Circulating concentrations of pro-inflammatory cytokines in preeclampsia with varying disease severity

Background: Preeclampsia affects about 5% of pregnancies and is diagnosed by new onset of hypertension with end-organ dysfunction. It is hypothesized that systemic inflammation causes maternal vascular endothelial dysfunction and vascular injury. Objective: To assess whether plasma concentrations of the circulating inflammatory proteins Interleukin-6 (IL-6), Vascular Cell Adhesion Molecule-1 (VCAM-1) and C-Reactive Protein (CRP) are increased in women with preeclampsia with end-organ complications (severe disease with high morbidity), compared with women with preeclampsia without end-organ complications (hypertension and excessive proteinuria only). Study Design We used samples from a large prospective biobank collection (Preeclampsia Obstetric Adverse Event biobank), and two large, randomized preeclampsia therapeutic treatment trials. All samples were collected in Cape Town, South Africa. The last plasma sample collected prior to birth was analyzed for IL-6, VCAM-1 and CRP concentrations. We categorized cases according to disease severity and compared circulating levels of these analytes. Covariate adjustment was performed for maternal age, body mass index, gestational age and time from sampling to delivery as covariates. Results: Of 183 women we included, 119 had preeclampsia without end-organ complications. The remaining 64 had preeclampsia with severe features: 49 had one end-organ complication and 15 had multiple end-organ complications. Compared with women without end-organ complications, those with preeclampsia with multiple end-organ complications had a 4.9-fold (95% CI, 1.81–13.09, p=0.001) increase in IL-6 and a 1.7-fold (95% CI, 1.11–2.72, p=0.012) increase in VCAM-1 plasma concentrations. Comparing women with multiple end-organ complications to those with one end-organ complication, plasma concentrations of IL-6 were 3.2-fold (95% CI, 1.18–8.39, p=0.018) increased, while there was no statistically significant difference for VCAM-1 (1.2-fold higher, 95% CI, 0.79-1.91, p=0.50). Plasma concentrations of CRP did not differ between the groups. Conclusion: Plasma concentrations of IL-6 and VCAM-1, but not CRP, were increased among women with preeclampsia and end-organ complications, compared with women without end-organ complications. IL-6 and VCAM-1 could be drivers of disease in preeclampsia and potentially useful to identify women at high risk of severe disease.