Roles of histamine in the exacerbated allergic dermatitis

We established a novel dermatitis model in mice earlobes and analyzed the roles of histamine using specific antagonists for histamine receptors. After sensitization with picryl chloride (PiCl) by painting it on the earlobes of cyclophosphamide-treated mice, 12-O-tetradecanoylphorbol 13-acetate (TPA) was painted twice at the same site, and then allergic inflammation was induced by painting with PiCl. Histamine antagonists and cyclosporin A were administered i.v. The application of TPA shifted the PiCl-induced allergic inflammation from a delayed-type response to a biphasic response and increased the infiltration of eosinophils and mast cells at the inflammatory site. In this model, the PiCl-induced increase in the thickness of the earlobe in the immediate phase was suppressed by the histamine H1 antagonist pyrilamine. In contrast, the increase in the swelling in the late phase and the infiltration of eosinophils were suppressed by the H3/H4 antagonist thioperamide. The inhibitory effect of the combined treatment with pyrilamine and thioperamide on TPA-modified contact dermatitis was as potent as that of cyclosporin A. Histamine plays significant roles in early-phase swelling via H1 receptors and in late-phase swelling via H3/H4 receptors in this TPA-modified allergic dermatitis model.