Role of the Macrophage Migration Inhibitory Factor in the Pathophysiology of Pre-Eclampsia

Abstract

Proinflammatory cytokines are produced in pregnancy in response to the invading pathogens and/or nonmicrobial causes such as damage-associated molecules and embryonic semi-allogenic antigens. While inflammation is essential for a successful pregnancy, an excessive inflammatory response is implicated in several pathologies including pre-eclampsia (PE). This review focuses on the proinflammatory cytokine macrophage migration inhibitory factor (MIF), a critical regulator of the innate immune response and a major player of processes allowing normal placental development. PE is a severe pregnancy-related syndrome characterized by exaggerated inflammatory response and generalized endothelial damage. In some cases, usually of early onset, it originates from a maldevelopment of the placenta, and is associated with intrauterine growth restriction (IUGR) (placental PE). In other cases, usually of late onset, pre-pregnancy maternal diseases represent risk factors for the development of the disease (maternal PE). Available data suggest that low MIF production in early pregnancy could contribute to the abnormal placentation. The resulting placental hypoxia in later pregnancy could produce high release of MIF in maternal serum typical of placental PE. More studies are needed to understand the role of MIF, if any, in maternal PE.

Keywords: cytokines; human pregnancy; inflammatory response; placenta.

Figure 1

An inflammatory response is essential in pregnancy to protect against infection, repair tissue injury, and promote a tolerogenic milieu for the fetus. An exacerbated inflammatory response can be harmful for pregnancy outcomes causing diseases such as PE.

Figure 2

Potential role of MIF in the pathogenesis of placental pre-eclampsia. Low MIF production in early pregnancy would contribute to the abnormal placentation with subsequent placenta hypoxia and increased production of proinflammatory cytokines, placental debris, and oxidative stress leading to pre-eclampsia.