1. The role of Interleukin-18 in recurrent early pregnancy loss.
- Author
-
Löb, Sanja, Ochmann, Beate, Ma, Zhi, Vilsmaier, Theresa, Kuhn, Christina, Schmoeckel, Elisa, Herbert, Saskia-Laureen, Kolben, Thomas, Wöckel, Achim, Mahner, Sven, and Jeschke, Udo
- Subjects
- *
RECURRENT miscarriage , *MISCARRIAGE , *INTERLEUKIN-18 , *GENE expression , *IMMUNOSTAINING - Abstract
• 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]
- Published
- 2021
- Full Text
- View/download PDF