Mechanisms of asthma and allergic inflammation
Bidirectional interactions between viral respiratory illnesses and cytokine responses in the first year of life

https://doi.org/10.1016/j.jaci.2005.10.002Get rights and content

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.

Section snippets

Study population and experimental design

After obtaining informed consent, 289 subjects were enrolled in the Childhood Origins of ASThma (COAST) Study14 at birth, and 285 were followed prospectively for at least 1 year. To be eligible, each of the children were required to have 1 or both parents with allergic rhinitis (1 or more positive aeroallergen skin tests) and/or asthma (by history), be delivered at ≥37 weeks gestation, and be otherwise healthy. Data collected by questionnaires included parent and child health histories with a

Study subjects and wheezing episodes

Eighty-nine of the 285 children followed through infancy (31%) had a total of 179 wheezing episodes (Fig 1). Viruses were detected in 118 (66%) nasal lavage specimens obtained during wheezing episodes, and the viruses found most often were RSV (n = 51) and rhinovirus (n = 59). Smaller numbers of wheezing episodes were attributed to parainfluenza (n = 16), influenza (n = 4), echovirus (n = 1), and adenoviruses (n = 1). There were a small number of dual infections (n = 14), most commonly with RSV

Discussion

Altered immune responses have been measured after severe respiratory infections in infancy, particularly those caused by RSV, but understanding the interactions between viral infections and immune responses has been limited by a paucity of information describing preinfection immune responses. In this study, we prospectively measured immune responses and identified specific viral respiratory infections in early infancy. Our results demonstrate that mitogen-induced and cytokine-induced responses

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    Disclosure of potential conflict of interest: R. Lemanske has consultant arrangements with AstraZeneca, Aventis, and Novartis, and is on the speakers bureau for Merck, GlaxoSmithKline, AstraZeneca, and Aventis. The rest of the authors have no conflict of interest to disclose.

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

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