The aim of this study was to determine whether interleukin (IL)-8 is released within the upper respiratory tract of infants during respiratory syncytial virus (RSV) bronchiolitis and whether the large number of polymorphonuclear neutrophils (PMNs) present in the respiratory tract of these infants are contributing to the inflammation through release of inflammatory mediators.Twenty-seven infants with acute bronchiolitis were recruited during one winter epidemic and 20 infant control subjects were recruited from a cohort participating in a community-based vaccine study. Samples of airways fluid were obtained using nasal lavage. The lavage fluid was spun to remove the cells, and the supernatant was stored at -708C. The supernatants were subsequently assayed for the presence of IL-8, total human neutrophil elastase (HNE) and neutrophil elastase activity.In the children with bronchiolitis compared with control infants, elevated levels of IL-8 (median (range) 1.53 (0±153) versus 0 (0±5.6) ng . mL -1 ) HNE (136 (32±694) versus 14 (0±516) ng . mL -1 ) and elastase activity (4 (1±220) versus 1 (0±339) mU . mL -1 ) were found.These results indicate that interleukin-8 is released in the upper respiratory tract in response to respiratory syncytial virus infection and suggest that polymorphonuclear neutrophil products are playing an important role in the inflammatory response to respiratory syncytial virus infection in infants with acute bronchiolitis. This contrasts with the predominantly eosinophilic response evident in atopic upper and lower respiratory tract disease. Eur Respir J 1999; 14: 139±143. Respiratory syncytial virus (RSV) bronchiolitis is the commonest form of lower respiratory tract disease in infancy [1±4]. Despite intensive efforts over the past 30 yrs, the nature of the inflammatory process within the respiratory tract of infants with RSV bronchiolitis has not been clearly characterized. Many have speculated that there is a distinct immunopathological process present in the airways of infants with RSV bronchiolitis. However, the same clinical picture can be induced by a number of respiratory viruses and there is no evidence from the human host that a specific immunopathology does lead to the development of acute bronchiolitis in some infants infected with the virus. Previous work from the authors' group suggests that an intense neutrophil influx characterizes the inflammatory process in the airways of these patients and that the inflammatory response is similar in nature to that observed in viral respiratory tract infections differing only in its intensity and distribution.The initial suggestion that there may be a specific immunopathology was made >25 yrs ago and was based on the observations that: the majority of infants are infected with the virus during the first winter after their birth, but only 0.5±2% of such infants develop bronchiolitis severe enough to require hospitalization; the most severely affected individuals with RSV bronchiolitis are generally <6 months of age; and the administra...

BackgroundNeonatal Natural Killer (NK) cells show functional impairment and expansion of a CD56 negative population of uncertain significance.MethodsNK cells were isolated from cord blood and from adult donors. NK subpopulations were identified as positive or negative for the expression of CD56 and characterized for expression of granzyme B and surface markers by multi-parameter flow cytometry. Cell function was assessed by viral suppression and cytokine production using autologous lymphocytes infected with HIV. Activating (NKp30, NKp46) and inhibitory (Siglec-7) markers in healthy infants and adults were compared with viremic HIV-infected adults.ResultsCord blood contained increased frequencies of CD56 negative (CD56neg) NK cells with reduced expression of granzyme B and reduced production of IFNγ and the CC-class chemokines RANTES, MIP1α and MIP1β upon stimulation. Both CD56pos and CD56neg NK subpopulations showed impaired viral suppression in cord blood, with impairment most marked in the CD56neg subset. CD56neg NK cells from cord blood and HIV-infected adults shared decreased inhibitory and activating receptor expression when compared with CD56pos cells.ConclusionsCD56neg NK cells are increased in number in normal infants and these effectors show reduced anti-viral activity. Like the expanded CD56neg population described in HIV-infected adults, these NK cells demonstrate functional impairments which may reflect inadequate development or activation.

Reference ranges for the total and differential leucocyte counts were determined from venous blood collected at 2, 5 and 13 months of age from a cohort of 112 healthy children of north European ancestry. At 2, 5 and 13 months, the ranges for neutrophils were found to be 0.7-4.7, 1.1-5.6 and 1.0-7.6 x 109/l, and for lymphocytes 3.3-10.5, 3.4-11.3 and 3.5-10.4 x 109/l, respectively. The upper limits for monocytes at each age were 1.2, 1.2 and 0.91 x 109/l, and for eosinophils 0.84, 1.0 and 0.88 x 109/l, respectively. Mean counts for all cell types, except monocytes, increased between 2 and 5 months of age. There was little change in mean counts between 5 and 13 months. Statistically significant correlations existed between the numbers of each cell type at 2 months of age, and were still present at 13 months between monocytes and each of the granulocyte series and between basophils and all other cell types. By comparison with older data these findings indicate a lower reference limit for neutrophils at 2 months of age, and a narrower range for this cell type at both 2 and 5 months of age. Reference ranges for lymphocytes and eosinophils are wider than indicated by some previous studies.