Effect of intranasal fluticasone on cellular infiltration, endothelial adhesion molecule expression, and proinflammatory cytokine mRNA in nasal polyp disease

Background: Nasal polyp (NP) disease demonstrates a gradual response to treatment with intranasal steroids. We hypothesized that various inflammatory features that promote NP eosinophilia would show a differential sensitivity to treatment with intranasal fluticasone. Objectives: We conducted a double-blind, placebo-controlled trial of 4 weeks of intranasal fluticasone propionate or matching placebo to assess their effectiveness in reducing NP inflammatory cells, expression of endothelial vascular cell adhesion molecule (VCAM)-1 and P-selectin, and expression of cytokines involved in induction of a group of adhesion molecules (ie, IL-4, IL-13, TNF-alpha, and IL-1 beta). Methods: Twenty subjects (9 women and II men) with severe chronic sinusitis and NP were studied. Systemic and intranasal steroids were withheld for a minimum of I month and 2 weeks, respectively, before the study. Biopsy specimens of NPs were obtained 1 week before and 4 weeks after treatment with intranasal fluticasone 100 mu g or placebo per nostril administered twice daily. Biopsy specimens were snap frozen for immunostaining or fixed in paraformaldehyde for in situ hybridization. Pretreatment to posttreatment results were analyzed with Wilcoxon's signed-rank test. Results: Fluticasone treatment significantly reduced NP eosinophilia (P = .02) and CD4(+) T lymphocytes (P = .02). Eosinophils expressing the marker EG2 were more significantly reduced (P = .007). Fluticasone also reduced the expression of P-selectin (P = .005) and the number of IL-4 and IL-13 mRNA(+) cells (P = .02 and .05, respectively). In contrast, fluticasone did not significantly reduce expression of endothelial VCAM-1 or the number of TNF-alpha or IL-1 beta mRNA(+) cells in the polyps. Conclusions: We conclude that intranasal fluticasone reduced NP inflammation but that expression of proinflammatory cytokines and endothelial VCAM-1 were relatively unaffected by fluticasone treatment. These latter inflammatory features may contribute to the persistence of NP disease despite intranasal steroid treatment.