Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease

BackgroundPast studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers.MethodsA cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry.ResultsIL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02]. CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years.ConclusionsThe systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients.Trial registrationNo.:NCT00605540

[1]  S. Tanni,et al.  Three-year follow-up study of respiratory and systemic manifestations of chronic obstructive pulmonary disease. , 2011, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[2]  A. Ionescu,et al.  Inflammatory response and body composition in chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[3]  S. Tanni,et al.  Smoking status and tumor necrosis factor-alpha mediated systemic inflammation in COPD patients , 2010, Journal of Inflammation.

[4]  Ciro Casanova,et al.  The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. , 2004, The New England journal of medicine.

[5]  J. Soriano,et al.  C-reactive protein in patients with COPD, control smokers and non-smokers , 2005, Thorax.

[6]  M. Rincón,et al.  Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. , 2012, Trends in immunology.

[7]  Predictors of mortality in elderly subjects with obstructive airway disease: the PILE score. , 2010, Annals of epidemiology.

[8]  S. Rubin,et al.  Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects , 2005, Thorax.

[9]  B. Celli,et al.  C-reactive protein levels and survival in patients with moderate to very severe COPD. , 2008, Chest.

[10]  Courtney Crim,et al.  Persistent Systemic Inflammation is Associated with Poor Clinical Outcomes in COPD: A Novel Phenotype , 2012, PloS one.

[11]  F. Martinez,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. , 2007, American journal of respiratory and critical care medicine.

[12]  T. Kishimoto Interleukin-6: from basic science to medicine--40 years in immunology. , 2005, Annual review of immunology.

[13]  W. Bailey,et al.  Editorial: Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 Guidelines for COPD, Including COVID-19, Climate Change, and Air Pollution , 2023, Medical science monitor : international medical journal of experimental and clinical research.

[14]  J. Soriano,et al.  C-reactive protein in patients with COPD, control smokers and non-smokers: Thorax 2006;61:23–8 , 2006 .

[15]  Olaf Holz,et al.  Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. , 2011, Chest.

[16]  Michael E. Miller,et al.  Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[17]  J. Gold,et al.  Validation of a combined comorbidity index. , 1994, Journal of clinical epidemiology.

[18]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[20]  D. Sin,et al.  Interleukin-6: a red herring or a real catch in COPD? , 2008, Chest.

[21]  John R Hurst,et al.  Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease. , 2006, American journal of respiratory and critical care medicine.

[22]  S. Bojesen,et al.  C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease. , 2007, American journal of respiratory and critical care medicine.

[23]  Ciro Casanova,et al.  Inflammatory and repair serum biomarker pattern. Association to clinical outcomes in COPD , 2012, Respiratory Research.

[24]  Satoko Nakamura,et al.  Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients: comparison with C-reactive protein. , 2011, Cytokine.

[25]  L. Fried,et al.  Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars. , 2012, The journals of gerontology. Series A, Biological sciences and medical sciences.

[26]  R. J. Shephard,et al.  Physical Activity Is the Strongest Predictor of All-Cause Mortality in Patients With COPD: A Prospective Cohort Study , 2012 .

[27]  T. Kishimoto,et al.  The biology of interleukin-6. , 1989, Blood.

[28]  Dave Singh,et al.  The repeatability of interleukin-6, tumor necrosis factor-α, and C-reactive protein in COPD patients over one year , 2009, International journal of chronic obstructive pulmonary disease.

[29]  E. Wouters,et al.  Raised CRP levels mark metabolic and functional impairment in advanced COPD , 2005, Thorax.

[30]  E. Benjamin,et al.  Systemic inflammation and COPD: the Framingham Heart Study. , 2008, Chest.

[31]  K. Rabe Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease , 2011, British journal of pharmacology.

[32]  R. Garrod,et al.  The relationship between inflammatory markers and disability in chronic obstructive pulmonary disease (COPD). , 2007, Primary care respiratory journal : journal of the General Practice Airways Group.

[33]  L. Edwards,et al.  Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. , 2012, American journal of respiratory and critical care medicine.

[34]  A Senthilselvan,et al.  Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis , 2004, Thorax.

[35]  Fabio Pitta,et al.  Validação do Modified Pulmonary Functional Status and Dyspnea Questionnaire e da escala do Medical Research Council para o uso em pacientes com doença pulmonar obstrutiva crônica no Brasil , 2008 .