Placental Cytokines in the Pathogenesis of Preeclampsia and Hellp Syndrome

Preeclampsia and HELLP syndrome are placenta-dependent disorders with both local and systemic anomalies that are responsible for neonatal and maternal morbidity. The cytokines, produced by the placenta in response to local ischemia/hypoxia, may be involved in endothelial activation and dysfunction. The adaptive immune system could play a key role in the etiology of preeclampsia or HELLP by generating a proinflammatory Th1 type immune reaction: the current pathophysiologic hypothesis of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Also human decidual NK cells recruited at the site of embryonic implantation induce a number of cytokines with potential functions not yet clearly established. We reviewed recent studies on effect of pro-inflammatory cytokines in preeclampsia, as well as on the role of regulatory cytokines and chemokines and discuss evidence that cytokines continue to be part of a paracrine/autocrine regulatory network in the placenta and membranes throughout the different stages of gestation. In addition we reviewed the experimental basis for the possible role of the immune system and proposed the hypothesis that these conditions could be a placental inflammatory response which can lead to a systemic and endothelial dysfunction, resulting in hypertension, proteinuria and pathologies in many organ systems.