title: Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia.
abstract: Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/β/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Southcombe
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: C W G
authors.initials: CW
authors.lastname: Redman
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: I L
authors.initials: IL
authors.lastname: Sargent
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: I
authors.initials: I
authors.lastname: Granne
mesh_terms: D000328:Adult; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism*; D053577:Interleukin-1 Receptor Accessory Protein / Q000097:blood / Q000378:metabolism; D007378:Interleukins / Q000097:blood / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D020298:U937 Cells
chemical_list: D016207:Cytokines; C571243:IL-38 protein, human; C508587:IL37 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D007378:Interleukins; C118370:interleukin-18 binding protein
keywords: IL-1 superfamily; cytokines; pre-eclampsia; pregnancy