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Dexamethasone Alters Tracheal Aspirate T-Cell Cytokine Production in Ventilated Preterm Infants
Siamak M Yazdi1,2, Ekta U Patel1,3, Colby D Richardson4
1Department of Pediatrics-Neonatology, Medical University of South Carolina, Charleston, SC 29425, USA.
Insights
Postnatal dexamethasone treatment reduced specific T-cell cytokines in tracheal aspirates of preterm infants with bronchopulmonary dysplasia (BPD). This reduction correlated with improved respiratory status, suggesting a novel therapeutic mechanism.
Area of Science:
- Neonatal Medicine
- Immunology
- Respiratory Medicine
Background:
- Postnatal corticosteroids are used to manage bronchopulmonary dysplasia (BPD) in preterm infants.
- Corticosteroids alter cytokine profiles and T-cell presence, but their effect on tracheal aspirate (TA) T-cell phenotype and cytokine production in BPD is not well understood.
Purpose of the Study:
- To investigate the impact of postnatal dexamethasone on T-cell populations and intracellular cytokine profiles in the tracheal aspirates of preterm infants with evolving BPD.
Main Methods:
- Tracheal aspirate samples were collected from 14 preterm infants before and after a 10-day dexamethasone course.
- Flow cytometry was used to analyze T-cell populations (CD4+, CD8+) and intracellular cytokine expression (IL-6, IL-2, IFN-γ) in TA.
- Respiratory Severity Score (RSS) was assessed as a measure of respiratory status.
Main Results:
- Dexamethasone treatment led to significant decreases in RSS, CD4+IL-6+, CD8+IL-6+, CXCR3+IL-6+, and CXCR3+IL-2+ cells in TA.
- Total intracellular IFN-γ also decreased significantly following dexamethasone.
- A significant correlation was observed between reduced TA CD4+IL-6+ cells and improved RSS.
Conclusions:
- Postnatal dexamethasone effectively reduces IL-6 production by T-cells in the airways of preterm infants with BPD.
- This reduction in T-cell IL-6 is associated with improved respiratory status, indicating a potential mechanism for corticosteroid efficacy in BPD management.
Abstract:
Postnatal corticosteroids improve respiratory status and facilitate respiratory support weaning in preterm infants with bronchopulmonary dysplasia (BPD). Older literature describes characteristic cytokine profiles in tracheal aspirates (TA) of BPD patients which are altered with corticosteroids. Corticosteroids also influence peripheral blood T-cell presence. However, little is known regarding TA T-cell phenotype and cytokine production before or after exogenous corticosteroids. We hypothesized that postnatal dexamethasone alters the TA T-cell cytokine profiles of preterm infants. TA samples were collected from 14 infants born from 23 0/7 to 28 6/7 weeks who were mechanically ventilated for at least 14 days. Samples were collected up to 72 h before a ten-day dexamethasone course and again 1 to 3 calendar days after dexamethasone initiation. The primary outcome was change in T cell populations present in TA and their intracellular cytokine profile after dexamethasone treatment, ascertained via flow cytometry. Following dexamethasone treatment, there were significant decreases in respiratory severity score (RSS), percent CD4+IL-6+ cells, CD8+IL-6+ cells, CXCR3+IL-6+ cells, and CXCR3+IL-2+ cells and total intracellular IFN-γ in TA. RSS significantly correlated with TA percent CD4+IL-6+ cells. To our knowledge, this is the first study demonstrating that dexamethasone reduced T-cell IL-6 and this reduction was associated with improved RSS in pre-term infants with evolving BPD.
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