CYTOKINE IMMUNOREACTIVITY IN SEASONAL RHINITIS - REGULATION BY A TOPICAL CORTICOSTEROID

Seasonal allergic rhinitis is characterized by the development of nasa l mucosal inflammation in response to natural allergen exposure, and i s prevented by the administration of topical corticosteroids. Interleu kin-4 (IL-4), IL-5, and IL-6 may have important roles in this process, and in vitro the gene transcription for each of these cytokines is in hibited by corticosteroids. in this study we have therefore investigat ed the effect of seasonal allergen exposure on the expression of immun oreactivity for IL-4, IL-5, and IL-6 in nasal mucosal biopsies, and th e effect of regular prophylactic treatment with the topical corticoste roid, fluticasone propionate. Following a nasal mucosal biopsy out of season, patients were randomized double-blind to receive 6 wk of treat ment during the pollen season with either topical fluticasone nasal sp ray (200 mu g daily) or matching placebo. Each subject underwent a rep eat nasal biopsy at the end of the 6-wk treatment period. Seasonal inc reases in epithelial eosinophils (p = 0.046), submucosal eosinophils ( p = 0.001), and epithelial mast cells(p = 0.055) occurred in the place bo-but not the fluticasone-treated patients. Submucosal mast cell numb ers did not change in either group. Immunoreactivity for IL-4 and IL-6 was localized predominantly to mast cells while IL-5 was found in bot h mast cells and eosinophils. Numbers of IL-4(+) cells in the nasal su bmucosa were significantly suppressed by treatment with fluticasone (p = 0.003 for monoclonal antibody [mAb] 3H4, p = 0.041 for mAb 4D9). In contrast, fluticasone treatment failed to influence the number of IL- 5 and IL-6 immunoreactive cells. Thus topical administration of flutic asone propionate suppresses IL-4 expression in the nasal submucosa dur ing the pollen season, which may contribute to the anti-inflammatory e ffects of this form of treatment.