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• Interleukin-18 (IL-18) can induce either Th1 or Th2 immune response depending on the local cytokine environment. • The TaqMan® Human Cytokine Network Array was carried out with placental tissue of patients with healthy pregnancies and recurrent miscarriage in order to investigate differences in IL-18 mRNA expression. • Gene expression analysis revealed a 4,9-times higher expression of IL-18 in recurrent miscarriage patients when compared to the control group.. • IL-18 protein expression was investgated in the placenta of patients with healthy pregnancies, spontaneous and recurrent miscarriage. • A significant upregulation of IL-18 in the decidua was restricted to patients with recurrent miscarriage and therefore might be interesting as a diagnostic marker. A successful pregnancy is a unique and complex immunological state. Cytokines seem to be crucial for the implementation of a tolerogenic environment at the feto-maternal interphase towards the semi-allogenic fetus. Importantly, the switch from a Th1- to a Th2 cytokine profile might play a key role. Interestingly, Interleukin-18 (IL-18) can induce either Th1 or Th2 immune response depending on the local cytokine environment. Therefore, this study investigates the expression of IL-18 in early pregnancy loss. The TaqMan® Human Cytokine Network Array was carried out with placental tissue of patients with healthy pregnancies (n = 15) and recurrent miscarriage (n = 15) in order to investigate differences in IL-18 mRNA expression. Immunohistochemical staining was applied to examine the IL-18 protein expression in the syncytiotrophoblast and decidua of healthy pregnancies (n = 15), spontaneous (n = 12) and recurrent miscarriage (n = 9). The characterization of IL-18 expressing cells in the decidua was evaluated by double-immunofluorescence. Correlation analysis between IL-18 protein expression and clinical data of the study population was performed via spearman correlation coefficient. Gene expression analysis revealed a 4,9-times higher expression of IL-18 in recurrent miscarriage patients. IL-18 protein expression was significantly upregulated only in the decidua in the recurrent miscarriage group (p = 0.031). We did not observe significant changes of IL-18 protein expression in spontaneous miscarriage specimens when compared to healthy controls (p = 0.172). Double-immunofluorescence identified decidual stroma cells as IL-18 expressing cells. Correlation analysis showed a significant negative correlation of IL-18 protein expression and gestational age in healthy controls (r = -,745, p = 0.034). Also, a positive correlation of IL-18 and maternal age was observed in patients suffering from recurrent pregnancy loss (r =, 894, p = 0.041). Our results indicate that IL-18 expression might be necessary in early gestation but requires a tight regulation for a successful ongoing pregnancy. In the present study we observed that a significant upregulation of IL-18 in the decidua was restricted to patients with recurrent miscarriage and therefore might be interesting as a diagnostic marker. Further studies need to evaluate the exact pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

• IL-1β gene expression is 54-times higher in placental tissue of recurrent abortion compared to controls. • Immunohistochemistry confirmed a significant upregulation of IL-1β in the decidua of recurrent miscarriage specimens. • Double-immunofluorescence identified decidual stoma cells as IL-1β expressing cells. • Decidual upregulation of IL-1β may be associated with an imbalanced maternal immune system in early pregnancy loss. Pregnancy is an extraordinarily complex immunological process. For successful pregnancy maintenance the maternal immune system must adapt to and tolerate the semi-allogenic fetus at the fetomaternal interface of the placenta. This balance is regulated by cytokines with a predominant T helper 2 (Th-2) system and a suppressed inflammatory T helper 1 (Th-1) response. This study investigates the role of the Th-1 pro-inflammatory cytokine Interleukin-1 beta (IL-1β) and its role in early pregnancy loss. In order to identify differences in IL- β levels a TaqMan® Human Cytokine Network Array, with placental tissue obtained from patients with healthy pregnancies (n = 15) and recurrent miscarriage (n = 15), was carried out. Protein expression of IL-1 β in the decidua of healthy pregnancies (n = 15), spontaneous (n = 18) and recurrent miscarriages (n = 15), was investigated by immunohistochemistry. The identification of IL-1 β expressing cells in the decidua was done with double-immunofluorescence. Gene expression analysis identified a nearly 54-times higher expression of IL-1 β in placental tissue of patients suffering from recurrent abortion. Immunohistochemistry confirmed a significant upregulation of IL-1 β in the decidua of recurrent miscarriage specimens (p = 0.01) as well as in the decidua of women with spontaneous abortion (p = 0.001). Double-immunofluorescence identified decidual stoma cells as IL-1 β expressing cells. Significant upregulation of IL-1β may be associated with an imbalanced immune system and a procoagulant state that could be responsible for early pregnancy loss. These results provide new evidence of the complex interplay of IL-1β at the fetomaternal interface and its crucial role in miscarriage processes. [ABSTRACT FROM AUTHOR]