Original Article
The Histamine H4 Receptor Mediates Inflammation and Pruritus in Th2-Dependent Dermal Inflammation

https://doi.org/10.1038/jid.2009.358Get rights and content
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The role of histamine H4 receptor (H4R) was investigated in a T-helper type 2 (Th2)-cell-mediated mouse skin inflammation model that mimics several of the features of atopic dermatitis. Treatment with two specific H4R antagonists before challenge with FITC led to a significant reduction in ear edema, inflammation, mast cell, and eosinophil infiltration. This was accompanied by a reduction in the levels of several cytokines and chemokines in the ear tissue. Upon ex vivo antigen stimulation of lymph nodes, H4R antagonism reduced lymphocyte proliferation and IL-4, IL-5, and IL-17 levels. One explanation for this finding is that lymph nodes from animals dosed with the H4R antagonist, JNJ 7777120, contained a lower number of FITC-positive dendritic cells. The effect of H4R antagonism on dendritic cell migration in vivo may be an indirect result of the reduction in tissue cytokines and chemokines or a direct effect on chemotaxis. In addition to anti-inflammatory effects, JNJ 7777120 also significantly inhibited the pruritus shown in the model. Therefore, the dual effects of H4R antagonists on pruritus and Th2-cell-mediated inflammation point to their therapeutic potential for the treatment of Th2-mediated skin disorders, including atopic dermatitis.

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These authors contributed equally to this work