title: ST2 and IL-33 in pregnancy and pre-eclampsia.
abstract: Normal pregnancy is associated with a mild systemic inflammatory response and an immune bias towards type 2 cytokine production, whereas pre-eclampsia is characterized by a more intense inflammatory response, associated with endothelial dysfunction and a type 1 cytokine dominance. Interleukin (IL)-33 is a newly described member of the IL-1 family, which binds its receptor ST2L to induce type 2 cytokines. A soluble variant of ST2 (sST2) acts as a decoy receptor to regulate the activity of IL-33. In this study circulating IL-33 and sST2 were measured in each trimester of normal pregnancy and in women with pre-eclampsia. While IL-33 did not change throughout normal pregnancy, or between non-pregnant, normal pregnant or pre-eclamptic women, sST2 was significantly altered. sST2 was increased in the third trimester of normal pregnancy (p<0.001) and was further increased in pre-eclampsia (p<0.001). This increase was seen prior to the onset of disease (p<0.01). Pre-eclampsia is a disease caused by placental derived factors, and we show that IL-33 and ST2 can be detected in lysates from both normal and pre-eclampsia placentas. ST2, but not IL-33, was identified on the syncytiotrophoblast layer, whereas IL-33 was expressed on perivascular tissue. In an in vitro placental perfusion model, sST2 was secreted by the placenta into the 'maternal' eluate, and placental explants treated with pro-inflammatory cytokines or subjected to hypoxia/reperfusion injury release more sST2, suggesting the origin of at least some of the increased amounts of circulating sST2 in pre-eclamptic women is the placenta. These results suggest that sST2 may play a significant role in pregnancies complicated by pre-eclampsia and increased sST2 could contribute to the type 1 bias seen in this disorder.
authors.affiliation: Oxford Fertility Unit, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Granne
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Southcombe
authors.forename: James V
authors.initials: JV
authors.lastname: Snider
authors.forename: Dionne S
authors.initials: DS
authors.lastname: Tannetta
authors.forename: Tim
authors.initials: T
authors.lastname: Child
authors.forename: Christopher W G
authors.initials: CW
authors.lastname: Redman
authors.forename: Ian L
authors.initials: IL
authors.lastname: Sargent
mesh_terms: D000328:Adult; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000097:blood* / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D012995:Solubility
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface