Increased leukocyte adhesion to vascular endothelium in preeclampsia is inhibited by antioxidants.

OBJECTIVE: To test the hypothesis that plasma from women with preeclampsia increases leukocyte adhesion to vascular endothelial cells and that antioxidants inhibit this effect. STUDY DESIGN: Plasma from 12 women with severe preeclampsia and 12 with normal pregnancy was tested in an in vitro leukocyte-endothelium adhesion assay in the presence or absence of vitamin E, vitamin C, or N-acetylcysteine. RESULTS: Preeclamptic plasma significantly increased monocyte (U937 cells) and T-cell (Jurkat) adhesion to human umbilical vein (HUVEC) and microvascular endothelial cells, compared with normal pregnant plasma. The antioxidants vitamin E, vitamin C, and N-acetylcysteine significantly inhibited monocyte adhesion to HUVEC in the presence of preeclamptic but not normal pregnant plasma. Increased adhesion in response to preeclamptic plasma was not mediated through a protein kinase C (PKC) mechanism, because the PKC inhibitor bisindolylmaleimide I had no effect on adhesion in the presence of preeclamptic plasma. CONCLUSION: Severe preeclampsia is associated with increased leukocyte-endothelium adhesion and clinically useful antioxidants can inhibit this effect.

Increased vascular endothelial cell production of interleukin-6 in severe preeclampsia.

OBJECTIVE: The purpose of this study was to determine whether plasma from women with severe preeclampsia stimulates the production of endothelial cell interleukin-6 production and whether vitamin E could inhibit this process. STUDY DESIGN: Human umbilical vein endothelial cells were cultured in the presence of 5% plasma from women with severe preeclampsia (n = 12) or healthy pregnant women at term (n = 12), with or without 50 micromol/L vitamin E. Levels of interleukin-6 in plasma and human umbilical vein endothelial cell-conditioned media were measured by enzyme-linked immunosorbent assay. RESULTS: Interleukin-6 levels were elevated 5-fold in preeclamptic plasma compared with normal pregnant plasma (P <.05). Human umbilical vein endothelial cell interleukin-6 production was increased 25% by preeclamptic plasma compared with normal pregnant plasma (P <.005), and increased interleukin-6 production by preeclamptic plasma was inhibited by vitamin E. CONCLUSION: Endothelial cell activation by preeclamptic plasma stimulates interleukin-6 production, which is inhibited by vitamin E. These findings provide a potential cellular mechanism for the beneficial effects of antioxidant therapy in preeclampsia.

Increased endothelial monocyte chemoattractant protein-1 and interleukin-8 in preeclampsia.

OBJECTIVE: To test the hypothesis that preeclampsia is associated with increased endothelial cell chemokine production of monocyte chemoattractant protein-1 and interleukin-8 necessary for monocyte recruitment to the vascular endothelium. METHODS: Plasma was collected from women with severe preeclampsia and normal pregnant women at term and measured for monocyte chemoattractant protein-1, interleukin-8, and lipid peroxide levels by enzyme-linked immunosorbent assays and malondialdehyde assays. Human umbilical vein endothelial cells were cultured with 5% plasma from normal or preeclamptic patients and the media assayed for monocyte chemoattractant protein-1 and interleukin-8 production. RESULTS: In women with severe preeclampsia, plasma levels of monocyte chemoattractant protein-1, interleukin-8, and lipid peroxides were elevated (1.5-fold, 2.5-fold, and 4.5-fold higher, respectively) compared with normal pregnant women. Human umbilical vein endothelial cells cultured with plasma from preeclamptic women significantly increased the production of both monocyte chemoattractant protein-1 (2.3-fold) and interleukin-8 (1.5-fold) compared with plasma from normal pregnant women. Monocyte chemoattractant protein-1 and interleukin-8 production was decreased by the antioxidant vitamin E in human umbilical vein endothelial cells treated with preeclamptic plasma, suggesting that the production of these cytokines may be regulated by signaling mechanisms sensitive to oxidative stress. CONCLUSION: These findings support the hypothesis that circulating factors in the plasma of women with preeclampsia activate endothelial cell monocyte chemoattractant protein-1 and interleukin-8 production, and although not directly examined in this study, may increase monocyte adherence to the vascular endothelium.