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


OBJECTIVE
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.


CONCLUSIONS
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.
Department of Child Health, University of Aberdeen, Aberdeen, UK.
Catherine M
CM
McDougall
Department of Child Health, University of Aberdeen, Aberdeen, UK.
Peter J
PJ
Helms
School of Medicine & Dentistry, University of Aberdeen, Aberdeen, UK. Electronic address: g.m.walsh@abdn.ac.uk.
Garry M
GM
Walsh
D000293:Adolescent; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D012135:Respiratory Sounds / Q000276:immunology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C111835:CCL2 protein, human; C483024:CCL5 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor
Airway epithelium; Children; Mediator release; Wheeze