Evaluating budesonide efficacy in nasal polyposis and predicting the resistance to treatment

Abstract

Background: Cell resistance to glucocorticoids is a major problem in the treatment of nasal polyposis (NP). Objectives: The objectives of this study were to observe the effect of budesonide on the expression of IL-1β, TNF-α, granulocyte macrophage-colony stimulating factor, intercellular adhesion molecule (ICAM)-1, basic fibroblast growth factor, eotaxin-2, glucocorticoid receptor (GR)-α, GR-β, c-Fos and p65 in nasal polyps and to correlate their expression to clinical response. Methods: Biopsies from nasal polyps were obtained from 20 patients before and after treatment with topical budesonide. Clinical response to treatment was monitored by a questionnaire and nasal endoscopy. The mRNA levels of the studied genes were measured by real-time quantitative (RQ)-PCR. Results: There was a significant decrease in the expression of TNF-α (P<0.05), eotaxin-2 (P<0.05) and p65 (P<0.05) in NP after treatment. Poor responders to glucocorticoids showed higher expression of IL-1β (3.74 vs. 0.14; P<0.005), ICAM-1 (1.91 vs. 0.29; P<0.05) and p65 (0.70 vs. 0.16; P<0.05) before treatment. Following treatment, IL-1β (4.18 vs. 0.42; P<0.005) and GR-β (0.95 vs. 0.28; P<0.05) mRNA expression was higher in this group. Conclusion: Topical budesonide reduced the expression of TNF-α, eotaxin-2 and p65. Poor responders to topical budesonide exhibit higher levels of IL-1β, ICAM-1 and nuclear factor (NF)-κB at diagnosis and higher expression of both IL-1β and GR-β after treatment. These results emphasize the anti-inflammatory action of topical budesonide at the molecular level and its importance in the treatment of NP. Nevertheless, IL-1β, ICAM-1 and NF-κB may be associated with primary resistance to glucocorticoids in NP, whereas higher expression of GR-β in poor responders only after glucocorticoid treatment may represent a secondary drug resistance mechanism in this disease. © 2008 The Authors.