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Enhanced IL-4 responses in children with a history of respiratory syncytial virus bronchiolitis in infancy

¹ Dept of Respiratory Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Norfolk Place, London, UK. ² Dept of Paediatrics, Sahlgrenska University Hospital, Gothenburg, Sweden. ³ Emergency Dept, Reykjavik Hospital, Iceland. ⁴ Medical Research Council Biostatistics Unit, Cambridge, UK. ⁵ Dept of Paediatrics, Borås Central Hospital, Sweden

CORRESPONDENCE: P. Pala, Respiratory Medicine, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Norfolk Place, London, W2 1PG, UK. Fax: 44 2072628913. E-mail: p.pala@ic.ac.uk

Keywords: asthma, human, interleukin-4, lymphocytes, respiratory syncytial virus

Received: June 1, 2001
Accepted March 20, 2002

P.J.M. Openshaw and P. Pala thank the Wellcome Trust for generous support (programme grant 054797/Z/98/Z). N. Sigurs was supported by grants from the Regional Healthcare Authority of West Sweden, the Swedish Foundation for Healthcare Sciences and Allergy Research and BeDe's fund.

Infants who recover from respiratory syncytial virus (RSV)-induced bronchiolitis are at high risk of developing asthma and recurrent wheezing. It is not known whether severe RSV infection itself causes persistent effects or is a marker of a "wheezy" predisposition. To determine the long-term immunological correlates of infantile bronchiolitis, interleukin (IL)-4 and interferon (IFN)- responses to a panel of antigens were studied in a well-characterised cohort of 7–8-yr-old children with a history of severe RSV bronchiolitis in infancy.

Peripheral blood lymphocytes from 37 children who were hospitalised with RSV bronchiolitis in infancy and from 69 age-, sex- and location-matched controls were stimulated in vitro with RSV, house-dust mite, birch and cat antigens. Cellular proliferation, and enzyme-linked immunoSPOT IFN- and IL-4 production were measured.

IL-4 producing T-cells responding to RSV and cat antigens were significantly more frequent in exbronchiolitics. Other responses (including the IFN- response to RSV) were equally strong in exbronchiolitics and controls.

Respiratory syncytial virus infection primes memory T-cells that make interferon-, but virus and aeroallergen-specific and interleukin-4 producing T-cells are also frequently primed in bronchiolitics. Respiratory syncytial virus bronchiolitis in infancy may increase the risk of allergic sensitisation by providing a local interleukin-4-rich environment, in which airborne allergens are first encountered.

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