Sputum neutrophil mediators in experimental rhinovirus infection in COPD

Background. Acute exacerbations of COPD (AECOPD) are associated with neutrophilic airway inflammation. Inhibition of TNF-α was recently found to be ineffective in AECOPD. We used experimental rhinovirus (RV) infection to investigate neutrophil chemokines in AECOPD. Methods. 9 COPD subjects, 9 smokers (SMK) and 8 non-smokers (NS) were successfully infected with RV. Induced sputum (IS) was collected prior to infection and on days 3, 5, 9, 12, 15, 21 and 42 post-infection. Levels of IL-8, GM-CSF, IL-1β, TNF-α, GRO-α and MMP-9 were measured in IS supernatants using the Meso Scale Discovery (MSD®) platform. Results. MMP-9, IL-8, GM-CSF, IL-1β, and TNF-α in IS increased significantly from baseline following RV infection in the COPD group but not in the SMK or NS, GRO-α was not induced. Peak levels correlated with inflammatory cell counts, neutrophil numbers and neutrophil elastase (NE) in IS in the COPD subjects. Conclusions. IL-8, GM-CSF, IL-1β, and TNF-α, but not GRO-α, are all involved in neutrophilic inflammation in AECOPD. Inhibition of single cytokines is unlikely to be successful in AECOPD. High levels of the protease MMP-9 are induced so NE inhibition may also be unsuccessful. Therapeutic strategies that target multiple chemokines or multiple proteases are likely to be required in AECOPD.