期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 126, 期 4, 页码 754-U121出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2010.08.005
关键词
Indoleamine 2, 3-dioxygenase; kynurenine; inhaled corticosteroid; simvastatin; asthma
资金
- Research Development and Medical Education of the Faculty of Medicine Siriraj Hospital, Mahidol University
- GlaxoSmithKline
- AstraZeneca
- Novartis
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 mu g 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 kappa B pathway, leading to the increased transcription and activation of IDO. Simvastatin enhanced corticosteroid-activated noncanonical nuclear factor kappa B-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. (J Allergy Clin Immunol 2010;126:754-62.)
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