Variations in Human Rhinovirus (Hrv)-Induced Cytokine Release from Human Alveolar Macrophages Obtained from Individuals with Different Asthma Severity

RATIONALE: HRV infections are a major cause of exacerbations in chronic respiratory conditions, and previous studies suggest that airway macrophages are central to the innate immune response to HRV. Interestingly, striking similarities exist between features of severe asthma and the response to respiratory infections in asthma, including intensity of airflow obstruction, neutrophilic inflammation, and diminished response to corticosteroids. Therefore, we are examining the idea that macrophage phenotype can contribute to the cytokine dysregulation and airway dysfunction associated with severe asthma. METHODS: BAL fluid macrophages from 37 patients, including non-asthmatics and asthmatic individuals with a wide range of disease severity, were evaluated for pulmonary function and underwent bronchoalveolar lavage (BAL). BAL cells were treated ex vivo with a major group (HRV-16) or minor group (HRV-1a) rhinovirus for 72h and cytokine release was assessed via ELISA. The amounts of cytokines released were compared to other pulmonary parameters (including asthma severity, FEV1 % predicted, exhaled nitric oxide (eNO), IgE and methacholine PC20) for statistical significance. RESULTS: Overall, the release of cytokines from macrophages of severe asthmatics was generally reduced as compared to cytokine release seen in normal or non-severe asthmatics. The release of many of the tested cytokines (IL-1Ra, CXCL10, CCL2, CCL8, CCL-18) in response to HRV correlated significantly with both airway hyperreactivity (p = 0.003-0.02) and eNO levels (p = 0.009-0.05). CONCLUSIONS: These data suggest that severe asthmatics may have an attenuated ability to mount a robust immune response after HRV exposure, which may impair viral clearance, and thus contribute to exacerbations.