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

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Abstract
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)‐γ 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 stimulatedin vitrowith RSV, house-dust mite, birch and cat antigens. Cellular proliferation, and enzyme-linked immunoSPOT IFN‐γ 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‐γ response to RSV) were equally strong in exbronchiolitics and controls.Respiratory syncytial virus infection primes memory T‐cells that make interferon‐γ, 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.