title: Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs.
abstract: Antenatal betamethasone (Beta) is widely used in women with asymptomatic chorioamnionitis at risk for preterm delivery, but its effects on fetal inflammation are unstudied. Groups of ewes at 109 +/- 1 days of gestation received the following treatments: intra-amniotic (IA) saline (control), 0.5 mg/kg intramuscular Beta, 10 mg IA endotoxin (Endo), and Beta + 2 h later Endo (Beta + Endo). Beta suppressed Endo-induced lung inflammation at 1 day. However, compared with Endo 5 days after treatment, Beta + Endo lambs had increased alveolar neutrophils, proinflammatory cytokine mRNA expression, and serum amyloid A3 (SAA3) mRNA expression. IL-1beta mRNA expression was localized to the inflammatory cells, whereas SAA3 mRNA expression was induced in the bronchial epithelium and the inflammatory cells. Compared with Endo, Beta + Endo lambs had increased lung inflammation but equivalent lung volumes 15 days after treatment. The late increase in inflammation in the Beta + Endo animals suggests that glucocorticoids impair the ability of the preterm lung to downregulate Endo-induced inflammation after fetal clearance of the glucocorticoids. These results have implications for lung inflammation and bronchopulmonary dysplasia in preterm infants exposed to chorioamnionitis and maternal glucocorticoids.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, Ohio 45229-3039, USA. suhas.kallapur@cchmc.org
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: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.forename: Machiko
authors.initials: M
authors.lastname: Ikegami
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Bachurski
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002821:Chorioamnionitis / Q000188:drug therapy; D004357:Drug Synergism; D004731:Endotoxins; D005260:Female; D015870:Gene Expression / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008168:Lung / Q000196:embryology* / Q000276:immunology*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000166:cytology; D011014:Pneumonia / Q000139:chemically induced* / Q000503:physiopathology; D011247:Pregnancy; D000685:Serum Amyloid A Protein / Q000235:genetics; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D004731:Endotoxins; D005938:Glucocorticoids; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D001623:Betamethasone; D006854:Hydrocortisone