Are the anti-allergic properties of H1-antihistamines of any clinical relevance?

Summary Histamine is an ubiquitous messenger molecule synthetized and released from human basophils, mast cells and neurons. Its various biological effects are mediated by three pharmacologically defined receptors termed the H1, H2 and H3-receptors. The H1-receptor was the first member of this family to be pharmacologically defined with the advent of selective antagonists, the « antihistamines , which are widely used to treat allergic disorders. Recent evidence indicates that certain antihistamines exert antiallergic effects not related to H1-antagonism. However, these effects require higher doses than those regularly used. We have demonstrated that histamine induces a concentration-dependent release of IL-6, TNF-α and β-glucuronidase from human lung macrophages. These effects are inhibited by fexofenadine, an H1-receptor antagonist, but not by cimetidine, an H2-receptor antagonist. The finding that fexofenadine inhibits the human lung macrophages-activating property of histamine raises the possibility that long-term treatment with fexofenadine might inhibit tissue damage caused by human lung macrophages activated by histamine immunologically released by basophils and mast cells.