title: IL-1α mediated chorioamnionitis induces depletion of FoxP3+ cells and ileal inflammation in the ovine fetal gut.
abstract: BACKGROUND
  Endotoxin induced chorioamnionitis increases IL-1 and provokes an inflammatory response in the fetal ileum that interferes with intestinal maturation. In the present study, we tested in an ovine chorioamnionitis model whether IL-1 is a major cytokine driving the inflammatory response in the fetal ileum.
  
  
  METHODS
  Sheep bearing singleton fetuses received a single intraamniotic injection of recombinant ovine IL-1α at 7, 3 or 1 d before caesarian delivery at 125 days gestational age (term = 150 days).
  
  
  RESULTS
  3 and 7 d after IL-1α administration, intestinal mRNA levels for IL-4, IL-10, IFN-γ and TNF-α were strongly elevated. Numbers of CD3+ and CD4+ T-lymphocytes and myeloidperoxidase+ cells were increased whereas FoxP3+ T-cells were detected at low frequency. This increased proinflammatory state was associated with ileal mucosal barrier loss as demonstrated by decreased levels of the intestinal fatty acid binding protein and disruption of the tight junctional protein ZO-1.
  
  
  CONCLUSIONS
  Intraamniotic IL-1α causes an acute detrimental inflammatory response in the ileum, suggesting that induction of IL-1 is a critical element in the pathophysiological effects of endotoxin induced chorioamnionitis. A disturbed balance between T-effector and FoxP3+ cells may contribute to this process.
authors.affiliation: Department of Pediatrics, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Tim G A M
authors.initials: TG
authors.lastname: Wolfs
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
authors.forename: J Jane
authors.initials: JJ
authors.lastname: Pillow
authors.forename: Ilias
authors.initials: I
authors.lastname: Nitsos
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Claire A
authors.initials: CA
authors.lastname: Chougnet
authors.forename: Elke
authors.initials: E
authors.lastname: Kroon
authors.forename: Julia
authors.initials: J
authors.lastname: Spierings
authors.forename: Coen H M P
authors.initials: CH
authors.lastname: Willems
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002821:Chorioamnionitis / Q000276:immunology / Q000473:pathology*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000473:pathology*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D053582:Interleukin-1alpha / Q000008:administration & dosage / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D034561:Sheep, Domestic; D062826:Zonula Occludens-1 Protein
chemical_list: D050556:Fatty Acid-Binding Proteins; D051858:Forkhead Transcription Factors; D053582:Interleukin-1alpha; D008565:Membrane Proteins; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; D009195:Peroxidase