Histamine in asthmatic and fibrotic lung disorders

Abstract

Histamine has long been known to mediate inflammatory and allergic responses acting predominately through H1 receptors and H1 receptor antagonists have been used to treat allergic rhinitis for many years. Since its discovery, histamine H4 receptor has been identified as a potential drug target for the treatment of allergic and inflammatory lung disease and has been identified as a potential modulator of allergy and inflammation in animal models. The use of the H4 receptor (H4R) antagonist JNJ7777120 in mouse and guinea pig models of allergic bronchoconstriction highlighted the involvement of this receptor in asthma. Histamine released from tissue mast cells by the cross-linking of antigen with IgE is deaminated by amine oxidases, enzymes widely distributed among living organisms and a histaminase, purified from the pea seedlings has been shown to exert a protective effect in an experimentally animal model of asthmalike reaction in guinea pig. In an animal model of fibrosis, H4R antagonists demonstrated anti-inflammatory and anti-fbrotic properties, suggesting a possible therapeutic potential in the treatment of Th2-mediated diseases, including pulmonary fibrosis.