title: Responses of the spleen to intraamniotic lipopolysaccharide exposure in fetal sheep.
abstract: BACKGROUND
  Intrauterine inflammation activates the fetal immune system and can result in organ injury and postnatal complications in preterm infants. As the spleen is an important site for peripheral immune activation, we asked how the fetal spleen would respond to intrauterine inflammation over time. We hypothesized that intraamniotic lipopolysaccharide (IA LPS) exposure induces acute and persistent changes in the splenic cytokine profile and T-cell composition that may contribute to the sustained fetal inflammatory response after chorioamnionitis.
  
  
  METHODS
  Fetal sheep were exposed to IA LPS 5, 12, and 24 h and 2, 4, 8, or 15 d before delivery at 125 d of gestational age (term = 150 d). Splenic cytokine mRNA levels and cleaved caspase-3, CD3, and Foxp3 expression were evaluated.
  
  
  RESULTS
  IA LPS increased interleukin (IL)1, IL4, IL5, and IL10 mRNA by twofold 24 h after injection. Interferon gamma increased by fivefold, whereas IL23 decreased 15 d post-LPS exposure. Cleaved caspase-3-positive cells increased 2 and 8 d after LPS exposure. CD3 immunoreactivity increased within 5 h with increased Foxp3-positive cells at 12 h.
  
  
  CONCLUSIONS
  Intrauterine inflammation induced a rapid and sustained splenic immune response with persistent changes in the cytokine profile. This altered immune status may drive sustained inflammation and injury in other fetal organs.
authors.affiliation: Department of Pediatrics, School of Mental Health and Neuroscience, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Elke
authors.initials: E
authors.lastname: Kuypers
authors.affiliation: Department of Pediatrics, School of Mental Health and Neuroscience, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Monique G M
authors.initials: MG
authors.lastname: Willems
authors.affiliation: Department of Pediatrics, School of Mental Health and Neuroscience, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Reint K
authors.initials: RK
authors.lastname: Jellema
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kemp
authors.affiliation: School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia.
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.affiliation: Department of Pediatrics, School of Mental Health and Neuroscience, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Tammo
authors.initials: T
authors.lastname: Delhaas
authors.affiliation: 1] School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia [2] Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
authors.affiliation: 1] School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia [2] Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.affiliation: Department of Pediatrics, School of Mental Health and Neuroscience, 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.affiliation: 1] Department of Pediatrics, School of Mental Health and Neuroscience, School of Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands [2] School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia.
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
mesh_terms: D000653:Amniotic Fluid / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002821:Chorioamnionitis / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D005865:Gestational Age; D007107:Immune System; D007249:Inflammation; D053759:Interleukin-23 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry*; D023421:Models, Animal; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D013154:Spleen / Q000276:immunology* / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D053759:Interleukin-23; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D053148:Caspase 3