{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T17:31:32Z","timestamp":1790530292952,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,6,29]],"date-time":"2015-06-29T00:00:00Z","timestamp":1435536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000325","name":"Wellbeing of Women","doi-asserted-by":"publisher","award":["RG1326"],"award-info":[{"award-number":["RG1326"]}],"id":[{"id":"10.13039\/501100000325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,13]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>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-36\u03b1\/\u03b2\/\u03b3\/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.<\/jats:p>","DOI":"10.1111\/cei.12608","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T16:44:48Z","timestamp":1424277888000},"page":"480-490","source":"Crossref","is-referenced-by-count":63,"title":["Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia"],"prefix":"10.1093","volume":"181","author":[{"given":"J H","family":"Southcombe","sequence":"first","affiliation":[{"name":"Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C W G","family":"Redman","sequence":"additional","affiliation":[{"name":"Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I L","family":"Sargent","sequence":"additional","affiliation":[{"name":"Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Granne","sequence":"additional","affiliation":[{"name":"Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, 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