Dexamethasone Alters Tracheal Aspirate T-Cell Cytokine Production in Ventilated Preterm Infants.

Siamak M Yazdi,Jennifer K Mulligan,Colby D Richardson,John E Baatz,Ekta U Patel,Rita M Ryan,K Thomas Hardy

doi:10.3390/children8100879

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.

Highlights

Postnatal corticosteroids are used in preterm infants with evolving or established bronchopulmonary dysplasia (BPD) with the aim of reducing inflammation in the lung to improve respiratory status and facilitate weaning of respiratory support
There was a wide range of birth weights and weights at time of treatment, as well as an array of gestational ages present
We aimed to explore whether treatment with dexamethasone leads to a In change in T-cell populations in tracheal aspirates (TA) of mechanically ventilatedleads this pilot study, we aimedortocytokine exploreexpression whether treatment with dexamethasone resulting data support our hypothesis thatofdexamethasone treattopremature a changeinfants

Summary

Introduction

Postnatal corticosteroids are used in preterm infants with evolving or established bronchopulmonary dysplasia (BPD) with the aim of reducing inflammation in the lung to improve respiratory status and facilitate weaning of respiratory support Previous studies demonstrate that corticosteroid treatment leads to decreased duration of ventilation, decreased oxygen requirement, and improved pulmonary function [1,2,3,4,5]. When compared to hydrocortisone and methylprednisolone, dexamethasone therapy has been shown to have a slightly greater benefit to short-term respiratory outcomes by day 7 as assessed by reduction in respiratory severity score (RSS, defined as the mean airway pressure multiplied by the fractional inspired content of oxygen) [6]. Corticosteroids have numerous anti-inflammatory and immunomodulating effects, which may explain their benefits in ventilator-dependent preterm infants

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