title: Elevated Serum Level of IL-35 Associated with the Maintenance of Maternal-Fetal Immune Tolerance in Normal Pregnancy.
abstract: OBJECTIVE
  IL-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).
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Data 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).
  
  
  CONCLUSIONS
  Serum 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.
authors.affiliation: Department of Laboratory Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
authors.forename: Chao-yan
authors.initials: CY
authors.lastname: Yue
authors.affiliation: Department of Laboratory Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Ying
mesh_terms: D000022:Abortion, Spontaneous / Q000097:blood / Q000276:immunology; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000097:blood; D007378:Interleukins / Q000097:blood*; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000097:blood; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D004967:Estrogens; C508609:IL10 protein, human; D007378:Interleukins; D016212:Transforming Growth Factor beta; D000509:alpha-Fetoproteins; C532417:interleukin-35, human; D016753:Interleukin-10