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1.
Allergy ; 60(12): 1524-9, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16266385

ABSTRACT

BACKGROUND: Nasal lavage is a noninvasive method of obtaining inflammatory exudates following nasal allergen challenge (NAC), and permits cells and released mediators to be evaluated. OBJECTIVE: To determine the effects of a single dose of topical steroid on eosinophils and levels of chemokines and cytokines in nasal lavage fluid following NAC in patients with allergic rhinitis. METHODS: Patients with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season received either nasal budesonide (100 microg per nostril) or matched placebo before allergen challenge in a double blind two-way crossover design. A semi-automated mixed bead array system was employed to measure multiple chemokines and cytokines in small volumes (50 microl) of nasal lavage supernatants. RESULTS: Following NAC there was a rapid onset of nasal symptoms together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also detected following allergen challenge. A single dose of nasal budesonide caused a decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels of eotaxin, RANTES, IL-8 and MCP-1. CONCLUSION: This study suggests that a single dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13 responses following NAC. This model should be convenient for testing novel anti-inflammatory and immunoregulatory agents intended for the treatment of allergic rhinitis.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Budesonide/administration & dosage , Interleukin-13/antagonists & inhibitors , Interleukin-5/antagonists & inhibitors , Phleum/immunology , Pollen/immunology , Rhinitis, Allergic, Seasonal/drug therapy , Administration, Intranasal , Adult , Allergens/adverse effects , Allergens/immunology , Anti-Inflammatory Agents/therapeutic use , Budesonide/therapeutic use , Female , Humans , Interleukin-13/metabolism , Interleukin-5/metabolism , Male , Middle Aged , Nasal Lavage Fluid/immunology , Nasal Provocation Tests , Phleum/adverse effects , Pollen/adverse effects , Rhinitis, Allergic, Seasonal/etiology , Rhinitis, Allergic, Seasonal/metabolism , Rhinitis, Allergic, Seasonal/physiopathology , Treatment Outcome
2.
Clin Exp Allergy ; 35(12): 1608-14, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16393327

ABSTRACT

BACKGROUND: Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. OBJECTIVE: This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. METHODS: Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. RESULTS: Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected. CONCLUSION: Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Allergens , Androstadienes/administration & dosage , Interleukins/metabolism , Nasal Mucosa/immunology , Rhinitis, Allergic, Seasonal/immunology , Adrenal Cortex Hormones/therapeutic use , Adult , Analysis of Variance , Androstadienes/therapeutic use , Female , Fluticasone , Humans , Interleukin-13/analysis , Interleukin-13/metabolism , Interleukin-4/analysis , Interleukin-4/metabolism , Interleukin-5/analysis , Interleukin-5/metabolism , Interleukins/analysis , Male , Nasal Lavage Fluid/chemistry , Nasal Mucosa/drug effects , Nasal Provocation Tests , Poaceae , Pollen , Rhinitis, Allergic, Seasonal/drug therapy , Single-Blind Method
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