Differential effects of simvastatin on IL-13-induced cytokine gene expression in primary mouse tracheal epithelial cells

Zeki, Amir A.; Thai, Phil; Kenyon, Nicholas J.; Wu, Reen

doi:10.1186/1465-9921-13-38

Cited by 38 publications

(36 citation statements)

References 47 publications

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“…In terms of biological plausibility, animal studies utilising allergic mouse models showed that statins have anti-inflammatory, anti-remodelling and immunomodulatory effects that attenuate airway hyper-reactivity and improve lung function 6 8 22. Although less work has been performed on mechanisms of action in lung resident cells, there is evidence of significant action in airway smooth muscle cells, fibroblasts, endothelial cells and epithelial cells in vitro 23 24. Given the pleiotropic biological effects, widespread use and reasonable safety record of statins, they may be a potential novel therapy for asthma.…”

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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“…The effects of statins on inflammation and remodelling have been studied mainly using simvastatin in animal models of allergic asthma. Simvastatin has been shown to inhibit epithelial IL-13-inducable pro-inflammatory cytokine production [230]. Ahmad et al [231] showed that simvastatin in a murine model resulted in reduction in inflammatory cell infiltration, mucus hypersecretion, epithelial injury, collagen deposition and AHR.…”

Section: Statins Metformin and Vitamin Dmentioning

confidence: 98%

Asthma Therapy and Its Effect on Airway Remodelling

Berair

Brightling

2014

Drugs

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Asthma remains a major health problem with significant morbidity, mortality and economic costs. In asthma, airway remodelling, which refers to all the microscopic structural changes seen in the airway tissue, has been recognised for many decades and remains one of the defining characteristics of the disease; however, it is still poorly understood. The detrimental pathophysiological consequences of some features of remodelling, like increased airway smooth muscle mass and subepithelial fibrosis, are well documented. However, whether targeting these by therapy would be beneficial is unknown. Although the prevailing thinking is that remodelling is an abnormal response to persistent airway inflammation, recent evidence, especially from studies of remodelling in asthmatic children, suggests that the two processes occur in parallel. The effects of asthma therapy on airway remodelling have not been studied extensively due to the challenges of obtaining airway tissue in the context of clinical trials. Corticosteroids remain the cornerstone of asthma therapy, and their effects on remodelling have been better studied than other drugs. Bronchial thermoplasty is the only asthma therapy to primarily target remodelling, although how it results in the apparent clinical benefits seen is not exactly clear. In this article we discuss the mechanisms of airway remodelling in asthma and review the effects of conventional and novel asthma therapies on the process.

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“…TGF-b can induce pulmonary fibrosis and impair lung function in mice [54]. Taken together these findings and those from other pre-clinical studies [34,55,56] suggest that atorvastatin could potentially attenuate airway remodelling in chronic asthma.…”

Section: Discussionmentioning

confidence: 58%

“…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]. IL-12p70 was reduced by atorvastatin and sCD40L by both atorvastatin and atorvastatin with ICS: both cytokines have been shown to be reduced by statins [35,36].…”

Section: Discussionmentioning

confidence: 98%