H2-antagonist in IgE-mediated type I hypersensitivity reactions: what literature says so far?

摘要

According to EAACI guidelines for diagnosis and treatment of anaphylactic reactions [1], H2 anti-histamines are recommended as third-line therapy in adjunct to H1-antagonists. A recent systematic review evaluating acute and long-term management options for anaphylaxis concluded that this combination may require additional research prior to being included in recommended guidelines [2]. Histamine is a well-known immunomodulatory molecule that is able to influence the Th1/Th2 balance through a number of mechanisms and receptors [3, 4]. Among CD4+ T lymphocytes, Th1 cells are known to express higher levels of H1-receptor in contrast to Th2 cells that express a significantly greater proportion of H2-receptors. Through the binding of H1-receptor, histamine is able to activate a Th1-characterized response by increasing the release of interferon­γ. Alternatively, through H2-receptor, histamine is able to suppress a Th1 and/or Th2 response [5] by inhibition of IL-2, IL-4, IL-13, and interferon­γ production [6]. Within dendritic cells, histamine can drive an increase in expression of both MCH-II and the co-stimulatory molecules CD80 and CD86. Binding at the H2 receptor on both dendritic cells and monocytes, it can induce the production of IL-10, and, specific to monocytes, downregulate the release of IL-12, thus shifting the Th1/Th2 balance toward Th2-dominance [7]. Within eosinophilic granulocytes, histamine presents contrasting effects: low concentrations induce an increase in chemotaxis through H4-receptors, whereas greater concentrations are responsible for decreased chemotaxis via H2-receptors [6].