Immunomodulatory role of vitamin D in the pathogenesis of preeclampsia

Abstract

Worldwide, preeclampsia is a significant health risk to both pregnant women and their unborn children. Despite scientific advances, the exact pathogenesis of preeclampsia is not yet fully understood. Meanwhile, the incidence of preeclampsia is expected to increase. A series of potential etiologies for preeclampsia has been identified, including endothelial dysfunction, immunological dysregulation and trophoblastic invasion. In this literature review, we have critically reviewed existing literature regarding the research findings that link the role of vitamin D to the pathogenesis and immunoregulation of preeclampsia. The relationship of vitamin D with the suspected etiologies of preeclampsia underscores its clinical potential in the diagnosis and treatment of preeclampsia.

Keywords:

• cathelicidin
• endothelial dysfunction
• immunomodulation
• preeclampsia
• vitamin D

Financial & competing interest’s disclosure

The authors were supported by research grants R01 HL106042, R01 HL112597, and R01 HL120659 to DK Agrawal from the Office of the Director of National Institutes of Health and the National Heart Lung and Blood Institute, NIH, USA. The content of this review is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Further randomized controlled trials using vitamin D supplementation pregnant women is needed to establish a link between preeclampsia and vitamin D.

• Preeclampsia continues to be a major cause of maternal and fetal morbidity and mortality worldwide.

• Although the precise pathophysiology of preeclampsia has not been established, it is thought to occur due to a combination of endothelial cell dysfunction, immune dysfunction and insufficient or reduced trophoblastic invasion.

• Vitamin D has been shown to improve angiogenesis, and some research suggests that low serum vitamin D may contribute to endothelial cell dysfunction.

• Vitamin D has been shown to act as an immune modulator, and there are vitamin D receptors found on almost all immune cells.

• Vitamin D increases IL-10 production and decreases IL-6 production. Increased levels of IL-6 have been associated with preeclampsia, and decreased levels of IL-10 have also been associated with the disease.

• A deficiency in vitamin D causes a decrease in the expression of IL-10 and an increased expression of Th1-mediated proinflammatory cytokines such as IFN-γ, IL-2 and TNF-α. This closely resembles the cytokine changes that take place due to insufficient or reduced trophoblastic invasion. This observation gives one possible explanation as to how a vitamin D deficiency leads to the development of preeclampsia.

• The role of vitamin D in changing calcium absorption may also play a role in the pathogenesis of preeclampsia.

Notes