Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal allergic rhinitis.
BACKGROUND
Glucocorticosteroids are effective in the treatment of allergic rhinitis, a disease characterized by a variety of symptoms, e.g. rhinorrhea and itching. The time course of symptomatic relief for allergic rhinitis by steroids has not been examined in detail to date, although the onset of steroid action is one of the main discriminations between genomic and nongenomic actions of steroids. We therefore investigated the time course of subjective and objective measures of nasal affection after steroid administration in patients with allergic rhinitis following specific allergen challenge.


METHODS
Six female and 18 male volunteers (median age 26 years) with a history of allergic rhinitis but currently free of symptoms were included in this randomized, placebo-controlled, double-blind, three-period crossover study. A single dose of either betamethasone (60 mg), methylprednisolone (400 mg) or placebo was given intravenously, 5 min after intranasal allergen provocation. After 10, 20, 60, 150 and 240 min, nasal itching and nasal obstruction were assessed using a standardized visual analogue scale. In addition, nasal airflow was measured by anterior rhinomanometry.


RESULTS
Nasal itching was markedly reduced following either of the two steroids within 10 min after administration of study drug. Itching was depressed by 38% following betamethasone (P<0.05) and by 18% following methylprednisolone (P=0.07) compared with placebo. Nasal airflow and nasal obstruction were not significantly altered by steroids during the first 2 h of the study. However, after 150 min, nasal airflow was 21% rsp. 19% higher after methylprednisolone and betamethasone (P<0.05) compared with placebo. After 240 min, nasal airflow was increased by 20% following betamethasone (P<0.05) and by 19% following methylprednisolone. Nasal obstruction was also beneficially affected by both steroids 150 and 240 min after administration compared with placebo (P<0.05 for both time points following betamethasone).


CONCLUSIONS
This study for the first time shows rapid in vivo effects of external glucocorticosteroids in humans. Itching, a pathophysiologically complex sensation, is favourably influenced by steroids within 10 min, therefore presumably via nongenomic mechanisms. Though no detailed mechanisms can be derived from this study, steroid interaction with receptors in the central nervous system may play an important role in mediating this effect.
Institute of Clinical Pharmacology, University of Heidelberg, Mannheim, Germany.
H-C
HC
Tillmann
B A
BA
Stuck
M
M
Feuring
K
K
Rossol-Haseroth
B M
BM
Tran
R
R
Lösel
B M
BM
Schmidt
K
K
Hörmann
M
M
Wehling
A
A
Schultz
D000485:Allergens / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001623:Betamethasone / Q000627:therapeutic use; D001985:Bronchial Provocation Tests / Q000379:methods; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D015508:Nasal Obstruction / Q000188:drug therapy; D009666:Nose / Q000187:drug effects; D011537:Pruritus / Q000188:drug therapy; D012123:Pulmonary Ventilation / Q000187:drug effects; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology; D025363:Rhinomanometry / Q000379:methods
D000485:Allergens; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D001623:Betamethasone; D008775:Methylprednisolone