Increased Release of Tumor Necrosis Factor-alpha and Interleukin-6 in Women with the Syndrome of Hemolysis, Elevated Liver Enzymes, and Low Platelet Count

Background: Complement is activated in preeclampsia and complement products are known to activate macrophages. The aim of this study was to determine whether the macrophage derived cytokines, interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha, are released in patients with a form of severe preeclampsia characterized by the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome).

Methods: Complement activation and plasma levels of cytokines were studied in 11 women with HELLP syndrome and in 11 controls with uncomplicated pregnancies. To further evaluate the connection between complement activation and cytokine release an in vitro study on heparinized whole blood incubated with recombinant C5a was performed.

Results: In the HELLP group, complement anaphylatoxin C5a was increased in plasma at delivery (p < 0.01) and one day after delivery (p < 0.05), terminal C5b-9 complement complex was elevated in plasma at delivery (p < 0.001) and one day after (p < 0.01), plasma levels of interleukin-6 were increased one day after delivery (p < 0.01), and plasma concentrations of tumor necrosis factor-alpha were elevated at delivery (p < 0.01), compared with corresponding levels in controls. All parameters normalized within one week. Interleukin-I beta did not differ between the groups. In vitro, recombinant C5a incubated in whole blood gave a dose-dependent release of interleukin-6. No increased release of interleukin-1 or tumor necrosis factor-alpha was seen after incubation.

Conclusions: Since cytokine release occurs in severe preeclampsia, inflammatory mechanisms may participate in the pathophysiology of severe preeclampsia.