title: The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical study.
abstract: Histamine plays important roles in inflammation and nervous irritability in allergic disorders, including atopic dermatitis (AD). It has been shown to regulate the expression of pruritic factors, such as nerve growth factor and semaphorin 3A, in skin keratinocytes via histamine H1 receptor (H1R). Furthermore, H1R antagonist reduced the level of IL-31, a cytokine involving the skin barrier and pruritus, in chronic dermatitis lesions in NC/Nga mice and patients with AD. Histamine plays roles in the induction of allergic inflammation by activating eosinophils, mast cells, basophils, and Th2 cells via histamine H4 receptor (H4R). H4R, in addition to H1R, is expressed on sensory neurons, and a decrease in scratching behaviors was observed in H4R-deficient mice and mice treated with a H4R antagonist. We found that the combined administration of H1R and H4R antagonists inhibited the itch response and chronic allergic inflammation, and had a pharmacological effect similar to that of prednisolone. Although the oral administration of H1R antagonists is widely used to treat AD, it is not very effective. In contrast, JNJ39758979, a novel H4R antagonist, had marked effects against pruritus in Japanese patients with AD in a phase II clinical trial. Next generation antihistaminic agents possessing H1R and H4R antagonistic actions may be a potent therapeutic drug for AD.
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohsawa
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism*; D000074040:Receptors, Histamine H4; D016896:Treatment Outcome
chemical_list: C418607:HRH4 protein, human; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D000074040:Receptors, Histamine H4