Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids

Maneechotesuwan, Kittipong; Supawita, Sirinya; Kasetsinsombat, Kanda; Wongkajornsilp, Adisak; Barnes, Peter J.

doi:10.1016/j.jaci.2007.10.011

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 121, Issue 1 , Pages 43-50, January 2008

Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids

Kittipong Maneechotesuwan, MD, PhD
- Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Reprint requests: Kittipong Maneechotesuwan, MD, PhD, Division of Respiratory Disease and Tuberculosis, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok St, Bangkok 10700, Thailand.
Sirinya Supawita, MD
- Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Kanda Kasetsinsombat, MSc
- Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Adisak Wongkajornsilp, MD, PhD
- Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Peter J. Barnes, DSc, FRCP
- National Heart and Lung Institute, Imperial College, London, United Kingdom

Received 8 May 2007; received in revised form 1 October 2007; accepted 10 October 2007. published online 26 November 2007.

Background

Indoleamine-2, 3-dioxygenase (IDO), a tryptophan-degrading enzyme, plays a key role in the regulation of T-lymphocyte function. IDO inhibits eosinophilic inflammation in a murine asthma model, but little is known about its role in asthmatic patients or the effects of corticosteroids on this key regulatory enzyme.

Objective

We studied IDO activity and the effect of inhaled corticosteroids (ICSs) in patients with asthma and how this correlated with eosinophilic inflammation.

Methods

After a 1-week run-in period on no therapy, 34 asthmatic patients were treated with only short-acting β₂-agonists as required or an ICS or an ICS in combination with a long-acting β₂-agonist, which were required for asthma control, and the treatment was continued for a further 4 weeks. Each patient underwent sputum induction at the end of the run-in and treatment periods. Sputum supernatant specimens were analyzed for IDO activity and kynurenine concentrations by using HPLC.

Results

All patients with mild intermittent and mild-to-moderate persistent asthma had low baseline IDO activity in induced sputum compared with that seen in age-matched nonasthmatic subjects. The IDO activity was markedly enhanced by either ICS (P = .03) or ICS/long-acting β₂-agonist (P < .0001) treatment, and this increase negatively correlated with sputum eosinophils but was positively associated with an increase in IL-10–positive macrophages.

Conclusion

ICSs might exert their anti-inflammatory activity in asthmatic airways, at least in part, through the upregulation of IDO activity associated with increased IL-10 secretion from macrophages.

Key words: Asthma, indoleamine-2, 3-dioxygenase, kynurenine, inhaled corticosteroid, IL-10

Abbreviations used: DTT, Dithiothreitol, ICS, Inhaled corticosteroid, IDO, Indoleamine-2, 3-dioxygenase, LABA, Long-acting β₂-agonist