Kittipong ManeechotesuwanWuttichai EkjiratrakulKanda KasetsinsombatAdisak WongkajornsilpPeter J. BarnesMahidol UniversityNational Heart and Lung Institute2018-09-242018-09-242010-10-01Journal of Allergy and Clinical Immunology. Vol.126, No.4 (2010)009167492-s2.0-77957788255https://repository.li.mahidol.ac.th/handle/20.500.14594/29192Background: 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.Mahidol UniversityImmunology and MicrobiologyMedicineStatins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenaseArticleSCOPUS10.1016/j.jaci.2010.08.005