title: Circulating cytokines and alarmins associated with placental inflammation in high-risk pregnancies.
abstract: OBJECTIVE
  Inflammation during pregnancy has devastating consequences for the placenta and fetus. These events are incompletely understood, thereby hampering screening and treatment.
  
  
  METHODS
  The inflammatory profile of villous tissue was studied in pregnancies at high-risk of placental dysfunction and compared to uncomplicated pregnancies. The systemic inflammatory profile was assessed in matched maternal serum samples in cases of reduced fetal movements (RFM).
  
  
  RESULTS
  Placentas from RFM pregnancies had a unique inflammatory profile characterized by increased interleukin (IL)-1 receptor antagonist and decreased IL-10 expression, concomitant with increased numbers of placental macrophages. This aberrant cytokine profile was evident in maternal serum in RFM, as were increased levels of alarmins (uric acid, HMGB1, cell-free fetal DNA).
  
  
  CONCLUSIONS
  This distinct inflammatory profile at the maternal-fetal interface, mirrored in maternal serum, could represent biomarkers of placental inflammation and could offer novel therapeutic options to protect the placenta and fetus from an adverse maternal environment.
authors.affiliation: Maternal and Fetal Health Research Centre, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospital NHS Foundation Trust, Manchester, UK; Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Girard
authors.forename: Alexander E P
authors.initials: AE
authors.lastname: Heazell
authors.forename: Hayley
authors.initials: H
authors.lastname: Derricott
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Allan
authors.forename: Colin P
authors.initials: CP
authors.lastname: Sibley
authors.forename: Vikki M
authors.initials: VM
authors.lastname: Abrahams
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D024243:HMGB1 Protein / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D053582:Interleukin-1alpha / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008264:Macrophages / Q000276:immunology; D010920:Placenta / Q000276:immunology / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000503:physiopathology; D018566:Pregnancy, High-Risk / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C508609:IL10 protein, human; C508584:IL1A protein, human; C508585:IL1B protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D016753:Interleukin-10
keywords: High-risk pregnancy; inflammation; placental dysfunction; stillbirth