Neutrophil chemotactic activity of sputum from patients with COPD: role of interleukin 8 and leukotriene B4

Chest. 2003 Apr;123(4):1240-7. doi: 10.1378/chest.123.4.1240.


Study objectives: Neutrophilic inflammation is a major feature of COPD. Several factors in bronchial secretions have been identified as chemoattractants for neutrophils. The present study was designed to assess the contribution of interleukin (IL)-8 and leukotriene B(4) (LTB(4)) to neutrophil chemotaxis evoked by sputum obtained from patients with established COPD.

Design: Sputum supernatant of 20 patients with COPD was used as chemoattractant in a 96-well chemotaxis chamber, with subsequent quantification of migrated cells by a luminescence assay. The contribution of IL-8 and LTB(4) to chemotaxis was determined by addition of a neutralizing antibody and a selective receptor antagonist, respectively.

Measurements and results: COPD sputum caused neutrophil chemotaxis in a concentration-dependent manner, with a maximum response evoked with a 10-fold dilution of the original sample. Pretreatment of sputum or neutrophils with either an anti-IL-8 antibody or the LTB(4) antagonist, SB 201146, led to a concentration-dependent inhibition of sputum-induced neutrophil chemotaxis, with a maximum suppression (mean +/- SEM) of 29.2 +/- 4.9% (p < 0.001) from baseline by 100 ng/mL of anti-IL-8 antibody, and 45.6 +/- 7% (p < 0.02) by 10 micro mol/L of SB 201146. The combination of the anti-IL-8 antibody and SB 201146 inhibited neutrophil chemotaxis, but this was not significantly greater than the effect of SB 201146 or anti-IL-8 alone.

Conclusions: These data confirm the importance of IL-8 and LTB(4) as chemoattractants for neutrophils in bronchial secretions from patients with COPD, and suggest that specific inhibitors may have therapeutic potential in COPD.

MeSH terms

  • Acrylates / pharmacology
  • Antibodies, Monoclonal
  • Chemotactic Factors / physiology*
  • Chemotaxis, Leukocyte*
  • Humans
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / physiology*
  • Leukotriene B4 / physiology*
  • Neutrophils / physiology
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Pulmonary Disease, Chronic Obstructive / therapy
  • Pyridines / pharmacology
  • Sputum / cytology*


  • Acrylates
  • Antibodies, Monoclonal
  • Chemotactic Factors
  • Interleukin-8
  • Pyridines
  • SB 201146
  • Leukotriene B4