Abstract
ObjectivesIL-35 is a novel inhibitory cytokine. In this study, we investigate the serum levels of inhibitory cytokines IL-35, IL-10 and TGF-β in both normal pregnancies and non-pregnant females, and whether IL-35 is associated with the pathogenesis of recurrent spontaneous abortion. We also try to elucidate the relationships of IL-35 with estrogen and alpha-fetoprotein (AFP).MethodsThe levels of IL-35, IL-10, TGF-β, estradiol (E2), unconjugated estriol (uE3) and AFP were analyzed in 120 normal pregnancies, 40 women suffering recurrent spontaneous abortion, 40 postpartum healthy women and 40 non-pregnant women by enzyme-linked immunosorbent assay (ELISA). The correlations between inhibitory cytokines, estrogen and AFP were assessed with the Spearman rank correlation coefficient.ResultsData are expressed as median and percentiles (Q1, Q3).The level of serum IL-35 in normal pregnancies was significantly higher than that in non-pregnant women [333.6 (59.32, 1391) pg/mL vs. 123.9 (8.763, 471.7) pg/mL; P < 0.001]. A significantly higher level of TGF-β was observed in the first trimester only as compared to non-pregnant women [473.4 (398.0, 580.5) pg/mL vs. 379.7 (311.0, 441.3) pg/mL, P < 0.01]. The difference in serum IL-10 level between pregnant women and non-pregnant women was not significant [8.602 (5.854, 12.89) pg/mL vs. 9.339 (5.691, 12.07) pg/mL; P > 0.05]. The level of serum IL-35 in recurrent spontaneous abortion was significantly lower than that in normal early pregnancy [220.4 (4.951, 702.0) pg/mL vs. 386.5 (64.37, 1355) pg/mL; P < 0.05]. The higher IL-35 level in first trimester pregnant women correlated with E2 (r = 0.3062, P < 0.01) and AFP (r = 0.3179, P < 0.01).ConclusionSerum levels of IL-35 increased in normal pregnancy and decreased in recurrent spontaneous abortion. Increased IL-35 correlated with estrogen and AFP levels in early pregnancy. IL-35 is becoming recognized as an active player in the maintenance of a successful pregnancy, but this is not the case for IL-10 or TGF-β.
Highlights
Pregnancy is a major challenge for the maternal immune system
We investigate the serum levels of inhibitory cytokines IL-35, IL-10 and TGF-β in both normal pregnancies and non-pregnant females, and whether IL-35 is associated with the pathogenesis of recurrent spontaneous abortion
Serum levels of IL-35 increased in normal pregnancy and decreased in recurrent spontaneous abortion
Summary
The foreign antigens expressed by the fetus can even stimulate the immune system. In this complex immunological dilemma, the maternal immune system actively responds to fetal antigens with the help of endocrine pathways [1,2]. Regulatory T cells (Treg) play an important role in maintaining immune tolerance, inhibiting progression of autoimmune disease and preventing excessive inflammatory response [3]. Cytokine pathways are considered to be the major mechanism for immunosuppression of Tregs. IL-35 is an inhibitory cytokine first identified in 2007, which is produced primarily by CD4+Foxp3+Treg cells and required for the suppressive activity of regulatory T-cell populations [16,17,18]. IL-35 is produced by activated B cells, tolerogenic dendritic cells and to a lesser extent by activated endothelial cells, smooth muscle cells, and monocytes [19,20,21,22,23]
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