Role for interleukin-6 in COPD-related pulmonary hypertension

Chest. 2009 Sep;136(3):678-687. doi: 10.1378/chest.08-2420. Epub 2009 Apr 6.


Background: Pulmonary artery remodeling triggered by alveolar hypoxia is considered the main mechanism of pulmonary hypertension (PH) in COPD patients. We hypothesized that the risk for PH in COPD is increased by an elevation in the proinflammatory cytokines interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and IL-1beta, as well as by specific genetic polymorphisms of these cytokines.

Methods: We assessed cytokine plasma levels and the polymorphisms G(-174)C IL-6, C(-511)T IL-1beta, and A(-2518)G MCP-1 in 148 COPD patients (recruited at two centers) with right heart catheterization data and 180 control subjects including smokers and nonsmokers. Human pulmonary artery smooth muscle cells (PA-SMCs) were cultured for IL-6 messenger RNA assays under normoxic and hypoxic conditions.

Results: Patients with PH (mean pulmonary artery pressure [PAP], >or= 25 mm Hg) had lower Pao(2) and higher plasma IL-6 values than those without PH; there were no differences in terms of pulmonary function test results or CT scan emphysema scores. Plasma IL-6 correlated with mean PAP (r = 0.39; p < 0.001) and was included in a multiple stepwise regression analysis, with mean PAP as the dependent variable. In patients with the IL-6 GG genotype, the mean PAP value was significantly higher and PH was more common than in CG or CC patients (adjusted odds ratio, 4.32; 95% confidence interval, 1.96 to 9.54). Exposure to 4 h of hypoxia led to an about twofold increase in IL-6 messenger RNA in cultured human PA-SMCs.

Conclusions: Inflammation, most likely involving IL-6, may contribute substantially to PH complicating COPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / genetics
  • Chi-Square Distribution
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression
  • Genotype
  • Humans
  • Hypertension, Pulmonary / blood*
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / genetics
  • Interleukin-1beta / blood
  • Interleukin-1beta / genetics
  • Interleukin-6 / blood*
  • Interleukin-6 / genetics
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Pulmonary Disease, Chronic Obstructive / complications*
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Regression Analysis
  • Respiratory Function Tests
  • Statistics, Nonparametric


  • CCL2 protein, human
  • Chemokine CCL2
  • Interleukin-1beta
  • Interleukin-6