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J Allergy Clin Immunol. 2008 Jan;121(1):43-50. Epub 2007 Nov 26.

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

Author information

1
Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. sikmn@mahidol.ac.th

Abstract

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 beta(2)-agonists as required or an ICS or an ICS in combination with a long-acting beta(2)-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 beta(2)-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.

PMID:
18036645
DOI:
10.1016/j.jaci.2007.10.011
[Indexed for MEDLINE]

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