title: Betamethasone effects on chorioamnionitis induced by intra-amniotic endotoxin in sheep.
abstract: OBJECTIVE
  Intra-amniotic administration of endotoxin in sheep is a model of subclinical chorioamnionitis. Intrauterine inflammation alters lung development to improve postnatal lung function and may predispose the infant to lung and brain injury. We describe the effects of intra-amniotic endotoxin on cytokines and white cell responses in the membranes and amniotic fluid and investigate the hypothesis that betamethasone treatment suppresses these responses.
  
  
  METHODS
  Pregnant ewes were allocated at random to receive either intra-amniotic saline solution (control animals), maternal intramuscular betamethasone, intra-amniotic endotoxin by ultrasound guidance (10 mg Escherichia coli 055:B5), or a combination of the betamethasone and endotoxin treatments. Lambs were delivered abdominally at 110 to 125 days of gestation at time points that ranged from 2 hours to 15 days after treatment.
  
  
  RESULTS
  When compared with saline solution-injected control animals, the intra-amniotic injection of endotoxin increased white cell counts in amniotic fluid. Levels of interleukin-8, but not interleukin-6, were significantly increased in amniotic fluid from 5 hours to 15 days after intra-amniotic endotoxin injection, and interleukin-8 levels were not decreased by concurrent treatment with betamethasone. After endotoxin treatment, interleukin-1beta and interleukin-8 messenger RNA were expressed in chorion, and interleukin-6 messenger RNA expression was localized to chorionic blood vessel epithelium. The half-life of endotoxin in the amniotic fluid was 1.7 days, and levels remained measurable 15 days after injection.
  
  
  CONCLUSIONS
  These findings confirm that the fetus can survive within amniotic fluid that contains endotoxin, white cells, and cytokines for periods of weeks or more. Betamethasone treatment can suppress the initial inflammation in the amnion-chorion, but interleukin-8 levels and inflammatory cells in amniotic fluid were not suppressed 5 and 15 days after betamethasone treatment, presumably because of the slow clearance of bioactive endotoxin from the amniotic fluid.
authors.affiliation: School of Women's and Infants' Health, University of Western Australia, King Edward Memorial Hospital, Bagot Road, Subiaco, Perth, WA 6008, Australia. jnewnham@obsgyn.uwa.edu.au
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: Timothy J M
authors.initials: TJ
authors.lastname: Moss
authors.forename: Ilias
authors.initials: I
authors.lastname: Nitsos
authors.forename: Machiko
authors.initials: M
authors.lastname: Ikegami
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
mesh_terms: D000650:Amnion; D000653:Amniotic Fluid / Q000737:chemistry / Q000166:cytology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001623:Betamethasone / Q000494:pharmacology*; D001808:Blood Vessels / Q000378:metabolism; D002821:Chorioamnionitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D002823:Chorion / Q000098:blood supply / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage / Q000737:chemistry; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006207:Half-Life; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D011247:Pregnancy; D012756:Sheep
chemical_list: D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D001623:Betamethasone