title: Nasal cytokine responses to natural colds in asthmatic children.
abstract: BACKGROUND
  The mechanisms by which viruses induce asthma exacerbations are not well understood.
  
  
  OBJECTIVE
  We characterized fluctuations in nasal aspirate cytokines during naturally occurring respiratory viral infections in children with asthma.
  
  
  METHODS
  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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Lewis
authors.forename: T A
authors.initials: TA
authors.lastname: Henderson
authors.forename: A R
authors.initials: AR
authors.lastname: Carpenter
authors.forename: I A
authors.initials: IA
authors.lastname: Ramirez
authors.forename: C L
authors.initials: CL
authors.lastname: McHenry
authors.forename: A M
authors.initials: AM
authors.lastname: Goldsmith
authors.forename: X
authors.initials: X
authors.lastname: Ren
authors.forename: G B
authors.initials: GB
authors.lastname: Mentz
authors.forename: B
authors.initials: B
authors.lastname: Mukherjee
authors.forename: T G
authors.initials: TG
authors.lastname: Robins
authors.forename: T A
authors.initials: TA
authors.lastname: Joiner
authors.forename: L S
authors.initials: LS
authors.lastname: Mohammad
authors.forename: E R
authors.initials: ER
authors.lastname: Nguyen
authors.forename: M A
authors.initials: MA
authors.lastname: Burns
authors.forename: D T
authors.initials: DT
authors.lastname: Burke
authors.forename: M B
authors.initials: MB
authors.lastname: Hershenson
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000276:immunology / Q000821:virology; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000276:immunology / Q000378:metabolism; D008297:Male; D009296:Nasal Cavity / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D014777:Virus Diseases / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D014780:Viruses / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D018925:Chemokines; D016207:Cytokines; D007372:Interferons