PMID- 34627076 OWN - NLM STAT- MEDLINE DCOM- 20220328 LR - 20220328 IS - 1872-7603 (Electronic) IS - 0165-0378 (Linking) VI - 148 DP - 2021 Nov TI - The role of Interleukin-18 in recurrent early pregnancy loss. PG - 103432 LID - S0165-0378(21)00162-5 [pii] LID - 10.1016/j.jri.2021.103432 [doi] AB - BACKGROUND: 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. PATIENTS AND METHODS: The TaqMan(R) 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. RESULTS: 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). CONCLUSION: 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. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Lob, Sanja AU - Lob S AD - Department of Obstetrics and Gynecology, University Hospital, University of Wuerzburg, Josef-Schneider-Str. 4, 97080, Wurzburg, Germany. FAU - Ochmann, Beate AU - Ochmann B AD - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. FAU - Ma, Zhi AU - Ma Z AD - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. FAU - Vilsmaier, Theresa AU - Vilsmaier T AD - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. FAU - Kuhn, Christina AU - Kuhn C AD - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany; Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstrasse 2, 86156, Augsburg, Germany. FAU - Schmoeckel, Elisa AU - Schmoeckel E AD - Department of Pathology, LMU Munich, Marchioninistr. 27, 81377, Munich, Germany. FAU - Herbert, Saskia-Laureen AU - Herbert SL AD - Department of Obstetrics and Gynecology, University Hospital, University of Wuerzburg, Josef-Schneider-Str. 4, 97080, Wurzburg, Germany. FAU - Kolben, Thomas AU - Kolben T AD - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. FAU - Wockel, Achim AU - Wockel A AD - Department of Obstetrics and Gynecology, University Hospital, University of Wuerzburg, Josef-Schneider-Str. 4, 97080, Wurzburg, Germany. FAU - Mahner, Sven AU - Mahner S AD - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. FAU - Jeschke, Udo AU - Jeschke U AD - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany; Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstrasse 2, 86156, Augsburg, Germany. Electronic address: udo.jeschke@med.uni-muenchen.de. LA - eng PT - Journal Article DEP - 20211005 PL - Ireland TA - J Reprod Immunol JT - Journal of reproductive immunology JID - 8001906 RN - 0 (Biomarkers) RN - 0 (Interleukin-18) SB - IM MH - Abortion, Habitual/*immunology MH - Adult MH - Biomarkers/*metabolism MH - Decidua/*immunology MH - Female MH - Humans MH - Interleukin-18/genetics/*metabolism MH - Placenta/*immunology MH - Pregnancy MH - Pregnancy Trimester, First MH - Up-Regulation MH - Young Adult OTO - NOTNLM OT - First trimester placenta OT - Interleukin-18 OT - Recurrent miscarriage OT - Spontaneous miscarriage EDAT- 2021/10/10 06:00 MHDA- 2022/03/29 06:00 CRDT- 2021/10/09 20:28 PHST- 2021/05/11 00:00 [received] PHST- 2021/09/11 00:00 [revised] PHST- 2021/10/01 00:00 [accepted] PHST- 2021/10/10 06:00 [pubmed] PHST- 2022/03/29 06:00 [medline] PHST- 2021/10/09 20:28 [entrez] AID - S0165-0378(21)00162-5 [pii] AID - 10.1016/j.jri.2021.103432 [doi] PST - ppublish SO - J Reprod Immunol. 2021 Nov;148:103432. doi: 10.1016/j.jri.2021.103432. Epub 2021 Oct 5.