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.

Clinical impact in the real life of guidelines recommendations for atopic dermatitis in a tropical population (TECCEMA cohort)

“…This observation also suggests that pruritus plays a major role in the patient's perception of control even more that eczema severity or the size of area affected. Some controlled studies have shown that antihistamines, have a poor effect in pruritus from patients with dermatitis, 21 however, other studies indicate that may could help skin repair. 22 The possible beneficial effects of antihistamines must be weighed against the known adverse effects such as sedation.…”

Antihistamines in Atopic Dermatitis Therapy

“…They supposed that the next generation antihistaminic agents possessing H1R and H4R antagonistic actions would be a potent therapeutic drug for AD [45] …”

Histamine H4 Receptor in Allergic Dermatitis

“…Furthermore, the number of eosinophils and mast cells are also decreased by combined therapy compared with olopatadine monotherapy [47] . The combined administration of HH4R and HH1R antagonists inhibits the itch response and chronic allergic inflammation, and has a pharmacological effect similar to that of prednisolone [35] .…”

“…Histamine plays roles in the induction of allergic inflammation by activating basophils via HH4R [35] . Basophils express HH4R mRNA levels.…”