Document Detail


Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase.
MedLine Citation:
PMID:  20920765     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kittipong Maneechotesuwan; Wuttichai Ekjiratrakul; Kanda Kasetsinsombat; Adisak Wongkajornsilp; Peter J Barnes
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2010-10-05     Completed Date:  2010-11-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  754-762.e1     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Division of Respiratory Disease and Tuberculosis, Department of Internal Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. sikmn@mahidol.ac.th
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MeSH Terms
Descriptor/Qualifier:
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:
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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