Inhibition of Mediator Release in Allergic Rhinitis by Pretreatment with Topical Glucocorticosteroids

Patients with allergic rhinitis often have immediate symptoms after antigen challenge (the early-phase response), followed several hours later by a recurrence of symptoms (the late-phase response). Systemic glucocorticosteroids are known to inhibit the late-phase but not the early-phase response. We studied the effect of one week of pretreatment with topical (rather than systemic) glucocorticosteroids on the response to nasal challenge with antigen in a double-blind, randomized, placebo-controlled crossover study of 13 allergic patients who had previously had a dual response to nasal challenge. The patients were challenged with three 10-fold increments of allergen, producing an early response, and were then followed for 11 hours, encompassing the late response, before they were rechallenged with the lowest dose of allergen. We monitored their responses by means of symptom scores and measurements of the levels of histamine, tosyl-L-arginine methyl ester (TAME)-esterase activity, and kinins in nasal lavages. Topical glucocorticosteroids significantly reduced both the symptoms and the levels of histamine, TAME-esterase activity, and kinins in the early, late, and rechallenge allergic reactions. The fact that, in contrast to treatment with systemic glucocorticosteroids, prolonged pretreatment with topical glucocorticosteroids inhibited the early-phase response to antigen suggests that the route and duration of administration affect the mechanisms of action of the steroids. We conclude that inhibition of the early-phase as well as the late-phase response by topical glucocorticosteroids may provide an advantage over treatment with systemic glucocorticosteroids in patients with allergic rhinitis. (N Engl J Med 1987; 316:1506–10.), SYSTEMICALLY administered glucocorticosteroids, which are potent agents in the treatment of allergic disease, affect the late but not the early phase of the biphasic response to antigen challenge, as shown in numerous studies involving the lungs and skin in animals and humans.^{1 2 3 4} For example, in a nasal-challenge study, we recently found that pretreatment with systemic prednisone (20 mg three times a day for 48 hours) had no effect during the early reaction on either the symptoms reported or the levels of histamine, prostaglandin D₂, tosyl-L-arginine methyl ester (TAME)-esterase activity, or albumin recovered in nasal secretions.⁵ During the late….