The Journal of Allergy and Clinical Immunology
Volume 117, Issue 1 , Pages 72-78, January 2006

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

  • James E. Gern, MD

      Affiliations

    • From the Departments of Pediatrics
    • Corresponding Author InformationReprint requests: James E. Gern, MD, K4/918 CSC, University of Wisconsin Hospital, 600 Highland Avenue, Madison, WI 53792-9988.
  • ,
  • G. Daniel Brooks, MD

      Affiliations

    • Medicine
  • ,
  • Patricia Meyer, MD

      Affiliations

    • Universidad de Buenos Aires
  • ,
  • Andy Chang, BS

      Affiliations

    • From the Departments of Pediatrics
  • ,
  • Kunling Shen, MD

      Affiliations

    • Bejing Children's Hospital
  • ,
  • Michael D. Evans, MS

      Affiliations

    • Biostatistics and Medical Informatics, University of Wisconsin-Madison
  • ,
  • Chris Tisler, MS

      Affiliations

    • From the Departments of Pediatrics
  • ,
  • Douglas DaSilva, BS

      Affiliations

    • From the Departments of Pediatrics
  • ,
  • Kathy A. Roberg, MSN

      Affiliations

    • From the Departments of Pediatrics
  • ,
  • Lance D. Mikus, MBA

      Affiliations

    • From the Departments of Pediatrics
  • ,
  • Louis A. Rosenthal, PhD

      Affiliations

    • From the Departments of Pediatrics
  • ,
  • Carole J. Kirk, BS

      Affiliations

    • Wisconsin State Laboratory of Hygiene
  • ,
  • Peter A. Shult, PhD

      Affiliations

    • Wisconsin State Laboratory of Hygiene
  • ,
  • Abhik Bhattacharya, MS

      Affiliations

    • Biostatistics and Medical Informatics, University of Wisconsin-Madison
  • ,
  • Zhanhai Li, PhD

      Affiliations

    • Biostatistics and Medical Informatics, University of Wisconsin-Madison
  • ,
  • Ronald Gangnon, PhD

      Affiliations

    • Biostatistics and Medical Informatics, University of Wisconsin-Madison
  • ,
  • Robert F. Lemanske Jr., MD

      Affiliations

    • From the Departments of Pediatrics
    • Medicine

Received 24 April 2005; received in revised form 27 September 2005; accepted 3 October 2005. published online 29 November 2005.

Madison, Wis, Bejing, China, and Buenos Aires, Argentina

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.

Key words: Respiratory syncytial virus, rhinoviruses, wheezing, IL-13, cytokines, viral infections, bronchiolitis, IFN-γ, atopy, birth cohort

Abbreviations used: COAST, Childhood Origins of ASThma, RSV, Respiratory syncytial virus

 

 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.

PII: S0091-6749(05)02137-8

doi:10.1016/j.jaci.2005.10.002

The Journal of Allergy and Clinical Immunology
Volume 117, Issue 1 , Pages 72-78, January 2006