Statins enhance the effects of corticosteroids on the balance between regulatory T cells and Th17 cells

Maneechotesuwan, Kittipong; Kasetsinsombat, Kanda; Wamanuttajinda, Valla; Wongkajornsilp, Adisak; Barnes, Peter J.

doi:10.1111/cea.12067

Cited by 53 publications

(41 citation statements)

References 59 publications

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“…In their first study, they reported that 10 mg of simvastatin in addition to inhaled budesonide enhanced the anti-inflammatory effects of budesonide (eg, sputum eosinophils), by mechanisms involving alterations in indoleamine 2,3-dioxygenase and interleukin-10 release. In follow-up work, using an in vitro model of asthma, Maneechotesuwan et al 36 also found that the combination of simvastatin and fluticasone augments regulatory T cell (Treg) and Th17 responses to suppress airway inflammation in asthma. Because severe asthma has been linked to Th17 cell and neutrophilic inflammation,37 these findings suggest that statins may alter the biology relevant to severe asthma rather than milder disease.…”

Section: Discussionmentioning

confidence: 99%

Statin use and asthma control in patients with severe asthma

et al. 2013

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ObjectivesWe hypothesised that severe asthmatics taking a statin drug, in addition to inhaled corticosteroids/long-acting β-agonist inhaler therapy, would have better asthma symptom control and improved lung function compared to their controls.Study designA retrospective, cross-sectional study of 165 patients with severe asthma seen from 2001–2008. Hierarchical linear and logistic regression models were used for modelling fitting.SettingUniversity of California, Davis Medical Center (Sacramento, California, USA). Academic, single-centre, severe asthma subspecialty clinic.Participants612 screened, 223 eligible and 165 adult patients were included in the final study (N=165; 31 statin users and 134 non-users).Primary and secondary outcome measuresThe primary endpoint was asthma control as measured by the Asthma Control Test (ACT). The secondary endpoints included lung function, symptoms and the need for corticosteroid burst and peripheral eosinophil count.ResultsAt baseline, statin users compared to non-users were older, had lower lung function (FEV1% predicted, FEV1, forced vital capacity and FEF25–75%) and had a higher prevalence of comorbid conditions. Statin use was associated with more aspirin and ipratropium inhaler use than in non-users. Patients in both groups were obese (body mass index ≥ 30). Statin users had better asthma symptom control compared to non-users (higher adjusted mean ACT score by 2.2±0.94 points, p<0.02). Median statin use was for 1 year. There were no statistically significant differences in lung function, corticosteroid or rescue bronchodilator use or peripheral eosinophilia between the two groups.ConclusionsIn our severe asthma referral population, statin users already taking inhaled controller therapy achieved better asthma control compared to non-users. The implications of this study is that patients with severe asthma could potentially benefit from added statin treatment. Because our study population was on average obese, the obese severe asthmatic may be a viable asthma subphenotype for further studies. Prospective randomised clinical trials evaluating the safety and efficacy of statins in severe asthma are warranted.

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Section: Discussionmentioning

confidence: 99%

Statin use and asthma control in patients with severe asthma

et al. 2013

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“…For example, smoking asthmatics may also benefit from statins, but the specific sputum inflammatory cell subtypes relevant to severe asthma have not been fully characterized [53,57]. Overall, both animal and human data suggest that combined statin and corticosteroid therapy has additive and possibly synergistic anti-inflammatory effects in the lungs, something that would be very beneficial in severe asthma [54,90,91]. …”

Section: The Mevalonate Pathway Statins and Relevance To Asthmamentioning

confidence: 99%

Innovations in asthma therapy: is there a role for inhaled statins?

Zeki

Elbadawi-Sidhu

2018

Expert Review of Respiratory Medicine

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Introduction Asthma manifests as chronic airflow obstruction with persistent inflammation and airway hyperresponsiveness. The immunomodulatory and anti-inflammatory properties of the HMG-CoA reductase (HMGCR) inhibitors (a.k.a. statins), suggest a therapeutic role in chronic inflammatory lung diseases. However, despite positive laboratory investigations and promising epidemiological data, clinical trials using statins for the treatment of asthma have yielded conflicting results. Inadequate statin levels in the airway compartment could explain these findings. Areas covered HMGCR is in the mevalonate (MA) pathway and MA signaling is fundamental to lung biology and asthma. This article will discuss clinical trials of oral statins in asthma, review lab investigations relevant to the systemic versus inhaled administration of statins, address the advantages and disadvantages of inhaled statins, and answer the question: is there a role for inhaled statins in the treatment of asthma? Expert commentary If ongoing investigations show that oral administration of statins has no clear clinical benefits, then repurposing statins for delivery via inhalation is a logical next step. Inhalation of statins bypasses first-pass metabolism by the liver, and therefore, allows for delivery of significantly lower doses to the airways at greater potency. Statins could become the next major class of novel inhalers for the treatment of asthma.

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“…In an animal allergic model atorvastatin reduced IL-10 [31] although others have reported that atorvastatin increased IL-10 concentration in bronchoalveolar lavage fluid and in splenocytes in allergic mice models [32]. Furthermore the enhancing effects of simvastatin on fluticasone effects are thought to be mediated through the up-regulation of indoleamine 2, 3-dioxygenase and IL-10, together with down-regulation of IL-6 and IL-23 expression in myeloid dendritic cells [33]. Atorvastatin has no effect on IL-10 expression on primary mouse tracheal epithelial cells [34].…”

Section: Discussionmentioning

confidence: 99%