Intraamniotic interleukin-1 accelerates surfactant protein synthesis in fetal rabbits and improves lung stability after premature birth.
Intraamniotic infection is associated with increased IL-1 activity in amniotic fluid, increased incidence of preterm labor, and with decreased incidence of respiratory distress syndrome in infants born prematurely. We hypothesized that an elevated IL-1 in amniotic fluid promotes fetal lung maturation. On day 23 or 25 of gestation (term 31 d), either IL-1alpha (150 or 1,500 ng per fetus) or its antagonist IL-1 receptor antagonist (IL-1ra, 20 microg) was injected to the amniotic fluid sacs in one uterine horn, whereas the contralateral amniotic sacs were injected with vehicle. Within 40 h, IL-1alpha caused a dose-dependent increase in surfactant protein-A (SP-A) and SP-B mRNAs (maximally, fivefold), without affecting lung growth or increasing inflammatory cells in the lung. Both genders, and upper and lower lung lobes were similarly affected. IL-1ra did not modify SP-A, -B, or -C mRNA. IL-1 increased the intensity of staining of alveolar type II cells for SP-B, and the concentrations of SP-B, -A, and disaturated phosphatidylcholine in bronchoalveolar lavage. The dynamic lung compliance and the postventilatory expansion of lungs were increased two- to fourfold after IL-1alpha treatment. In fetal lung explants, IL-1alpha increased the expression of SP-A mRNA. IL-1 in amniotic fluid in preterm labor may promote lung maturation and thus be part of a host-defense mechanism that prepares the fetus for extrauterine life.
Bry
K
K
Department of Pediatrics, University of California, Irvine, Irvine, California 92697, USA.
Lappalainen
U
U
Hallman
M
M
D000653:Amniotic Fluid; D000818:Animals; D001835:Body Weight; D004247:DNA / Q000378:metabolism; D005260:Female; D005325:Fetal Organ Maturity; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000196:embryology*; D007752:Obstetric Labor, Premature; D009929:Organ Size; D010743:Phospholipids / Q000378:metabolism; D011247:Pregnancy; D011510:Proteolipids / Q000096:biosynthesis* / Q000235:genetics; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits
D007375:Interleukin-1; D010743:Phospholipids; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D004247:DNA