Monocyte IL-10 production during respiratory syncytial virus bronchiolitisis associated with recurrent wheezing in a one-year follow-up study

Respiratory syncytial virus (RSV) bronchiolitis is associated with subseque nt recurrent wheezing episodes. To determine whether cytokine responses dur ing infection can be of predictive value for the development of recurrent w heezing, we performed a followup study in 50 hospitalized children with RSV bronchiolitis. Monocyte and lymphocyte cytokine responses In vitro were st udied during the acute phase of disease, and again during the convalescent phase, 3 to 4 wk later. Monocyte cytokine responses, including interleukin- 10 (IL-10), were measured in whole blood cultures, stimulated with lipopoly saccharide and interferon-gamma (LPS + IFN-gamma). In addition, T-cell cyto kine responses, including IFN-gamma and IL-4 production, were measured in w hole-blood cultures stimulated with phytohemagglutinin (PHA) or alpha CD2 alpha CD28. Cytokine responses were analyzed in relation to the developmen t of recurrent episodes of wheezing, documented by parents in a diary durin g a 1-yr follow-up period. IL-10 responses during the acute phase of RSV br onchiolitis were comparable to those in healthy control subjects. During th e convalescent phase, IL-10 responses were significantly increased in patie nts as compared with those in healthy control subjects (p < 0.001). At foll ow-up, 27 children (58%) had recurrent episodes of wheezing. IL-10 levels, measured during the convalescent phase, were significantly higher in patien ts who developed recurrent wheezing during the year after RSV bronchiolitis than in patients without recurrent episodes of wheezing (p = 0.006). Moreo ver, IL-10 responses during the convalescent phase correlated significantly with the number of wheezing episodes (r = 0.42, n = 46, p = 0.004). intere stingly, no association was found between IFN-gamma responses, IL-4 respons es, or IFN gamma/IL-4 ratios and recurrent wheezing. We conclude that monoc yte IL-10 responses in vitro upon stimulation with nonspecific stimuli may have predictive value for the development of recurrent wheezing after RSV b ronchiolitis. Moreover, our results indicate that not only allergen-driven Th2 cytokine responses can lead to asthmatic symptoms but also virus-induce d changes in cytokine responses may result in asthmatic symptoms.