Nasal cytokine responses to natural colds in asthmatic children



Marc B. Hershenson, University of Michigan Medical School, 1150 W. Medical Center Dr., Building MSRB2, Room 3570B, Ann Arbor, MI 48109-5688, USA.




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.