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

BackgroundViral 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.ObjectivesTo determine the immunologic risk factors for virus-induced wheezing in high-risk infants.MethodsThe 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.ResultsRespiratory 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]).ConclusionIn 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.