Nasal cytokine responses to natural colds in asthmatic children
Article first published online: 26 NOV 2012
© 2012 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 42, Issue 12, pages 1734–1744, December 2012
How to Cite
Cite this as: Clinical & Experimental Allergy 2012 (42) 1734–1744., , , , , , , , , , , , , , and ,
- Issue published online: 26 NOV 2012
- Article first published online: 26 NOV 2012
- Accepted manuscript online: 27 AUG 2012 06:23AM EST
- Manuscript Accepted: 10 JUL 2012
- Manuscript Revised: 7 JUN 2012
- Manuscript Received: 3 FEB 2012
- National Institutes of Health grants. Grant Numbers: R01ES016769, UL1RR024986, R01HL081420
- respiratory infection;
The mechanisms by which viruses induce asthma exacerbations are not well understood.
We characterized fluctuations in nasal aspirate cytokines during naturally occurring respiratory viral infections in children with asthma.
Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured using multiplex immune assay. mRNA expression for selected markers of viral infection was measured using RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score.
The 16 patients completed a total of 37 weeks of assessment (15 ‘well’ weeks; 22 self-assessed ‘sick’ weeks). Viral infections were detected in 3 of the ‘well’ weeks and 17 of the ‘sick’ weeks (10 rhinovirus, three coronavirus, two influenza A, two influenza B, two respiratory syncytial virus, one parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1β, CCL7/MCP-3, and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5, and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I, and IRF7 mRNA.
Conclusions and clinical relevance
We conclude that in children with asthma, naturally occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs, and IFN-responsive genes.