Effects of antenatal endotoxin and glucocorticoids on the lungs of preterm lambs.
OBJECTIVE
We hypothesized that the proinflammatory response to intra-amniotic endotoxin would induce lung maturation in preterm lambs.


METHODS
Ewes were randomly assigned to receive 20 mg Escherichia coli endotoxin by intra-amniotic injection, maternal betamethasone (0.5 mg/kg), or sodium chloride solution. Preterm lambs were delivered at 125 days' gestation and underwent ventilation to assess lung function. Lung gas volume, surfactant concentrations, and inflammation were subsequently evaluated, with data analyzed by analysis of variance.


RESULTS
Fetal endotoxin exposure 6 days before delivery increased compliance by 59%, increased lung gas volume 2.3-fold, increased concentrations of surfactant lipids, increased surfactant A and B protein levels, and increased messenger ribonucleic acid expressions for surfactant proteins (all P <.01, vs control group). Betamethasone exposure resulted in less consistent effects. White blood cell counts were increased in fetal membranes and lungs after endotoxin exposure, but there was no severe inflammation.


CONCLUSIONS
A single fetal exposure to endotoxin resulted in large improvements in postnatal lung function and increases in surfactant concentrations after preterm delivery. These effects were qualitatively larger than those achieved with betamethasone.
Jobe
A H
AH
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Newnham
J P
JP
Willet
K E
KE
Sly
P
P
Ervin
M G
MG
Bachurski
C
C
Possmayer
F
F
Hallman
M
M
Ikegami
M
M
D000818:Animals; D000831:Animals, Newborn; D001623:Betamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid; D002585:Cesarean Section; D017931:DNA Primers / Q000737:chemistry; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000473:pathology; D008297:Male; D009693:Nucleic Acid Hybridization; D011247:Pregnancy; D011510:Proteolipids / Q000032:analysis; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000032:analysis; D012333:RNA, Messenger / Q000737:chemistry / Q000302:isolation & purification; D011897:Random Allocation; D012121:Respiration, Artificial; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep
D017931:DNA Primers; D004731:Endotoxins; D005938:Glucocorticoids; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D001623:Betamethasone