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Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Infants with evolving bronchopulmonary dysplasia demonstrate monocyte-specific expression of IL-1 in tracheal
Laurie C Eldredge1, Rane S Creasy2, Scott Presnell3
1Division of Pulmonary and Sleep Medicine, Department of Pediatrics, University of Washington, Seattle, Washington.
Insights
Investigating monocytes in premature infants revealed increased IL-1 cytokine pathway activity. These early inflammatory changes in monocytes may predict bronchopulmonary dysplasia (BPD) respiratory outcomes.
Area of Science:
- Neonatal immunology
- Respiratory medicine
- Inflammatory pathways
Background:
- Bronchopulmonary dysplasia (BPD) is a severe complication of prematurity, often exacerbated by inflammation.
- Current understanding lacks predictors for BPD respiratory outcomes and targeted therapies.
Purpose of the Study:
- To investigate inflammatory mechanisms in the development of BPD.
- To characterize monocyte molecular profiles in tracheal aspirates from high-risk infants.
Main Methods:
- Flow cytometry was used to identify myeloid cell populations in tracheal aspirates.
- RNA sequencing and quantitative PCR analyzed gene expression in monocytes.
- Differential gene expression was assessed over the first weeks of life.
Main Results:
- Monocytes were identified as CD14+CD16+ and CD14+CD16- populations.
- Expression of IL-1A, IL-1B, and IL-1 receptor antagonist mRNA increased significantly from day of life (DOL) 3 to DOL 7, 14, and 28.
- Early alterations in monocyte IL-1 cytokine pathways were observed.
Conclusions:
- Early changes in monocyte-specific IL-1 cytokine pathways are associated with evolving BPD.
- This finding may offer insights into BPD pathogenesis and potential therapeutic targets.
Abstract:
Bronchopulmonary dysplasia (BPD) remains a devastating consequence of prematurity. Repeated inflammatory insults worsen lung injury, but there are no predictors for BPD-related respiratory outcomes or targeted therapies. We sought to understand inflammatory mechanisms in evolving BPD through molecular characterization of monocytes in tracheal aspirates from infants at risk for developing BPD. We performed flow cytometry targeting myeloid cell populations on prospectively collected tracheal aspirates from intubated patients born before 29 wk of gestation and <30 days old. We identified CD14+CD16+ (double-positive) and CD14+CD16- (single-positive) monocytes and characterized their gene expression profiles by RNA sequencing and quantitative PCR. We further analyzed differential gene expression between time points to evaluate changes in monocyte function over the first weeks of life. Expression of IL-1A, IL-1B, and IL-1 receptor antagonist mRNA was increased in monocytes collected at day of life (DOL) 7, DOL 14, and DOL 28 compared with those collected at DOL 3. This study suggests that early changes in monocyte-specific IL-1 cytokine pathways may be associated with evolving BPD.
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