Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase

J Allergy Clin Immunol. 2010 Oct;126(4):754-762.e1. doi: 10.1016/j.jaci.2010.08.005.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / therapeutic use
  • Asthma / drug therapy*
  • Budesonide / administration & dosage*
  • Budesonide / therapeutic use
  • Double-Blind Method
  • Drug Synergism
  • Drug Therapy, Combination
  • Enzyme Induction
  • Female
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / drug effects*
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Male
  • Middle Aged
  • Simvastatin / administration & dosage*
  • Simvastatin / therapeutic use
  • Treatment Outcome


  • Anti-Inflammatory Agents
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Budesonide
  • Simvastatin