Chapter 5 Histamine in Asthmatic and Fibrotic Lung Disorders

Abstract

Histamine has long been known to mediate inflammatory and allergic responses acting predominately through H 1 receptors and H 1 receptor antagonists have been used to treat allergic rhinitis for many years. Since its discovery, histamine H 4 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 H 4 receptor (H 4 R) 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, H 4 R antagonists demonstrated anti-inflammatory and anti-fibrotic properties, suggesting a possible therapeutic potential in the treatment of Th2-mediated diseases, including pulmonary fibrosis.