The histamine H4 receptor: Targeting inflammatory disorders

Abstract

The discovery of the histamine H4 receptor has added a new chapter to the century of extensive biogenic amine research. The human histamine H4 receptor is mainly expressed in cells of the human immune system (e.g. mast cells, eosinophils, monocytes, dendritic cells, T cells) and mediates several effects on chemotaxis with numerous cell types. The distinct expression pattern and the immunomodulatory role highlight its physiological relevance in inflammatory and immunological processes. Inflammatory conditions, e.g. allergy, asthma and autoimmune diseases, were for a long time thought to be mainly mediated by activation of the histamine H1 receptor subtype. However, in the treatment of diseases as chronic pruritus, asthma and allergic rhinitis the use of histamine H1 receptor antagonists is unsatisfying. Selective H4 receptor ligands and/or synergism of histamine H1 and H4 receptor modulation may be more effective in such pathophysiological conditions. Promising preclinical studies underline its role as an attractive target in the treatment of inflammatory and autoimmune disorders. Meanwhile, first histamine H4 receptor antagonist has reached clinical phases for the treatment of respiratory diseases.