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The chemotactic activity of sputum from patients with bronchiectasis
M Mikami1, C G Llewellyn-Jones, D Bayley
1The Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
Abstract:
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.
Insights
Interleukin-8 (IL-8) and leukotriene-B4 (LTB4) are key chemoattractants in lung secretions. IL-8 is particularly important during acute exacerbations in chronic lung diseases, influencing polymorphonuclear neutrophil (PMN) recruitment.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Immunology
Background:
- Persistent polymorphonuclear neutrophil (PMN) recruitment contributes to chronic destructive lung diseases.
- The specific chemoattractants driving PMN migration in airways remain unclear.
Purpose of the Study:
- To investigate the roles of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) in the chemotactic activity of lung secretions.
- To determine the contribution of IL-8 and LTB4 to PMN recruitment in bronchiectasis.
Main Methods:
- Studied 59 sputum samples from 19 bronchiectasis patients.
- Used a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium) to inhibit chemoattractant activity.
- Correlated chemotactic activity with sputum appearance and response to antibiotic therapy.
Main Results:
- Chemotactic responses to IL-8 and LTB4 were additive and could be independently inhibited.
- Sputum appearance (mucoid to purulent) correlated with increased IL-8 contribution.
- Antibiotic therapy reduced chemotactic activity, primarily by decreasing IL-8 contribution.
- LTB4 contribution remained consistent across sputum types and clinical states.
Conclusions:
- LTB4 and IL-8 are significant chemotactic factors in lung secretions of patients with chronic lung disease.
- IL-8 plays a more critical role during acute exacerbations, impacting PMN recruitment.
- Findings may inform future therapeutic strategies for chronic destructive lung diseases.