Allergic rhinitis: not purely a histamine-related disease

Allergic rhinitis is an inflammatory disorder of the nasal mucosa typified by the symptoms of nasal itch, sneeze, anterior nasal secretions, and nasal blockage. These symptoms arise from the interaction between mediators and neural, vascular, and glandular structures within the nose. Nasal itch, sne ezes, and rhinorrhoea are predominantly neural in origin, while nasal obstr uction is predominantly vascular. Nasal biopsy studies show accumulation of eosinophils within the lamina propria and epithelium and an increase in ti ssue and cell surface basophils in both seasonal and perennial allergic rhi nitis. These cells are in an activated state. Within the epithelium, increa sed numbers of mast cells, T cells and Langerhans' cells, which induce T-ce ll activation, are found. The accumulation of these cells can be linked to chemokine and cytokine generation by the epithelial cells themselves. Thus, the tissue cell. recruitment is orchestrated by activated mast cells, T ce lls, and epithelial cells, with the recruited tissue eosinophils also contr ibuting to their persistence at this site through autocrine mechanisms. Mas t cells generate an array of mediators including histamine, tryptase, leuko trienes, and prostaglandins. Histamine is also generated by basophils. Eosi nophils and basophils contribute to the leukotriene synthesis within the ti ssue. Histamine nasal insufflation induces nasal itch, sneeze, and rhinorrh oea as well as nasal blockage, thereby reproducing all the symptoms of alle rgic rhinitis. These effects are primarily mediated by H-1-receptors, and H -1-receptor antagonists are a prominent treatment. Antagonism of histamine at these receptors reduces symptoms by about 40-50%, with the greatest effe ct on the neurally mediated responses. Thus, histamine is a major mediator of allergic rhinitis, but not the sole contributor. Nasal insufflation with leukotrienes, prostaglandins, or kinins is associated with the development of nasal blockage. These mediators act primarily on the nasal vasculature and, in this respect, leukotrienes are potent mediators. Leukotrienes also induce plasma protein exudation, which contributes to the anterior nasal se cretions. Studies with combination products have suggested that modifying t he effects of both leukotrienes and histamine has complementary effects in relieving nasal symptoms, indicating that both these mediators are relevant to disease expression.