Intranasal fluticasone propionate inhibits recovery of chemokines and other cytokines in nasal secretions in allergen-induced rhinitis.
BACKGROUND
Allergen-induced nasal responses are associated with the recovery of proinflammatory mediators and cytokines. In recent years, a distinct group of chemotactic cytokines, chemokines, has been the focus of intense investigation as to their possible role in the pathogenesis of allergic diseases. Although corticosteroids have been known to be effective in the treatment of allergic diseases, their mechanism(s) of action has not been fully elucidated.


OBJECTIVE
To study the effect of topical fluticasone on the recovery of chemokines (IL-8, MIP-1 alpha, and RANTES) and other cytokines (IL-1 beta, IL-6, and GM-CSF) from nasal mucosa following allergen challenge. To correlate the improvement of rhinitis symptoms with cytokine levels during early-phase and late-phase allergic responses.


METHODS
A randomized, double-blind, placebo-controlled crossover study of fluticasone propionate, 200 micrograms q d, was performed in ten subjects with allergic rhinitis. Allergen challenge was administered after 1 week of treatment. Nasal secretions were collected immediately after challenge and during the late-phase reactions; symptom scores were recorded simultaneously. Nasal cytokines were assayed by specific ELISA.


RESULTS
The allergen challenge caused early-phase and late-phase allergic reactions and increased recovery of IL-1 beta, IL-6, IL-8, RANTES, MIP-1 alpha, and GM-CSF from the nasal mucosa. Intranasal fluticasone inhibited the allergen-induced increase in nasal symptoms. This was associated with decreases in cytokine recovery. A significant correlation was observed between decreases in cytokine levels and in symptom scores after treatment.


CONCLUSIONS
Our results suggest that treatment with topical fluticasone propionate inhibits allergen-induced nasal responses and the associated increase in the production/secretion of chemokines and other proinflammatory cytokines.
Weido
A J
AJ
Department of Internal Medicine, University of Texas Medical Branch at Galveston, USA.
Reece
L M
LM
Alam
R
R
Cook
C K
CK
Sim
T C
TC
D000287:Administration, Topical; D000485:Allergens / Q000009:adverse effects*; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018925:Chemokines / Q000378:metabolism*; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D008925:Mites / Q000276:immunology; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D009299:Nasal Provocation Tests; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*
D000485:Allergens; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D005938:Glucocorticoids; D000068298:Fluticasone