We examined the in vivo immune response of infants to natural respiratory syncytial virus (RSV) infection through analysis of cytokine levels in nasal lavage fluid and stimulated peripheral blood mononuclear cells. Eighty-eight babies with at least one parent with atopy and asthma were prospectively studied through their first winter. Twenty-eight infants had an upper respiratory tract infection where RSV was detected, of whom nine developed signs of acute bronchiolitis. Nasal lavage specimens were assayed for interferon-gamma, interleukin (IL)-4, IL-10, and IL-12 and the RSV load determined by quantitative polymerase chain reaction. Messenger RNA (mRNA) was extracted from stimulated peripheral blood mononuclear cells and interferon-gamma, IL-4, IL-12, and IL-18 mRNA levels determined by polymerase chain reaction. Cytokine profiles were analyzed in relation to clinical outcome. The IL-4/interferon-gamma ratio for infants with acute bronchiolitis was elevated in nasal lavage fluid on both Days 1-2 (p = 0.014) and Days 5-7 (p = 0.001) of the illness compared with infants with upper respiratory tract infection alone. Those with acute bronchiolitis demonstrated a higher IL-10/IL-12 ratio (p = 0.0015) on Days 1-2. IL-18 mRNA levels were reduced (p = 0.019) and the IL-4/interferon-gamma ratio elevated (p = 0.01) in stimulated peripheral blood mononuclear cells from infants with acute bronchiolitis. There was no difference in initial RSV load. These data strongly implicate excess type 2 and/or deficient type 1 immune responses in the pathogenesis of RSV bronchiolitis.

Links between immune responses to respiratory syncytial virus (RSV), age and atopic sensitisation are poorly understood.This study investigated the induction of target organ type-1, type-2 and proinflammatory cytokine responses to RSV and/or phytohaemagglutinin (PHA) in tonsillar mononuclear cells from children, in relation to age and atopic status.In comparison with the control medium, RSV induced production of the type-1 cytokines interferon (IFN)-c and interleukin (IL)-18, the pro-inflammatory cytokines IL-6, -8 and RANTES (regulated on activation, normal T-cell expressed and secreted), but not any of the type-2 cytokines IL-4, -5, -10 and -13. Induction of IL-6, -8 and RANTES, but not IFN-c or IL-18, were shown to be dependent on virus replication. PHA induced all except IL-12, -13, and -15. Induction of IFN-c, IL-6, -8, and RANTES was significantly increased in atopic children. Induction of both IFN-c and IL-4 increased in parallel in relation to age, with no change in the IFN-c:IL-4 ratio.These data are compatible with the hypothesis that immature type-1 immunity during early childhood plays a role in both respiratory syncytial virus bronchiolitis and in its relationship with atopy. Eur Respir J 2003; 22: 317-322.

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