Airway epithelial cytokine responses in childhood wheeze are independent of atopic status

Catherine M. McDougall1， Peter J. Helms， Garry M. Walshe

1Department of Respiratory Paediatrics, Royal Hospital for Sick Children, Sciennes Road, Edinburgh EH9 1LF, UK

Background

Airway epithelial cells (AEC) are key contributors to immune function in the lungs but little is known about their role and function in children.

Objectives

Having previously established that nasal AEC mediator release correlates with that of bronchial AEC, we assessed AEC responses in children with and without a history of wheeze.

Methods

Nasal AEC cultures were established from children (0.6–14.9 years) undergoing elective surgical procedures under general anaesthetic categorised as atopic asthmatic (n = 12), virus-induced wheeze (n = 8) or children without wheeze (n = 32). Mediator release by AEC monolayers at passage 2 was determined by cytometric bead array assay or ELISA.

Results

Unstimulated AEC from children with a history of wheeze produced significantly less IL-8, IL-6, MCP-1 and G-CSF than AEC from healthy controls. There were no group differences in AEC release of VEGF, RANTES, MMP-9 or TIMP-1. After stimulation with the pro-inflammatory cytokines IL-1β and TNFα, AEC from children with current wheeze produced significantly less IL-8, IL-6 and MCP-1 than children without wheeze. Release of G-CSF, VEGF, MMP-9 and TIMP-1 did not differ between the wheeze and control group. There were no differences in mediator release between subjects with atopic asthma and those with virus-induced wheeze or between atopic and non-atopic controls. On multivariate analysis, wheeze was the only significant predictor of AEC mediator release.

Conclusion & clinical relevance

Intrinsic differences in AEC from children with a history of wheeze may reflect a defect in cytokine production in vivo or an altered state of differentiation in vitro, independent of atopic status.

respiratory medicine

June 2015Volume 109, Issue 6, Pages 689–700

DOI: http://dx.doi.org/10.1016/j.rmed.2015.04.001 |