| Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase. | |
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MedLine Citation:
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PMID: 20920765 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Kittipong Maneechotesuwan; Wuttichai Ekjiratrakul; Kanda Kasetsinsombat; Adisak Wongkajornsilp; Peter J Barnes |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of allergy and clinical immunology Volume: 126 ISSN: 1097-6825 ISO Abbreviation: J. Allergy Clin. Immunol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-05 Completed Date: 2010-11-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1275002 Medline TA: J Allergy Clin Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 754-762.e1 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Division of Respiratory Disease and Tuberculosis, Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. sikmn@mahidol.ac.th |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Anti-Inflammatory Agents / administration & dosage*, therapeutic use Asthma / drug therapy* Budesonide / administration & dosage*, therapeutic use Double-Blind Method Drug Synergism Drug Therapy, Combination Enzyme Induction Female Humans Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis*, drug effects* Macrophages / drug effects, enzymology Male Middle Aged Simvastatin / administration & dosage*, therapeutic use Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 51333-22-3/Budesonide; 79902-63-9/Simvastatin; EC 1.13.11.42/Indoleamine-Pyrrole 2,3,-Dioxygenase |
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