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


METHODS
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.


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.
Beeh
Kai M
KM
Thoracic Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology & Medicine, London, UK.
Kornmann
Oliver
O
Buhl
Roland
R
Culpitt
Sarah V
SV
Giembycz
Mark A
MA
Barnes
Peter J
PJ
D000179:Acrylates / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000502:physiology*; D007975:Leukotriene B4 / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology* / Q000628:therapy; D011725:Pyridines / Q000494:pharmacology; D013183:Sputum / Q000166:cytology*
D000179:Acrylates; D000911:Antibodies, Monoclonal; D002630:Chemotactic Factors; D016209:Interleukin-8; D011725:Pyridines; C084128:SB 201146; D007975:Leukotriene B4