Am. J. Respir. Crit. Care Med., Vol 151, No. 6, 06 1995, 1900-1906.
Cytokine immunoreactivity in seasonal rhinitis: regulation by a topical corticosteroid
P Bradding, IH Feather, S Wilson, ST Holgate and PH Howarth
University Medicine, Southampton General Hospital, United Kingdom.
Seasonal allergic rhinitis is characterized by the development of nasal
mucosal inflammation in response to natural allergen exposure, and is
prevented by the administration of topical corticosteroids. Interleukin- 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 inhibited by
corticosteroids. In this study we have therefore investigated the effect of
seasonal allergen exposure on the expression of immunoreactivity for IL-4,
IL-5, and IL-6 in nasal mucosal biopsies, and the effect of regular
prophylactic treatment with the topical corticosteroid, fluticasone
propionate. Following a nasal mucosal biopsy out of season, patients were
randomized double-blind to receive 6 wk of treatment during the pollen
season with either topical fluticasone nasal spray (200 micrograms daily)
or matching placebo. Each subject underwent a repeat nasal biopsy at the
end of the 6-wk treatment period. Seasonal increases in epithelial
eosinophils (p = 0.046), submucosal eosinophils (p = 0.001), and epithelial
mast cells (p = 0.055) occurred in the placebo--but not the
fluticasone-treated patients. Submucosal mast cell numbers 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 both mast cells and
eosinophils. Numbers of IL-4+ cells in the nasal submucosa were
significantly suppressed by treatment with fluticasone (p = 0.0003 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.(ABSTRACT TRUNCATED AT 250 WORDS)