IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines

Background: IL-17 is a cytokine that has been reported to be produced by T lymphocytes. In vitro, IL-17 activates fibroblasts and macrophages for the secretion of GM-CSF, TNF-alpha, IL-1 beta, and IL-6. A number of these cyto kines are involved in the airway remodeling that is observed within the lun gs of asthmatic individuals. Objective: In this study, we investigated the expression of IL-17 in sputum and bronchoalveolar lavage specimens obtained from asthmatic subjects and from nonasthmatic control subjects. Methods: IL-17 was detected through use of immunocytochemistry, in situ hyb ridization, and Western blot. Bronchial fibroblasts were stimulated with IL -17, and cytokine production and chemokine production were detected through use of ELISA and RT-PCR. Results: Using immunocytochemistry, we demonstrated that the numbers of cel ls positive for IL-17 are significantly increased in sputum and bronchoalve olar lavage fluids of subjects with asthma in comparison with control subje cts (P < .001 and P < .005, respectively). We demonstrated that in addition to T cells, eosinophils in sputum and bronchoalveolar lavage fluids expres sed IL-17. Peripheral blood eosinophils were also positive for IL-17, and t he level of IL-17 in eosinophils purified from peripheral blood was signifi cantly higher in subjects with asthma than in controls (P < .01). To furthe r investigate the mechanism of action of IL-17 in vivo, we examined the eff ect of this cytokine on fibroblasts isolated from bronchial biopsies of ast hmatic and nonasthmatic subjects. IL-17 did enhance the production of profi brotic cytokines (IL-6 and IL-11) by fibroblasts, and this was inhibited by dexamethasone. Similarly, IL-17 increased the level of other fibroblast-de rived inflammatory mediators, such as the alpha -chemokines, IL-8, and grow th-related oncogene-oc. Conclusion: Our results, which demonstrate for the first time that eosinoph ils are a potential source of IL-17 within asthmatic airways, suggest that IL-17 might have the potential to amplify inflammatory responses through th e release of proinflammatory mediators such as alpha -chemokines.