Fluticasone propionate down-regulates IL-4 in the airways of asthmatic patients

Purpose: IL-4 is considered to play a key role in the pathogenesis of bronchial asthma. Fluticasone propionate is a potent new anti-inflammatory drug that is very effective in asthma treatment. The aims of this study were to investigate the IL-4 expression in the airways and to evaluate the effect of low dose inhaled Fluticasone propionate treatment on IL-4 expression. Methods: 23 mild to moderate stable asthmatic patients (4F, age range: 18 to 50 yrs, all non smokers) and 8 normal subjects (4F, age range: 22 to 29 yrs, all non smokers) were included in the study. In each subject bronchoscopy with BAL and bronchial biopsies were performed. 18 patients out of the asthmatic group started a 6 week low dose inhaled Fluticasone propionate treatment (250 mcg bd) in a placebo-controlled double-blind study and underwent the second bronchoscopy. IL-4 expression was evaluated on BAL cells and bronchial biopsies by immunochemistry methods. Results: IL-4 expression on BAL cells was significantly higher in asthmatics when compared to normal subjects (p<0.01). Both asthmatic and normal mucosa contained numerous cells staining positively for IL-4. Positive cells were present in both the submucosa and the epithelium. However, IL-4 expression was significantly higher in asthma patients when compared to normal controls (p<0.01). Fluticasone propionate treatment induced a reduction of the IL-4 expression on BAL cells (p<0.01) and bronchial mucosa (p<0.05). Conclusions: The present results reveal a spontaneous increase of IL-4 expression in the airways of asthmatic patients. These findings may have critical implications in the pathogenesis of allergic inflammation. Low dose inhaled Fluticasone propionate decreases IL-4 expression in the airways. Clinical Implications: Our results suggest that Fluticasone propionate can be considered very effective in asthma treatment by down-regulating key mechanisms of the allergic response.