Allergic rhinitis: Pathophysiology

The inflammatory response in the nasal mucosa in subjects with allergic rhinitis challenged intranasally with an allergen includes an immediate IgE-mediated mast cell response as well as a late-phase response characterized by recruitment of eosinophils, basophils, and T cells expressing Th2 cytokines including IL-4, a switch factor for IgE synthesis, and IL-5, an eosinophil growth factor. Recent advances have suggested that additional pathways may contribute to the pathophysiology of allergic rhinitis including local synthesis of IgE in the nasal mucosa, the epithelial expression of cytokines that regulate Th2 cytokine responses (i.e., thymic stromal lymphopoietin, IL-25, and IL-33), and the activation of histamine receptors other than H₁ and H₂ such as H₄-histamine receptors. This review focuses on briefly reviewing well-established pathways in the pathophysiology of allergic rhinitis and then updating knowledge on recent advances in the pathophysiology of allergic rhinitis. The review references information obtained from original articles published and available online on PubMed. In vitro and in vivo studies indicate that B cells in nasal mucosa can be induced to express IgE. Preclinical studies show an important role for epithelial-derived cytokines (thymic stromal lymphopoietin, IL-25, and IL-33) in regulating Th2 responses at mucosal surfaces, and for H₄-histamine receptors in mediating itching. In addition, regulatory T cells may play an important role in mediating active tolerance to allergens. An improved understanding of the pathophysiology of allergic rhinitis may provide important insight into novel therapeutic targets.