Tumor necrosis factor alpha (TNF-α) autoregulates its expression and induces adhesion molecule expression in asthma

Abstract

Subjects with mild asthma underwent repeated low-dose allergen exposure and bronchial biopsies were examined for the expression of TNF-α and adhesion molecules. Bronchial biopsies from moderately severe asthmatics were then tested in an explant culture system to assess the effect of Der p and CDP-870, a TNF-α blocking pegylated-antibody Fab, on expression of TNF-α and adhesion molecules. Low-dose allergen challenge significantly upregulated sub-mucosal mast cells, TNF-α(+) cells, and VCAM. When bronchial explants were exposed to Der p and CDP 870 for 24h, CDP 870 caused a significant reduction in TNF-α release both at baseline and following stimulation with Der p allergen. The bronchial biopsies showed significant upregulation of TNF-α positive cells and ICAM-1 following exposure to Der p (p=0.03) and this was reduced in the presence of CDP-870. So, allergen exposure up-regulates TNF-α expression in asthma and down-stream targets, including adhesion molecules that contribute to airway inflammation.