The Serotonin-Immune Axis in Preeclampsia

Curr Hypertens Rep. 2021 Aug 5;23(7):37. doi: 10.1007/s11906-021-01155-4.

Abstract

Purpose of review: To review the literature and detail the potential immune mechanisms by which hyperserotonemia may drive pro-inflammation in preeclampsia and to provide insights into potential avenues for therapeutic discovery.

Recent findings: Preeclampsia is a severe hypertensive complication of pregnancy associated with significant maternal and fetal risk. Though it lacks any effective treatment aside from delivery of the fetus and placenta, recent work suggests that targeting serotonin systems may be one effective therapeutic avenue. Serotonin dysregulation underlies multiple domains of physiologic dysfunction in preeclampsia, including vascular hyporeactivity and excess platelet aggregation. Broadly, serotonin is increased across maternal and placental domains, driven by decreased catabolism and increased availability of tryptophan precursor. Pro-inflammation, another hallmark of the disease, may drive hyperserotonemia in preeclampsia. Interactions between immunologic dysfunction and hyperserotonemia in preeclampsia depend on multiple mechanisms, which we discuss in the present review. These include altered immune cell, kynurenine pathway metabolism, and aberrant cytokine production mechanisms, which we detail. Future work may leverage animal and in vitro models to reveal serotonin targets in the context of preeclampsia's immune biology, and ultimately to mitigate vascular and platelet dysfunction in the disease. Hyperserotonemia in preeclampsia drives pro-inflammation via metabolic, immune cell, and cytokine-based mechanisms. These immune mechanisms may be targeted to treat vascular and platelet endophenotypes in preeclampsia.

Keywords: Immunology; Inflammation; Obstetrics; Preeclampsia; Pregnancy; Serotonin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Female
  • Humans
  • Hypertension*
  • Inflammation
  • Placenta
  • Pre-Eclampsia*
  • Pregnancy
  • Serotonin

Substances

  • Serotonin