Preeclamptic Women Have Decreased Circulating IL-10 (Interleukin-10) Values at the Time of Preeclampsia Diagnosis

Abstract

A key immunomodulatory cytokine, IL-10 (interleukin-10), has been shown to be dysregulated in preeclampsia, a pregnancy-specific hypertensive disorder, further characterized by multi-system involvement. However, studies have reported inconsistent findings about circulating IL-10 levels in preeclamptic versus normotensive pregnancies. The aim of the present systematic review and meta-analysis was to assess circulating IL-10 levels in preeclamptic and normotensive pregnancies at 2 time points: before, and at the time of preeclampsia diagnosis. PubMED, EMBASE, and Web of Science databases were searched to include all published studies examining circulating IL-10 levels in preeclamptic and normotensive pregnancies. Differences in IL-10 levels were evaluated by standardized mean differences. Of 876 abstracts screened, 56 studies were included in the meta-analysis. Circulating IL-10 levels were not different before the time of active disease (standardized mean differences, −0.01 [95% CI, −0.11 to 0.08]; P =0.76). At the time of active disease, women with preeclampsia (n=1599) had significantly lower IL-10 levels compared with normotensive controls (n=1998; standardized mean differences, −0.79 [95% CI, −1.22 to −0.35]; P =0.0004). IL-10 levels were lower in both early/severe and late/mild forms of preeclampsia. Subgroup analysis revealed that IL-10 measurement methodology (ELISA or multiplex bead array) and the sample type (plasma or serum) significantly influenced the observed differences, with the use of sera paired with ELISA technology providing the best distinction in IL-10 levels between preeclamptic and normotensive pregnancies. These findings support the role of decreased IL-10 levels in the pathophysiology of preeclampsia. Future studies should address the therapeutic potential of IL-10 in preeclampsia.

SARS-CoV-2 and the Immune Response in Pregnancy with Delta Variant Considerations

“…Increased levels of inflammatory signals such as IL-6, TNF-α, IL-8, CXCL10, CCL2, and CXCL9 were also observed in those severely pre-eclamptic [ 41 ]. Another meta-analysis concluded that there are significantly decreased IL-10 levels observed in those with pre-eclampsia at the time of diagnosis [ 42 ]. As previously discussed, resolution from SARS-CoV-2 infection requires the reduction of inflammatory signals such as IL-6 and TNF-α by protective mediators such as regulatory T cells (Treg) and IL-10.…”

Defective Uteroplacental Vascular Remodeling in Preeclampsia: Key Molecular Factors Leading to Long Term Cardiovascular Disease

“…A recent meta-analysis of 56 studies on the circulating IL-10 levels in preeclamptic women revealed that the serum IL-10 levels were not significantly different before the onset of preeclampsia; however, once the clinical syndrome of preeclampsia occurs, IL-10 levels were significantly lower in preeclamptic women compared to normotensive controls (standardized mean differences, −0.79 [95% CI, −1.22 to −0.35]; p = 0.0004). Moreover, the decreased level of IL-10 was present in all forms of preeclampsia regardless of its onset and severity [ 35 ]. This suggests that IL-10 levels may not be a suitable marker for early detection of preeclampsia, but increasing IL-10 may be a potential therapeutic target of preeclampsia, which could lead to future studies.…”

The human placenta shapes the phenotype of decidual macrophages

“…The latter two in particular, have been shown to exert crucial functions during pregnancy for instance by inducing a decidual-like phenotype in monocyte-derived macrophages (26–28) thereby acting in an autocrine self-perpetuating manner. Furthermore, reduced IL-10 blood levels are associated with human pregnancy disorders such as preeclampsia (29) and while administration of IL-10 prevents naturally occurring fetal losses (30), its deletion can provoke spontaneous abortions in mice (31). M-CSF has been shown to support placental function by affecting EVT invasion (32).…”

“…In particular, the latter two exert critical functions during pregnancy, for example, by inducing a decidual phenotype in monocyte-derived macrophages (Lindau et al, 2021; Svensson-Arvelund et al, 2015; Svensson et al, 2011) thereby acting in an autocrine self-perpetuating manner. Furthermore, reduced IL-10 blood levels are associated with human pregnancy disorders such as preeclampsia (Nath et al, 2020). While administration of IL-10 prevents naturally occurring fetal losses (Chaouat et al, 1995), its deletion can provoke spontaneous abortions in mice (Murphy et al, 2005).…”