Background: Airway inflammation in chronic obstructive pulmonary disease ( COPD) is predominately neutrophilic, but some subjects demonstrate eosinophilic airway inflammation. Whether these inflammatory phenotypes have differential cytokine and chemokine expression is unknown. Objectives: To assess the sputum concentrations of cytokines and chemokines and their response to oral corticosteroid therapy in COPD subjects with or without a sputum eosinophilia. Methods: Cytokine and chemokine concentrations were measured using the meso-scale device platform. To assess validity, recovery of exogenous spikes was examined. The concentrations of the validated mediators were measured in COPD sputum from subjects with or without a sputum eosinophilia. In a subgroup with a sputum eosinophilia, the response to oral prednisolone 10 mg for 1 month was examined. Results: The recovery in sputum of exogenous spiked mediators was > 80% in 11/26 cytokines and chemokines. In supernatants from eosinophilic (n = 39) versus non-eosinophilic (n = 59) sputa, the geometric mean ( 95% CI) concentration was increased for IL-5 [9.0 (4.5-18) pg/ml vs. 3.6 (2.7-6.3) pg/ml, p = 0.03]. IL-5 alone was correlated with sputum eosinophil counts (r = 0.33, p = 0.001), and was attenuated following treatment with prednisolone [n = 9; mean difference 2.3 pg/ml (0.2-4.3), p = 0.032]. Conclusion: We have validated the use of the meso-scale device platform for cytokine and chemokine measurements in the sputum supernatants in COPD. Sputum IL-5 was associated with a sputum eosinophilia and was attenuated following oral corticosteroid therapy. Whether this cytokine is important in the pathogenesis of COPD in a subgroup of patients warrants further investigation. Copyright (C) 2009 S. Karger AG, Basel