Interleukin-10: a multi-faceted agent of pregnancy

Abstract

It is widely accepted that pregnancy constitutes a unique developmental event. Unprecedented intrauterine actions of angiogenesis, immunity, and neuroendocrine regulation are juxtaposed to mechanisms of senescence that enable fetal growth and protection. The suppressive and regulatory factors that facilitate healthy pregnancy are under investigation. In non-pregnant systems of infection and inflammation, the cytokine interleukin-10 (IL-10) has been widely investigated because of its potential as a key immunosuppressant in response to a multitude of inflammatory events. In the context of pregnancy, IL-10 levels increase markedly in women during early pregnancy and remain elevated well into the third trimester immediately prior to onset of labor. The role of IL-10 during pregnancy as a suppressor of active maternal immunity to allow acceptance of the fetal allograft has been a point of study. Moreover, secretion of IL-10 by a diverse set of maternal and fetal cells has proven to aid in the orchestration of normal processes of pregnancy. Interestingly, some of the more profound findings regarding the actions of IL-10 during pregnancy have manifested from research that focuses on aberrant pregnancy outcomes as a result of inflammation, hormonal imbalances, or gene-environment interactions. This review focuses on the role of IL-10 as a facilitator of successful pregnancy both as an immune suppressive agent and a mediator of cross talk between the placenta and the decidua. Importantly, we discuss investigations on adverse pregnancy conditions to further elucidate the multifarious role of IL-10 at the maternal-fetal interface.

Figure 1. Inflammatory versus anti-inflammatory limbs of gestation

Starting from implantation through term gestation, the interplay of inflammatory and anti-inflammatory 3 × 8 signaling events are central to normal pregnancy outcomes. Here we represent the suppressive nature of IL-10 over the course of human gestation in contrast to the temporal presence of inflammatory signals.

Figure 2. Cellular cross-talk at the maternal-fetal interface and IL-10

Based on recent data we have created a hypothetical model of cross-talk between dendritic cells (DC), trophoblasts, uNK cells, the non-classical MHC I molecule HLA-G and T regulatory cells. Cellular interactions at the maternal-fetal interface are largely unknown, but studies sighted in this review begin to delineate the course of cell-cell regulation over the course of gestation. The main objective of this cellular cross-talk is IL-10 production by uNK cells and T regulatory cells.

Figure 3. A possible role of IL-10 in angiogenesis

This model highlights recent findings from our lab that showcase IL-10 as a growth factor due to its ability to induce trophoblast cells to enhance expression of aquaporin-1 and VEGFs.