Tumor necrosis factor receptor 2 as a possible marker of COPD in smokers and ex-smokers

Int J Chron Obstruct Pulmon Dis. 2017 Jul 7:12:2015-2021. doi: 10.2147/COPD.S138558. eCollection 2017.

Abstract

Introduction: Oxidative stress and systemic inflammation are higher in smokers and patients with COPD; however, markers that may help differentiate between smokers and patients with COPD have not yet been identified. We hypothesized that tumor necrosis factor-alpha receptor (TNFR) and soluble form of the receptor for advanced glycation end products (sRAGE) can be indicators of COPD in asymptomatic patients.

Patients and methods: We evaluated 32 smokers (smoking history >10 pack-years), 32 patients with mild/moderate COPD (smokers and ex-smokers), and 32 never smokers. Concentrations of C-reactive protein (CRP), interleukin (IL)-6, TNFR1 and TNFR2, advanced glycation end products (AGEs), and the sRAGE were measured in serum.

Results: There were higher CRP and AGEs concentrations in smokers and in patients with COPD (P<0.001 and P=0.01, respectively) compared to controls, without statistical difference between smokers and patients with COPD. Concentrations of sRAGE, IL-6, and TNFR1 did not differ between study groups. TNFR2 was significantly higher in patients with COPD than in smokers (P=0.004) and controls (P=0.004), and the presence of COPD (P=0.02) and CRP (P=0.001) showed a positive association with TNFR2. Positive associations for smoking (P=0.04), CRP (P=0.03), and IL-6 (P=0.03) with AGEs were also found. The interaction variable (smoking × COPD) showed a positive association with IL-6.

Conclusion: Our data suggest that TNFR2 may be a possible marker of COPD in asymptomatic smokers and ex-smokers. Although smokers and patients with early COPD presented other increased systemic inflammation markers (eg, CRP) and oxidative stress (measured by AGEs), they did not differentiate smokers from COPD.

Keywords: chronic obstructive pulmonary disease; inflammation mediators; oxidative stress; smoking.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Asymptomatic Diseases
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Glycation End Products, Advanced / blood
  • Humans
  • Inflammation Mediators / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Oxidative Stress
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Receptor for Advanced Glycation End Products / blood
  • Receptors, Tumor Necrosis Factor, Type I / blood
  • Receptors, Tumor Necrosis Factor, Type II / blood*
  • Smokers*
  • Smoking / adverse effects
  • Smoking / blood*
  • Smoking Cessation*
  • Up-Regulation

Substances

  • AGER protein, human
  • Biomarkers
  • Glycation End Products, Advanced
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Receptor for Advanced Glycation End Products
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • TNFRSF1A protein, human
  • TNFRSF1B protein, human
  • C-Reactive Protein