Effect of hypoxia, oxidative stress and lipopolysaccharides on the releaseof prostaglandins and cytokines from human term placental explants

Placental hypoxia, ischaemia, reperfusion and resultant oxidative stress, w ith the release of various factors into the maternal vasculature acting as mediators of endothelial cell dysfunction, play an important role in the de velopment of pre-eclampsia. Human term placental tissue explants were exposed to different stressors, e .g. hypoxia, oxidative stress and lipopolysaccarides, and the effect on the release of prostanoids and cytokines was determined. The hypoxic environme nt consisted of 2 per cent O-2, 5 per cent CO2 and 93 per cent N-2. Oxidati ve stress was induced by addition of xanthine together with xanthine oxidas e to the incubation medium. As a third experimental variable, lipopolysacch aride was added to the medium. Prostaglandins (8-iso-PGF(2 alpha), or 6-ket o-PGF(1 alpha) and TXB2 as stable metabolites of prostacyclin and thromboxa ne, respectively) and cytokines (TNF-alpha, IL-1 alpha, IL-1 beta, IL-6) we re measured using commercial ELISA assays. Under control conditions, the production of prostaglandins in ng/24 h (mean +/- s.d.) was 6 +/- 3 for 8-iso-PGF(2 alpha), 19 +/- 9 for 6-keto-PGF(1 al pha) and 5 +/- 2 for TXB2. The production of cytokines was 13 +/- 6 pg for TNF-alpha, 7 +/- 2 pg for IL-alpha, 5 +/- 3 pg for IL-1 beta and 18 +/- 9 n g for IL-6. Under hypoxia the production of prostaglandins remained unchang ed and of the cytokines only IL-1 beta showed a 15-fold increase. Oxidative stress resulted in an increase in the release of prostaglandins and of cyt okines of 4- to 15- and 3- to 130-fold, respectively. Lipopolysaccharides a nd oxidative stress had a similar effect on the production of prostaglandin s, whereas the stimulatory effect of lipopolysaccharides on cytokines was s ignificantly higher than that of oxidative stress. (C) 2001 IFPA and Harcou rt Publishers Ltd.