Pre-eclampsia with inflammatory and pro-resolving mediator fluctuations - contributions from hemolytic protozoan parasites.

Abstract

Pre-eclampsia (PE) and eclampsia are inflammatory hypertension diseases which have caused millions of global fatalities among pregnant women, and their pathogenesis has been a centuries-long mystery. Substantial experimental evidence, including extensive cytokine signatures, symptoms, characteristics and drug interactions, suggest initiation by hemolytic protozoan parasite infections which provide heme and iron for reactivation of iron-deprived bacterial and/or viral infections. However, there are unexplained PE and eclampsia secondary characteristics: (1) Why are endothelial dysfunction and vascular inflammation ubiquitous in pregnancies complicated by PE and eclampsia? (2) Why does pregnancy termination resolve the inflammation of pregnancies complicated by PE and eclampsia? (3) Why do omega-3 polyunsaturated fatty acids, including DHA and EFA and their derived resolvins, have decreased blood levels, whereas omega-6 polyunsaturated fatty acids have elevated levels? (4) Why is low-dose aspirin therapy frequently effective in preventing PE and eclampsia? There are now plausible explanations for these secondary characteristics. These explanations also support the hypothesis that PE and eclampsia are diseases induced by bacterial or viral infections concurrent with a hemolytic protozoan parasite infection, with reactivated infections inducing chronic inflammation. This also causes abnormal fluctuations in special pro-resolving mediators, including lipoxins, resolvins, protectins and maresins, which would normally participate in resolving acute inflammations.