Trial Information

Study to Investigate the Role of TNF-alpha in Asthma Using Biopsy Explants and Primary Bronchial Epithelial Cell Cultures

Volunteers with moderately severe asthma will be recruited and carefully characterized in
terms of lung function, asthma symptom scores, medication usage and allergen sensitivity (by
blood and skin tests). If suitable, they will then be asked to withdraw their
corticosteroids for a week with careful monitoring of the symptoms and peak flows before
undergoing fibreoptic bronchoscopy as was carried out in the previous explant study.
Bronchial brushings and biopsies will be carried out as per standard technique used in
University medicine. Primary epithelial cell cultures will be established from bronchial
brushings and will be used for optimising the dose of anti TNF-alpha required for inhibition
of TNF-alpha induced responses. The biopsies will be placed in either culture medium alone,
allergen extract or allergen extract plus anti TNF-alpha antibody and cultured for 24 hours.
The biopsies will then be either snap frozen in liquid nitrogen for analysis of cytokines or
processed for immunohistochemical analysis. The supernatants from each study will be
recovered and analysed for cytokine (IL-5, IL-8, IL-13, MIP 1 alpha and RANTES) release by
ELISA.