IL-1 alpha causes lung inflammation and maturation by direct effects on preterm fetal lamb lungs.
Intra-amniotic endotoxin induces IL-1, causes chorioamnionitis, lung inflammation, lung injury and lung maturation in preterm lambs. Intra-amniotic IL-1alpha also causes chorioamnionitis, lung inflammation and lung maturation. We asked if IL-1alpha effects on the preterm lung are mediated by direct signaling to the lung rather than by indirect effects from the chorioamnionitis. To study IL-1 effects independently of chorioamnionitis, the lungs and the amniotic fluid were surgically separated in fetal sheep by diverting fetal lung fluid via a tracheostomy tube to a sialastic bag. A mini-osmotic pump delivered an intratracheal infusion of recombinant sheep IL-1alpha (10 microg) or saline (control) over 24 h. Preterm lambs were delivered 1d or 7d after the start of the infusion at 124d gestational age (Term = 150d). IL-1alpha recruited inflammatory cells and increased pro-inflammatory cytokine mRNA expression in the fetal lungs. Compared with controls, IL-1alpha did not alter lung antioxidant enzyme activity or alveolar numbers. IL-1alpha had minimal effects on the mRNA or protein expression of proteins essential for vascular development. IL-1alpha induced large increases in alveolar surfactant saturated phosphatidylcholine and increased lung gas volumes. Lung inflammation and maturation result from direct exposure of the fetal lung to a single cytokine - IL-1alpha.
Sosenko
Ilene R S
IR
Department of Pediatrics, University of Miami School of Medicine, Miami, FL 33106, USA.
Kallapur
Suhas G
SG
Nitsos
Ilias
I
Moss
Timothy J M
TJ
Newnham
John P
JP
Ikegami
Machiko
M
Jobe
Alan H
AH
D000818:Animals; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000473:pathology*; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000502:physiology*; D007260:Infusion Pumps; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000502:physiology*; D053582:Interleukin-1alpha / Q000008:administration & dosage / Q000502:physiology*; D008168:Lung / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D047928:Premature Birth; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012756:Sheep
D018836:Inflammation Mediators; D007375:Interleukin-1; D053582:Interleukin-1alpha; D011994:Recombinant Proteins