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

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.

• Authors: Kittipong Maneechotesuwan, Sirinya Supawita, Kanda Kasetsinsombat, Adisak Wongkajornsilp, Peter J Barnes
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 121 Issue 1 Pg. 43-50 (Jan 2008) ISSN: 1097-6825 [Electronic] United States
• PMID: 18036645 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Anti-Asthmatic Agents
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Interleukin-10
• Kynurenine

Topics

• Administration, Inhalation
• Adrenal Cortex Hormones (administration & dosage, therapeutic use)
• Adult
• Anti-Asthmatic Agents (administration & dosage, therapeutic use)
• Asthma (drug therapy, immunology)
• Eosinophils (immunology)
• Female
• Humans
• Indoleamine-Pyrrole 2,3,-Dioxygenase (metabolism)
• Interleukin-10 (biosynthesis)
• Kynurenine
• Macrophages (immunology)
• Male
• Middle Aged
• Sputum (cytology, enzymology, immunology)
• Treatment Outcome
• Up-Regulation