Bidirectional interactions between viral respiratory illnesses and cytokine responses in the first year of life

James E. Gern, G. Daniel Brooks, Patricia Meyer, Andy Chang, Kunling Shen, Michael D. Evans, Chris Tisler, Douglas DaSilva, Kathy A. Roberg, Lance D. Mikus, Louis A. Rosenthal, Carole J. Kirk, Peter A. Shult, Abhik Bhattacharya, Zhanhai Li, Ronald Gangnon, Robert F. Lemanske

Research output: Contribution to journalArticlepeer-review

138 Scopus citations


Background: Viral infections are the major cause of acute wheezing illnesses in childhood. Variations in immunologic responses at birth may be determinants of the risk of acquiring these illnesses. Objectives: To determine the immunologic risk factors for virus-induced wheezing in high-risk infants. Methods: The study involves 285 children with a parental history of asthma and/or respiratory allergies. Mononuclear cells obtained at birth (umbilical cord blood) and at 1 year of age were incubated with phytohemagglutinin, respiratory syncytial virus, or rhinovirus, and supernatants were analyzed for IL-5, IL-10, IL-13, and IFN-γ. Nasal secretions obtained at well child visits and during respiratory illnesses were analyzed for common respiratory viruses. Results: Respiratory syncytial virus-induced wheezing was associated with reduced phytohemagglutinin-induced IL-13 responses (medians, 213 vs 304 pg/mL; P = .026) from cord blood cells, and similar trends were found for wheezing in general. Furthermore, median IL-13 responses diminished by 28% in nonwheezing children by age 1 year, versus only 3% in wheezing children (P = .013). Children with ≥2 episodes of wheezing had lower phytohemagglutinin- induced IFN-γ responses and were less likely to have rhinovirus-induced IFN-γ responses at birth (P < .05). Finally, children with measurable cord blood IFN responses to respiratory syncytial virus were less likely to wheeze in their first year (odds ratio, 0.43 [0.23, 0.79]). Conclusion: In children with a family history of allergies and/or asthma, mononuclear cell phytohemagglutinin-induced IL-13 and virus-induced IFN-γ responses at birth are indicative of the risk for wheezing in the first year of life.

Original languageEnglish (US)
Pages (from-to)72-78
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jan 2006
Externally publishedYes

Bibliographical note

Funding Information:
Supported by National Institutes of Health grants R01HL61879-01, P01HL70831-01, and 5M01 RR03186-18.


  • Atopy
  • Birth cohort
  • Bronchiolitis
  • Cytokines
  • IFN-γ
  • IL-13
  • Respiratory syncytial virus
  • Rhinoviruses
  • Viral infections
  • Wheezing


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