Interleukin-6 and statin therapy: potential role in the management of COPD
© Young and Hopkins; licensee BioMed Central Ltd. 2013
Received: 2 April 2013
Accepted: 9 July 2013
Published: 17 July 2013
We read with interest the article by Ferrari and colleagues showing in a small prospective study of chronic obstructive pulmonary disease (COPD) patients that interleukin-6 (IL-6) is a useful biomarker predicting worsening exercise tolerance and greater mortality . We outline below the significance of this finding and its potential impact on the future management of COPD.
If these observations are true, then it follows that HMGCoA reductase inhibitors (statins) might be benefical in COPD patients through their powerful inhibition of IL-6-mediated systemic inflammation . Indeed, there is a large body of data from numerous observational studies showing that statin therapy reduces both morbidity and mortality in COPD including; reducing the rate of infective exacerbations, slowing the decline in FEV1, reducing mortality from pneumonia or infective exacerbations and improving exercise tolerance . This last clinical feature of COPD is very important as it significantly affects quality of life. In the first randomized control trial of statin therapy in COPD, exercise tolerance was improved by nearly 50% after 6 months of statin therapy compared to placebo . This improvement correlated with a significant reduction in serum IL-6 level (and CRP) but not lung function , suggesting IL-6-mediated systemic inflammation might be one of the primary determinants of poor exercise tolerance. Also of considerable importance, is the recent finding that elevated IL-6 or CRP levels are associated with increased risk of lung cancer , particularly in patients with COPD , and that lung cancer mortality is reduced by 17% with statin use [Supplementary Figure S11 from ref. . Together with the findings of the observational studies described above, these results make a strong argument for examining the role of statins as adjunct therapy to inhaler therapy in COPD (Figure 1) [8, 14]. This is particularly the case as current inhaler therapy in COPD is symptom-based, minimizing breathlessness and reducing exacerbations, while statin-based systemic therapy, inhibiting both systemic and pulmonary inflammation, appears to confer significant disease modifying benefits. It also argues in favor of investigating the utility of measuring serum IL-6 (or it’s surrogate CRP) in patients with COPD to target and monitor therapy [1–7, 14].
We conclude that the study of Ferrari and colleagues confirms earlier studies showing that outcomes in COPD are related to IL-6-mediated systemic inflammation . This observation not only provides the basis on which to better phenotype patients with COPD , but more importantly highlights the important potential utility of statin therapy as a significant disease-modifying therapy in COPD . This hypothesis requires urgent examination in clinical trials.
- Ferrari R, Tanni SE, Caram LMO, et al: Three-year follow-up of interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease. Thorax. 2013, 68: 691-694. 10.1186/1465-9921-14-24.View ArticleGoogle Scholar
- Pinto-Plata V, Casanova C, Mullerova H, et al: Inflammatory and repair serum biomarker pattern. Association to clinical outcomes in COPD. Respir Res. 2012, 13: 71-10.1186/1465-9921-13-71.PubMedPubMed CentralView ArticleGoogle Scholar
- Celli BR, Locantore N, Yates J, et al: Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012, 185: 1065-1072. 10.1164/rccm.201110-1792OC.PubMedView ArticleGoogle Scholar
- Agusti A, Edwards LD, Rennard SI, et al: Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. Plos One. 2012, 7: e3y483-View ArticleGoogle Scholar
- Man SFP, Connett JE, Anthonisen NR, et al: C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease. Thorax. 2006, 61: 849-853. 10.1136/thx.2006.059808.PubMedPubMed CentralView ArticleGoogle Scholar
- Dahl M, Vestbo J, Lange P, et al: C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007, 175: 250-255. 10.1164/rccm.200605-713OC.PubMedView ArticleGoogle Scholar
- Walter RE, Wilk JB, Larson MG, et al: Systemic inflammation and COPD: the Framingham Heart Study. Chest. 2008, 133: 19-25. 10.1378/chest.07-0058.PubMedView ArticleGoogle Scholar
- Young RP, Hopkins R, Eaton TE: Pharmacological actions of statins: potential utility in COPD. Eur Respir Rev. 2009, 118: 222-232.View ArticleGoogle Scholar
- Kuhn C, Homer RJ, Zhu Z, et al: Airway responsiveness and airway obstruction in transgenic mice: morphologic correlates in mice over-expressing IL-11 and IL-6 in the lung. Am J Respir Cell Mol Biol. 2000, 22: 289-295. 10.1165/ajrcmb.22.3.3690.PubMedView ArticleGoogle Scholar
- Lee T-M, Lin M-S, Chang N-C: Usefulness of C-reactive protein and interleukin-6 as predictors of outcomes in patients with chronic obstructive pulmonary disease receiving pravastatin. Am J Cardiol. 2008, 101: 530-535. 10.1016/j.amjcard.2007.09.102.PubMedView ArticleGoogle Scholar
- Young-Yin K, Young-Min K, Kyae HK, et al: High-sensitivity C-reactive protein levels and cancer mortality. Cancer Epidemiol Bio Prev. 2012, 21: 2076-2086. 10.1158/1055-9965.EPI-12-0611.View ArticleGoogle Scholar
- Thomsen M, Dahl M, Lange P, et al: Inflammatory biomarkers in chronic obstructive pulmonary disease. Am J Respir Crit Med. 2012, 186: 982-988. 10.1164/rccm.201206-1113OC.View ArticleGoogle Scholar
- Nielson SF, Nordestggard BG, Bojesin SE: Statin use and reduced cancer-related mortality. N Eng J Med. 2012, 367: 1792-1802. 10.1056/NEJMoa1201735.View ArticleGoogle Scholar
- McDonald VM, Higgins I, Woods LG, Gibson PG: Multidimensional assessment and tailored interventions for COPD: respiratory utopia or common sense?. Thorax. 2013, 10.1136/thoraxjnl-2012-202646.Google Scholar
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