TY - JOUR
T1 - Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in preterm lamb lungs
AU - Kuypers, Elke
AU - Collins, Jennifer J. P.
AU - Kramer, Boris W.
AU - Ofman, Gaston
AU - Nitsos, Ilias
AU - Pillow, J. Jane
AU - Polglase, Graeme R.
AU - Kemp, Matthew W.
AU - Newnham, John P.
AU - Gavilanes, Antonio W. D.
AU - Nowacki, Relana
AU - Ikegami, Machiko
AU - Jobe, Alan H.
AU - Kallapur, Suhas G.
PY - 2012/2
Y1 - 2012/2
N2 - Kuypers E, Collins JJ, Kramer BW, Ofman G, Nitsos I, Pillow JJ, Polglase GR, Kemp MW, Newnham JP, Gavilanes AW, Nowacki R, Ikegami M, Jobe AH, Kallapur SG. Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in preterm lamb lungs. Am J Physiol Lung Cell Mol Physiol 302: L380-L389, 2012. First published December 9, 2011; doi:10.1152/ajplung.00338.2011.-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.
AB - Kuypers E, Collins JJ, Kramer BW, Ofman G, Nitsos I, Pillow JJ, Polglase GR, Kemp MW, Newnham JP, Gavilanes AW, Nowacki R, Ikegami M, Jobe AH, Kallapur SG. Intra-amniotic LPS and antenatal betamethasone: inflammation and maturation in preterm lamb lungs. Am J Physiol Lung Cell Mol Physiol 302: L380-L389, 2012. First published December 9, 2011; doi:10.1152/ajplung.00338.2011.-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.
KW - chorioamnionitis
KW - lung inflammation
KW - surfactant
KW - bronchopulmonary dysplasia
KW - respiratory distress syndrome
U2 - 10.1152/ajplung.00338.2011
DO - 10.1152/ajplung.00338.2011
M3 - Article
C2 - 22160306
SN - 1040-0605
VL - 302
SP - L380-L389
JO - American Journal of Physiology-Lung Cellular and Molecular Physiology
JF - American Journal of Physiology-Lung Cellular and Molecular Physiology
IS - 4
ER -