Glucocorticoid sensitivity of lipopolysaccharide-stimulated chronic obstructive pulmonary disease alveolar macrophages

Clin Exp Immunol. 2009 Oct;158(1):74-83. doi: 10.1111/j.1365-2249.2009.03986.x.


It has been reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD) display glucocorticoid (Gc) resistance. The Gc sensitivity of inflammatory mediators released by COPD macrophages may vary. The objective of this study was to identify Gc-insensitive inflammatory mediators produced by lipopolysaccharide (LPS)-stimulated alveolar macrophages from COPD patients. LPS-stimulated alveolar macrophages from 15 COPD patients, nine smokers (S) and nine healthy non-smokers (HNS) were stimulated with LPS with or without dexamethasone (100 and 1000 nM). Luminex and enzyme-linked immunosorbent assay were used to measure 23 inflammatory mediators. After LPS stimulation there were lower levels of inflammatory mediators in COPD patients and S compared to HNS. There was no difference between groups for the effects of dexamethasone at either concentration (P > 0.05 for all comparisons). Tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and growth-related oncogene (GRO)-alpha displayed the greatest sensitivity to dexamethasone in COPD patients, while IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) were the least sensitive. COPD macrophages have a reduced response to LPS. Gc sensitivity was similar in COPD macrophages compared to controls. We identify some Gc-insensitive cytokines, including GM-CSF, G-CSF and IL-8, that may be involved in the progression of airway inflammation in COPD patients.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Aged
  • Analysis of Variance
  • Bronchoalveolar Lavage Fluid / immunology
  • Cells, Cultured
  • Chemokine CXCL1 / analysis
  • Cytokines / analysis
  • Cytokines / immunology*
  • Dexamethasone / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glucocorticoids / pharmacology*
  • Granulocyte Colony-Stimulating Factor / analysis
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Humans
  • Interleukin-6 / analysis
  • Interleukin-8 / analysis
  • Lipopolysaccharides / pharmacology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology*
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Smoking / immunology
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / genetics


  • Adaptor Proteins, Signal Transducing
  • CXCL1 protein, human
  • Chemokine CXCL1
  • Cytokines
  • Glucocorticoids
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • MAPKAP1 protein, human
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Granulocyte Colony-Stimulating Factor
  • Dexamethasone
  • Granulocyte-Macrophage Colony-Stimulating Factor