Placental Regulation of Inflammation and Hypoxia after TNF-α Infusion in Mice

Problem Increased levels of inflammatory cytokines are demonstrated in the serum of women with pre-eclampsia. TNF-alpha infusion in animal models induces proteinuric hypertension similar to human pre-eclampsia. The effect of TNF-alpha on regulation of the immune and hypoxic pathways in the developing placenta and their relationship with experimental pre-eclampsia remains unexamined. Method of Study TNF-alpha was infused into pregnant mice, and the effects on maternal hypertension, proteinuria, circulating levels of sFlt-1 and corresponding placental changes in molecules responding to inflammation (TLR-3 and TLR-4) and hypoxia (HIF-1 alpha) were examined. Results TNF-alpha infusion resulted in maternal hypertension and proteinuria. Molecular changes in the placenta involved upregulation of TLR-3, TLR-4 and HIF-1 alpha. Serum levels of sFlt-1 were high in pregnant animals, but not further upregulated by TNF-alpha infusion. Conclusion A role for maladaptive regulation of TLR and HIF-1 alpha induced by an imbalance in inflammatory cytokines is implicated in the pathogenesis of pre-eclampsia.