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 B4 (LTB4) 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 LTB4 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 LTB4 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 μmol/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 LTB4 as chemoattractants for neutrophils in bronchial secretions from patients with COPD, and suggest that specific inhibitors may have therapeutic potential in COPD.