Decreased indoleamine 2,3-dioxygenase activity and IL-10/IL-17A ratio in patients with COPD
- 1Division of Respiratory Disease and Tuberculosis, Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- 2Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- 3Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK
- Correspondence to Dr Kittipong Maneechotesuwan, Division of Respiratory Diseases and Tuberculosis, Mahidol University, 2 Prannok Street, Bangkok 10700, Thailand;
- Received 8 May 2012
- Revised 28 October 2012
- Accepted 21 November 2012
- Published Online First 19 December 2012
Rationale Indoleamine 2,3-dioxygenase (IDO) induces generation of regulatory T cells but suppresses Th17 cells and therefore might attenuate neutrophilic inflammation. The role of IDO in neutrophilic airway diseases such as chronic obstructive pulmonary disease (COPD) remains unknown. We evaluated IDO activity and expression and interleukin (IL)-10 and IL-17A levels in sputum from patients with COPD.
Methods IDO activity and cytokine concentrations in sputum supernatants from patients with COPD of varying severity and in smoking and non-smoking control subjects were determined by high-performance liquid chromatography and ELISA, respectively.
Results Patients with COPD had reduced sputum IDO activity and expression and IL-10 levels, with increased IL-17A, IL-6 and CXCL8 concentrations and sputum neutrophils. These changes were significantly correlated with disease severity. IDO activity was decreased, but to a lesser extent, in normal smokers compared with non-smoking controls.
Conclusions Patients with COPD have a progressive reduction in IDO activity with reversal of the balance between IL-10 and IL-17A, resulting in chronic airway neutrophilic inflammation.