Lipopolysaccharide-induced lung inflammation is inhibited by neutralization of GM-CSF

Eur J Pharmacol. 2007 Feb 28;557(2-3):230-5. doi: 10.1016/j.ejphar.2006.11.023. Epub 2006 Nov 14.


Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the pathogenesis of acute and chronic lung disease as a major regulator governing the functions of granulocyte and macrophage lineage populations. Chronic obstructive pulmonary disease (COPD) is a disease characterized by lung inflammation with accumulation of neutrophils and increased levels of pro-inflammatory cytokines including GM-CSF in the patient's lungs. We used intranasal administration of lipopolysaccharide (LPS) to mice to induce a disease that resembles COPD with pulmonary inflammation, neutrophil recruitment and release of pro-inflammatory mediators in the bronchoalveolar lavage fluid of the diseased mice. 2 h prior to LPS administration, mice were systemically treated with the murine GM-CSF neutralizing antibody mAb 22E9 per intraperitoneal injection. Intranasal challenge with LPS-induced an increase of total cell number and of neutrophils in the bronchoalveolar lavage fluid. Elevated levels of tumor necrosis factor alpha (TNF-alpha), keratinocyte cytokine and macrophage inflammatory protein-2 (MIP-2) were also observed at this time point. GM-CSF was no longer detectable in bronchoalveolar lavage fluid at 24 h due to its early expression with a peak reached 6 h after LPS challenge. Pretreatment of mice with GM-CSF neutralizing antibody dose-dependently inhibited the accumulation of neutrophils and reduced TNF-alpha and MIP-2 protein levels in bronchoalveolar lavage fluid. These data suggest that neutralization of GM-CSF may represent a novel treatment modality for lung inflammation and in particular for COPD.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Bronchoalveolar Lavage Fluid / cytology
  • Disease Models, Animal
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology
  • Pneumonia / chemically induced
  • Pneumonia / immunology*
  • Pneumonia / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism


  • Antibodies
  • Inflammation Mediators
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor