Glucocorticosteroids rapidly inhibit allergen-induced expression of E-selectin in vitro in a mucosal model of allergic rhinitis.
BACKGROUND
Transendothelial migration of cells to sites of inflammation is a hallmark of the allergic reaction. The adhesion cascade involves the initial expression of the adhesion molecule E-selectin on endothelial cells. The aim of the study was to determine the efficacy of a 30-min preincubation of the glucocorticosteroids (GCS) fluticasone, prednisolone, and fluocortin butyl on allergen- and interleukin (IL)-1beta-induced E-selectin expression in allergic rhinitis.


METHODS
Freshly taken nasal inferior turbinate mucosa of 19 subjects with allergic rhinitis was cut into small cubes and preincubated for 30 min with prednisolone (n = 6), fluticasone (n = 5), and fluocortin butyl (n = 3) in different concentrations, followed by allergen exposure at a concentration of 1000 BU/ml for 1 and 2 h. Additionally, fluticasone-preincubated tissues were exposed to recombinant human rhIL-1beta (n = 5) at a concentration of 2 pg/ml. The expression of E-selectin was assessed by immunohistochemistry (APAAP technique) and computerized image evaluation.


RESULTS
In this model, E-selectin expression was significantly upregulated by allergen and rhIL- 1beta within 1 and 2 h. After 30-min preincubation with prednisolone and fluocortin butyl at drug concentrations of 10-8 mol/1, we found a significant (> or = 50%) reduction of the E-selectin expression after 1 and 2 h. Allergen-induced E-selectin expression was nearly abolished at concentrations of 10-5 (prednisolone) and 10-4 mol/l (fluocortin butyl). Fluticasone significantly inhibited E-selectin expression by > or = 50% at concentrations of 10-14 and 10-12 mol/l after 1 and 2 h, and abolished E-selectin induction at concentrations of 10-12 and 10-10 mol/l, respectively. Exposure of mucosal cubes to rhIL-lbeta (n = 5) also induced rapid upregulation of E-selectin expression, an effect which could be only partially suppressed by fluticasone preincubation at concentrations of 10-l0 mol/l.


CONCLUSIONS
Allergen-induced E-selectin expression is significantly and rapidly inhibited by GCS preincubation, fluticasone being more potent than prednisolone and fluocortin butyl. We suggest that this rapid effect is mainly indirect, possibly by inhibition of allergen-induced cytokine release.
Rudack
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ENT Department, University Hospital WWU Münster, Germany.
Bachert
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D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000494:pharmacology*; D000730:Androstadienes / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis*; D005448:Fluocortolone / Q000031:analogs & derivatives / Q000494:pharmacology; D000068298:Fluticasone; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D011058:Pollen; D011239:Prednisolone / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism*; D015854:Up-Regulation
D000485:Allergens; D000730:Androstadienes; D019040:E-Selectin; D005938:Glucocorticoids; D007375:Interleukin-1; D011994:Recombinant Proteins; D005448:Fluocortolone; C011824:fluocortin butyl ester; D011239:Prednisolone; D000068298:Fluticasone