Immunopharmacology of Nasal Allergic Reactions

Abstract

The technique of nasal provocation followed by lavage was used to study the pharmacology and pathophysiology of upper airway allergic reactions. The levels of histamine, TAME-esterase activity, kinins, and arachidonic acid metabolites were measured in the recovered nasal lavage fluid obtained during the early and, in certain cases, the late phase and rechallenge reactions to antigen. Leukocytes contained in the lavage were counted and differentiated. Topical application of azatadine and systemic administration of theophylline reduced both mediators and symptoms during the early reaction, probably by inhibiting antigen-induced mast cell activation. Pretreatment with aspirin decreased the concentration of cyclooxygenase products during the early reaction without ameliorating symptoms. Administration of systemic steroids ablated the increase of mediators and symptoms and the mucosal accumulation of eosinophils and mononuclear cells, but not of neutrophils during the late phase reaction, without affecting the mediators or symptoms of the early reaction, with the exception of kinins. Topical steroids reduced both the amount of mediators and the severity of symptoms during the early, late, and rechallenge reactions. The accumulation of eosinophils, basophils, neutrophils, and mononuclear cells during the late phase reaction was also significantly reduced. Thus, this nasal challenge model has helped us to gain insights into the pathophysiology of allergic reactions and the pharmacology of their treatment and can be used to examine the efficacy of pharmacologic agents designed for the treatment of such reactions.