Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection

To test the hypothesis that rhinovirus (RV)-induced immune responses influe nce the outcome of RV infections, we inoculated 22 subjects with allergic r hinitis or asthma with RV16. Nasal secretions and induced sputum were repea tedly sampled over the next 14 d. RV16 infection increased nasal granulocyt e colony-stimulating factor (C-CSF) and interleukin (IL)-8, which was accom panied by neutrophilia in blood and nasal secretions. Nasal G-CSF correlate d closely with increased blood neutrophils (r(s) = 0.69, p < 0.005), wherea s nasal neutrophils correlated with both G-CSF (r(s) = 0.87, p < 0.001) and IL-8 (r(s) = 0.75, p < 0.001). Although similar relationships were present in sputum, changes in sputum neutrophils and C-CSF with RV16 infection wer e relatively modest. In addition, virus-induced changes in the sputum inter feron-<gamma>-to-IL-5 messenger RNA ratio were inversely related to both pe ak cold symptoms (r(s) = -0.60, p < 0.005) and the time to viral clearance (undetectable picornavirus RNA). These results indicate that airway IL-8 an d C-CSF are closely associated with virus-induced neutrophilic inflammation during an experimental RV infection in atopic volunteers. In addition, the balance of airway T-helper cell type 1 (Th1)- and Th2-like cytokines induc ed by RV infection may help determine the clinical outcome of common cold i nfections, raising the possibility that the individual subject's immune res ponse, rather than atopic status per se, is important in this regard.