Potential therapeutic role for statins in respiratory disease

Hothersall, Eleanor J

doi:10.1136/thx.2005.057976

Cited by 164 publications

(148 citation statements)

References 98 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…Through these mechanisms, statins reduce the expression of adhesion molecules, such as inter-cellular adhesion molecule 1, vascular cell adhesion molecule 1 and E-selectin, that are involved in the recruitment of inflammatory cells (neutrophils, monocytes and lymphocytes) from the circulation into the lungs. Statins also reduce the expression of chemokines, such as CCL2 and CXCL8, and MMPs, such as MMP-9, all of which are increased in COPD [182]. Some of these effects may be mediated via activation of peroxisome proliferator-activated receptors (PPAR)-a and -c and some via inhibition of NF-kB.…”

Section: Statinsmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

European Respiratory Journal

1,465

1,113

View full text Add to dashboard Cite

Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the ''spill-over'' of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

show abstract

Section: Statinsmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

European Respiratory Journal

1,465

1,113

View full text Add to dashboard Cite

show abstract

“…In recent years several studies have shown these positive eff ects of statins to be due both to their lipid lowering and antiinfl ammatory eff ect (Albert et al, 2001;Nissen et al, 2005;Ridker et al, 1998). Positive results in experimental trials have been obtained through the anti-infl ammatory effi cacy of statins in numerous respiratory disease models such as asthma, smoking-induced emphysema, pulmonary hypertension, IPF, acute lung injury and lung transplantation (Hothersall et al, 2006). Bleomycin (BLM)-induced pulmonary fi brosis is the most common pulmonary experimental model in rodents (Chua et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats

et al. 2012

View full text Add to dashboard Cite

Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-infl ammatory properties of statins. The purpose of this study was to evaluate the anti-infl ammatory eff ect of simvastatin on bleomycin (BLM)-induced pulmonary fi brosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buff ered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The eff ect of simvastatin on pulmonary fi brosis was studied by measurements of IL-13, PDGF, IFN-γ, TGF-β1 levels in bronchoalveolar lavage (BAL) fl uid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused signifi cant change in BAL fl uid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all). While LD simvastatin had no eff ect on cytokine levels, HD signifi cantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05) and TGF-β1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no eff ect on a BLMinduced pulmonary fi brosis model, while the high dose caused partial improvement in profi brotic cytokine levels.

show abstract

“…Statins have been proposed as potential novel treatments for respiratory diseases, including bronchial asthma (1,2). Reductions in chronic obstructive pulmonary disease morbidity and mortality, and improvements in lung function, have been attributed to statin use (1,(3)(4)(5).…”

mentioning

confidence: 99%

Simvastatin Inhibits Airway Hyperreactivity

Zeki

Franzi

Kenyon

2009

Am J Respir Crit Care Med

108

View full text Add to dashboard Cite

Rationale: Statin use has been linked to improved lung health in asthma and chronic obstructive pulmonary disease. We hypothesize that statins inhibit allergic airway inflammation and reduce airway hyperreactivity via a mevalonate-dependent mechanism. Objectives: To determine whether simvastatin attenuates airway inflammation and improves lung physiology by mevalonate pathway inhibition. Methods: BALB/c mice were sensitized to ovalbumin over 4 weeks and exposed to 1% ovalbumin aerosol over 2 weeks. Simvastatin (40 mg/kg) or simvastatin plus mevalonate (20 mg/kg) was injected intraperitoneally before each ovalbumin exposure. Measurements and Main Results: Simvastatin reduced total lung lavage leukocytes, eosinophils, and macrophages (P , 0.05) in the ovalbumin-exposed mice. Cotreatment with mevalonate, in addition to simvastatin, reversed the antiinflammatory effects seen with simvastatin alone (P , 0.05). Lung lavage IL-4, IL-13, and tumor necrosis factor-a levels were all reduced by treatment with simvastatin (P , 0.05). Simvastatin treatment before methacholine bronchial challenge increased lung compliance and reduced airway hyperreactivity (P 5 0.0001). Conclusions: Simvastatin attenuates allergic airway inflammation, inhibits key helper T cell type 1 and 2 chemokines, and improves lung physiology in a mouse model of asthma. The mevalonate pathway appears to modulate allergic airway inflammation, while the beneficial effects of simvastatin on lung compliance and airway hyperreactivity may be independent of the mevalonate pathway. Simvastatin and similar agents that modulate the mevalonate pathway may prove to be treatments for inflammatory airway diseases, such as asthma.

show abstract

Potential therapeutic role for statins in respiratory disease

Cited by 164 publications

References 98 publications

Systemic manifestations and comorbidities of COPD

Systemic manifestations and comorbidities of COPD

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats

Simvastatin Inhibits Airway Hyperreactivity

Contact Info

Product

Resources

About