title: Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in preterm lamb lungs.
abstract: The proinflammatory stimulus of chorioamnionitis is commonly associated with preterm delivery. Women at risk of preterm delivery receive antenatal glucocorticoids to functionally mature the fetal lung. However, the effects of the combined exposures of chorioamnionitis and antenatal glucocorticoids on the fetus are poorly understood. Time-mated ewes with singleton fetuses received an intra-amniotic injection of lipopolysaccharide (LPS) either preceding or following maternal intramuscular betamethasone 7 or 14 days before delivery, and the fetuses were delivered at 120 days gestational age (GA) (term = 150 days GA). Gestation matched controls received intra-amniotic and maternal intramuscular saline. Compared with saline controls, intra-amniotic LPS increased inflammatory cells in the bronchoalveolar lavage and myeloperoxidase, Toll-like receptor 2 and 4 mRNA, PU.1, CD3, and Foxp3-positive cells in the fetal lung. LPS-induced lung maturation measured as increased airway surfactant and improved lung gas volumes. Intra-amniotic LPS-induced inflammation persisted until 14 days after exposure. Betamethasone treatment alone induced modest lung maturation but, when administered before intra-amniotic LPS, suppressed lung inflammation. Interestingly, betamethasone treatment after LPS did not counteract inflammation but enhanced lung maturation. We conclude that the order of exposures of intra-amniotic LPS or maternal betamethasone had large effects on fetal lung inflammation and maturation.
authors.affiliation: Department of Pediatrics, School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands.
authors.forename: Elke
authors.initials: E
authors.lastname: Kuypers
authors.forename: Jennifer J P
authors.initials: JJ
authors.lastname: Collins
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: Gaston
authors.initials: G
authors.lastname: Ofman
authors.forename: Ilias
authors.initials: I
authors.lastname: Nitsos
authors.forename: J Jane
authors.initials: JJ
authors.lastname: Pillow
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kemp
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Antonio W D
authors.initials: AW
authors.lastname: Gavilanes
authors.forename: Relana
authors.initials: R
authors.lastname: Nowacki
authors.forename: Machiko
authors.initials: M
authors.lastname: Ikegami
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
mesh_terms: D000650:Amnion; D000818:Animals; D001623:Betamethasone / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002821:Chorioamnionitis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005325:Fetal Organ Maturity / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression; D005938:Glucocorticoids / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology / Q000276:immunology; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology / Q000517:prevention & control; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D012756:Sheep; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D010713:Phosphatidylcholines; D037721:Pulmonary Surfactant-Associated Protein C; D037663:Pulmonary Surfactant-Associated Protein D; D051193:Toll-Like Receptors; D001623:Betamethasone; D017258:Medroxyprogesterone Acetate; D009195:Peroxidase