Mast Cells in Atopic Diseases: More Than Just Histamine

Abstract

Mast cells are present in all tissues and are able to release multiple mediators in response to allergic, autoimmune, environmental, neurohormonal and pathogenic triggers. Histamine has received most of the attention in terms of pathophysiology and drug development, while tryptase remains to this date with no clear function and no known inhibitor. Mast cells can also release pro-inflammatory and pruritogenic molecules, such as IL-6 and IL-31, selectively without degranulation. One such critical molecule is platelet activating factor (PAF), which is vasoactive, can cause wheal and flare on ita own, but can also stimulate eosinophils and mast cells that are critical in the pathogenesis of chronic spontaneous urticaria (CSU) and rhinitis. Mast cell-derived cytokines and PAF have also been implicated in inflammatory processes including COVID-19. Among the second generation histamine-1 receptor antagonists, rupatadine is more effective overall, it has potent anti-PAF activity, and also inhibits activation of human mast cells and eosinophils. Rupatadine could, therefore, serve as a first-line drug for CSU and rhinitis, but may also be used, especially for patients resistant to antihistamines.