The chemotactic activity of sputum from patients with bronchiectasis.
Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.
Mikami
M
M
The Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
Llewellyn-Jones
C G
CG
Bayley
D
D
Hill
S L
SL
Stockley
R A
RA
D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D001565:Benzoates; D001987:Bronchiectasis / Q000503:physiopathology*; D001991:Bronchitis / Q000503:physiopathology; D002465:Cell Movement; D002630:Chemotactic Factors / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D007975:Leukotriene B4 / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009093:Mucus / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D015203:Reproducibility of Results; D013183:Sputum / Q000187:drug effects / Q000502:physiology*; D013492:Suppuration / Q000503:physiopathology
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D001565:Benzoates; D002630:Chemotactic Factors; D016209:Interleukin-8; C094099:LY 293111; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4