Publication: Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase
Issued Date
2010-10-01
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ISSN
00916749
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2-s2.0-77957788255
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Allergy and Clinical Immunology. Vol.126, No.4 (2010)
Suggested Citation
Kittipong Maneechotesuwan, Wuttichai Ekjiratrakul, Kanda Kasetsinsombat, Adisak Wongkajornsilp, Peter J. Barnes Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase. Journal of Allergy and Clinical Immunology. Vol.126, No.4 (2010). doi:10.1016/j.jaci.2010.08.005 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/29192
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Title
Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase
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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. © 2010 American Academy of Allergy, Asthma & Immunology.