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

J Allergy Clin Immunol. 2006 Jan;117(1):72-8. doi: 10.1016/j.jaci.2005.10.002. Epub 2005 Nov 28.


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-gamma. 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 non-wheezing children by age 1 year, versus only 3% in wheezing children (P = .013). Children with > or =2 episodes of wheezing had lower phytohemagglutinin-induced IFN-gamma responses and were less likely to have rhinovirus-induced IFN-gamma 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-gamma responses at birth are indicative of the risk for wheezing in the first year of life.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Common Cold / immunology
  • Cytokines / biosynthesis*
  • Humans
  • Infant
  • Infant, Newborn
  • Interferon-gamma / biosynthesis
  • Interleukin-13 / biosynthesis
  • Phytohemagglutinins / pharmacology
  • Respiratory Sounds / etiology*
  • Respiratory Syncytial Virus Infections / immunology
  • Risk Factors
  • Virus Diseases / immunology*


  • Cytokines
  • Interleukin-13
  • Phytohemagglutinins
  • Interferon-gamma