Symptoms and aspects on eosinophil activity in allergic rhinitis

University dissertation from Department of Otorhinolaryngology, Lund University

Abstract: Allergic rhinitis is a major atopic disease. Even if much is known about the pathophysiology of this condition, and despite the fact that good treatments are available, there is a need for new treatment options, particularly for such aiming at new targets and reduced side effects. Recruitment and activation of eosinophils is a key feature of allergic rhinitis. Eosinophils have different activation modes with subsequent mediator release. Before and during a natural birch pollen season we take nasal biopsies and utilize electron microscopy to assess eosinophil activity. We show that allergen exposure produces a marked increase in piecemeal degranulation and release of mediators (indicated by ECP). Variations in onset, intensity, and duration of natural pollen exposure make it difficult to compare treatments in allergic rhinitis. To overcome this, we demonstrate that repeated individualized allergen challenges can produce symptoms and signs that mimic seasonal disease. We indicate the usefulness of the model by demonstrating dose-dependent symptom-reducing effects of a topical corticosteroid. Preceding observations suggest that ß2-agonists may be treatment candidates for allergic inflammation. Utilizing the above-mentioned allergen challenge model, we examine whether or not a topical ß2-agonist (formoterol) affect eosinophilic inflammation in allergic rhinitis. We demonstrate that the ß2-agonist neither affects symptoms and eosinophilic inflammation in allergic rhinitis nor the efficacy of a topical corticosteroid. Employing the allergen challenge model, and a topical corticosteroid as experimental tool, we demonstrate that production of the eosinophil chemokine CCL5 is particularly corticosteroid sensitive, suggesting that it may be a valid treatment target.