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


CONCLUSIONS
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.
Maneechotesuwan
Kittipong
K
Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. sikmn@mahidol.ac.th
Supawita
Sirinya
S
Kasetsinsombat
Kanda
K
Wongkajornsilp
Adisak
A
Barnes
Peter J
PJ
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000627:therapeutic use; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D007737:Kynurenine; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D016896:Treatment Outcome; D015854:Up-Regulation
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016753:Interleukin-10; D007737:Kynurenine