Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase - 07/08/11
, Wuttichai Ekjiratrakul, MD a, Kanda Kasetsinsombat, MSc b, Adisak Wongkajornsilp, MD, PhD b, Peter J. Barnes, DSc, FRS c
Reprint requests: Kittipong Maneechotesuwan, MD, PhD, Division of Respiratory Disease and Tuberculosis, Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Rd, Bangkok 10700, Thailand.Abstract |
Background |
We have previously shown that inhaled corticosteroids activate indoleamine 2, 3-dioxygenase (IDO) activity through increased IL-10 secretion. Statins might enhance the anti-inflammatory effects of corticosteroids.
Objective |
In a double-blind study we added simvastatin to patients with mild asthma receiving a low dose of inhaled budesonide and evaluated sputum eosinophil counts, IL-10 secretion, and IDO activity, as well as their putative signaling pathways.
Methods |
After a 2-week run-in period without treatment, 50 asthmatic patients were treated with 200 μg of budesonide and randomly assigned to either 10 mg of simvastatin or matched placebo for 8 weeks. Inflammation was evaluated through eosinophil counts, secretory signaling molecules, and immunocytochemistry of macrophages in sputum.
Results |
Sputum eosinophil percentages were reduced significantly by the combined therapy with budesonide and simvastatin compared with budesonide alone (P = .02). Corticosteroids activated glucocorticoid-induced TNF receptor ligand, which induces activation of p52 through the noncanonical nuclear factor κB pathway, leading to the increased transcription and activation of IDO. Simvastatin enhanced corticosteroid-activated noncanonical nuclear factor κB–dependent induction of IDO by activating type I interferons and also enhanced the effect of corticosteroid on IL-10 release.
Conclusion |
A statin enhances the anti-inflammatory effect of an inhaled corticosteroid in asthma, and this was mediated through the alteration of IDO activity in macrophages.
El texto completo de este artículo está disponible en PDF.Key words : Indoleamine 2, 3-dioxygenase, kynurenine, inhaled corticosteroid, simvastatin, asthma
Abbreviations used : GITR, GITRL, ICS, IDO, IKK, NF-κB
Esquema
| Supported by the Siriraj Grant for Research Development and Medical Education of the Faculty of Medicine Siriraj Hospital, Mahidol University. |
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| Disclosure of potential conflict of interest: P. J. Barnes has received research support from GlaxoSmithKline, AstraZeneca, and Novartis. The rest of the authors have declared that they have no conflict of interest. |
Vol 126 - N° 4
P. 754 - octobre 2010 Regresar al número
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