Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs.
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.
Kallapur
Suhas G
SG
Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology, Ohio 45229-3039, USA. suhas.kallapur@cchmc.org
Kramer
Boris W
BW
Moss
Timothy J M
TJ
Newnham
John P
JP
Jobe
Alan H
AH
Ikegami
Machiko
M
Bachurski
Cindy J
CJ
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
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