Asthma and lower airway diseaseStatins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase
Section snippets
Patients
Nonsmoking patients with stable asthma were defined according to American Thoracic Society criteria and were treated with less than 1,000 μg/d beclomethasone dipropionate or an equivalent ICS. None of the patients had received oral corticosteroids within 3 months before the study. Subjects had a baseline FEV1 of 60% or greater of predicted value and demonstrated 12% or greater reversibility of FEV1 after therapy with nebulized salbutamol (2.5 mg) and a provocative concentration of methacholine
Patients
Of a total of 63 screened patients, 50 fulfilled the entry requirements and were randomized into either the simvastatin tablet group (n = 25) or the placebo group (n = 25; Fig 1, B, and Table I). Forty-seven patients completed the treatment phase, and 3 patients discontinued the study before completion, 3 in the simvastatin arm (2 were unable to provide adequate sputum and 1 had missing final lung function test data).
Simvastatin increases the anti-inflammatory effect of ICSs on eosinophilic airway inflammation in asthmatic patients
During the run-in off-treatment period, all patients had eosinophilic airway
Discussion
We conceived this randomized controlled study to verify whether a statin enhances the anti-inflammatory effects of an ICS in asthma. Here we have demonstrated that simvastatin increases the anti-inflammatory effect of inhaled budesonide in suppressing eosinophilic airway inflammation in asthmatic patients and that this is mediated through the activation of IDO through 2 distinct but interacting molecular pathways. First, corticosteroids induce IDO activation through the GITRL-associated
References (22)
- et al.
Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids
J Allergy Clin Immunol
(2008) - et al.
The two NF-kappaB activation pathways and their role in innate and adaptive immunity
Trends Immunol
(2004) - et al.
Anti-inflammatory mechanism of simvastatin in mouse allergic asthma model
Eur J Pharmacol
(2007) - et al.
Loss of control of asthma following inhaled corticosteroid withdrawal is associated with increased sputum interleukin-8 and neutrophils
Chest
(2007) - et al.
Effects of montelukast compared to double dose budesonide on airway inflammation and asthma control
Respir Med
(2007) - et al.
Interferon induces NF-kappa B-inducing kinase/tumor necrosis factor receptor-associated factor-dependent NF-kappa B activation to promote cell survival
J Biol Chem
(2005) - et al.
IDO expression by dendritic cells: tolerance and tryptophan catabolism
Nat Rev Immunol
(2004) - et al.
Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase
Science
(2002) - et al.
Inhibition of T cell proliferation by macrophage tryptophan catabolism
J Exp Med
(1999) - et al.
Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy
Nat Immunol
(2001)
Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites
J Exp Med
Cited by (0)
Supported by the Siriraj Grant for Research Development and Medical Education of the Faculty of Medicine Siriraj Hospital, Mahidol University.
Disclosure of potential conflict of interest: P. J. Barnes has received research support from GlaxoSmithKline, AstraZeneca, and Novartis. The rest of the authors have declared that they have no conflict of interest.