Circulating levels of cytokines (IL-6, IL-10 and TGF- β) and CD4+CD25+FOXP3+Treg cell population in recurrent pregnancy loss

Abstract

Recurrent pregnancy loss (RPL), a serious reproductive health issue, characterized by two or more pregnancy losses before 20th week of gestation. Globally, it affects 2-5% couples and the basis of the crisis is still unknown in 50% cases. Successful pregnancy is associated with pro and anti-inflammatory gestational phases that tolerate the semi-allogenic foetus, and disturbance leads to pregnancy complications like RPL. This case-control study aimed to assess the inflammatory status in the mid-gestation of ongoing pregnancy of women with (RPL) and without (NRPL) the history of RPL. Blood samples were processed for PBMC isolation, subjected to Flow-cytometry for CD4⁺CD25⁺FOXP3⁺Treg-cell population count and serum samples for IL-6, TGF-β, IL-10 cytokine levels (ELISA). Significant reduction in the percentage of Treg cells, and elevated values for IL-6/TGF-β and IL-6/IL-10 ratios were observed in RPL over NRPL group (p = 0.0001). Opposing results were seen with respect to the magnitude of history of RPL (2 vs. >2 losses). ROC curve analysis showed the superior discriminatory ability of cytokine ratios (IL-6/TGF-β > IL-6/IL-10) for RPL over Treg cells. Our findings are suggestive of pro-inflammatory dominance in mid-gestation of pregnant women with a history of RPL in general and greater than normal anti-inflammatory milieu in cases with > 2 pregnancy loss. As both sterile and infection related inflammation plays a role in pregnancy loss, studies enrolling women with favourable and unfavourable ongoing pregnancies may shed light on the importance of the present study for developing better management/therapeutic strategies.

Keywords: IL-10; IL-6; ROC; RPL; TGF-β; Treg.