Th2 cytokine expression by bronchoalveolar lavage T-lymphocytes in asthma and eosinophilic bronchitis without asthma

Abstract

6 Th2 Cytokine Expression by Bronchoalveolar Lavage T-Lymphocytes in Asthma and Eosinophilic Bronchitis Without Asthma Christopher Edward Brightling, Fiona A Symon, Surinder S Birring, lan D Pavord, Andrew J Wardlaw Institute for Lung Health, Leicester, UK Eosinophilic bronchitis (EB) is a common cause of chronic cough characterised by a sputum eosinophilia. In contrast to asthma there is no variable airflow obstruction or airway hyperresponsiveness. Eosinophilic airway inflammation in asthma is under the control ofTh2 cytokines, whereas the cytokine regulation of the inflammatory response in eosinophilic bronchitis is unknown. We hypothesised that the differences in airway pathophysiology between these two conditions may be related to cytokine expression by airway T-cells. From 10 subjects with EB, 9 with asthma and 9 normal controls 20ml of venous blood was taken and the subjects underwent a fibreoptic bronchoscopy and 180ml bronchoalveolar lavage (BAL) to the middle lobe. The peripheral blood mononuclear cell (PBMC) fraction was obtained by centrifugation on Ficoll. After washing PBMC and BAL cells were either stimulated with PMA, calcium ionophore and Brefeldin A or incubated in culture medium alone (resting) for 4hr at 37°C. The cells were fixed, incubated with CD3-F1TC/RPE and CD8-PerCP, permeabilised and labelled with IL-4-RPE and IFN-y-FITC or isotypic controls and analysed using three-colour flow cytometry. The median (range) % of stimulated CD4+ PBMC expressing IFN-y were increased in those subjects with EB 14 (2.8-52) and asthma 15 (7-30) compared to normals 3.3 (0.1-12) (Kruskal-Wallis p=0.024). Expression of 1L-4 was increased in EB and asthma compared to normals in both the resting (p=0.03) and stimulated (p=0.045) CD4+ BAL cells (Table). There were no between group differences in IL-4 expression in PBMC cells or IFN-yin BAL cells. In conclusion, increased Th2 cytokine expression by BAL T-cells is a feature of EB and asthma suggesting that they play a role in the airway inflammation observed in EB but that release of Th2 cytokines is not important in the development of disordered airway physiology in asthma.