective, but its overproduction may have very detrimental effects on the host by direct effects on target cells possessing specific TNF receptors and indirect effects mediated by up-regulation of other cytokines and other inflammatory mediators, such as reactive oxygen species [10]. Recent studies in patients with pre-eclampsia have shown that TNF-levels in the plasma and amniotic fluid are increased in this disorder, and suggest that it plays a role in the development of preeclampsia [11][12][13]. Herein, we report that a quantitative polymerase chain reaction (PCR) analysis shows an increase in TNF-gene expression in patients with pre-eclampsia, and this may be associated with TNF-gene polymorphism.…”

TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

“…Studies in animal models of PIH have proposed that a localized reduction in the uteroplacental perfusion pressure and the ensuing placental ischemia and hypoxia during late pregnancy trigger the release of vasoactive factors from the ischemic placenta into the systemic circulation, and that the released factors in turn cause systemic vascular changes and lead to increased vascular resistance and PIH (3, 7, 11-17, 21, 35, 41, 47). Although several placental factors have been suggested, a key role for plasma cytokines in the pathogenesis of PIH has been hypothesized (12,14,39,66). …”

“…Although several placental factors have been suggested, a key role for plasma cytokines in the pathogenesis of PIH has been hypothesized (12,14,39,66). In support of the "cytokine hypothesis," it has been shown that the plasma levels of tumor necrosis factor-␣ (TNF-␣) are elevated in women with preeclampsia (14,39,66). Also, we have shown that a two-to threefold elevation in plasma TNF-␣ in late-pregnancy rats results in significant increases in systemic vascular resistance and arterial pressure (2,19,27).…”