Abstract
Spontaneous preterm birth due to intrauterine infection is associated with increased concentrations of cytokines in amniotic fluid and in the airways at birth. Intra-amniotic IL-1 induces fetal lung maturity, consistent with the decrease in the incidence of respiratory distress syndrome (RDS) in intrauterine inflammation. On the other hand, antenatal corticosteroid decreases the incidence of RDS in infants born prematurely. The aim of the present study was to investigate the interaction between IL-1 and glucocorticoid in the expression of the surfactant proteins SP-A, -B, and -C. Lung explants from rabbit fetuses at 22 (immature), 27 (transitional), and 30 (mature) d of gestation (term, 30–31 d) and on d 1 after term birth were cultured with dexamethasone (Dx), IL-1α, or vehicle in the presence or absence of actinomycin D. According to the present results, IL-1α and Dx additively increased the expression of SP-A and SP-B on d 22. Later in gestation, SP-B and SP-C were suppressed by IL-1, whereas glucocorticoid tended to increase the expression of SP-B and SP-C and prevented the IL-1-induced suppression of SP. IL-1α and steroid interactively increased the stability of SP mRNA compared with the single agonist, possibly explaining the additive effects on the SP mRNA levels. The present results reveal beneficial additive effects of glucocorticoid and cytokine on lung surfactant. They may explain some of the acute beneficial effects of glucocorticoid therapy in chorioamnionitis before premature birth and in inflammatory lung disease after birth.
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Abbreviations
- Dx:
-
dexamethasone
- RDS:
-
respiratory distress syndrome
- SP:
-
surfactant protein
- LPS:
-
lipopolysaccharide
- BPD:
-
bronchopulmonary dysplasia
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Acknowledgements
The authors thank Dr. Tiina Kangas for her help in the project as well as Maarit Hännikäinen, Elsi Jokelainen, and Mirkka Parviainen for their excellent technical assistance.
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Supported by the Academy of Finland, Biocenter Oulu (M.H.) and the Foundation for Pediatric Research in Finland (O.V.).
Preliminary results were presented as an abstract at the 1999 annual meeting of the European Society of Pediatric Research in Copenhagen (Pediatr Res 1999;45(6):31).
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Väyrynen, O., Glumoff, V. & Hallman, M. Inflammatory and Anti-inflammatory Responsiveness of Surfactant Proteins in Fetal and Neonatal Rabbit Lung. Pediatr Res 55, 55–60 (2004). https://doi.org/10.1203/01.PDR.0000100462.41671.C6
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DOI: https://doi.org/10.1203/01.PDR.0000100462.41671.C6
