Effect of Histamine H4 receptor on allergic diseases

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Background : The present study observed effects of the histamine H4 receptor on chronic allergic contact dermatitis induced by repeated challenge in mice.Methods : Acute contact dermatitis was induced by single epicutaneous challenge of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the ear. Chronic allergic contact dermatitis was developed by repeated epicutaneous challenge using TNCB on the dorsal back skin. H4 receptor antagonist JNJ7777120 was administered to wild-type mice, while H4 receptor agonist 4-methylhistamine was administered to histidine decarboxylase (HDC) (-/-) mice that synthesized no histamine.Results : HDC (-/-) mice did not differ phenotypically from HDC (+/+) mice and H4 receptor antagonist/agonist did not have clinical effects in terms of acute contact dermatitis reactions. H4 receptor antagonist ameliorated skin eczematous lesions induced by repeated TNCB challenge in HDC (+/+) mice. On the contrary, H4 receptor agonist exacerbated skin lesions exclusively in HDC (-/-) mice. Application of H4 receptor agonist induced migration of mast cells and eosinophils in skin lesions and H4 receptor antagonist suppressed these changes. H4 receptor was immunohistochemically detected on mast cells in eczematous lesions. Levels of interleukin (IL)-4, -5, and -6 in lesions were decreased, whereas levels of interferon-γ and IL-12 were increased by H4 receptor antagonistic activity. Serum Immunoglogulin E levels rapidly increased with repeated challenge, but decreased with H4 receptor antagonist.Conclusion : Since chronic allergic contact dermatitis is developed by H4 receptor stimulation, H4 receptor antagonists might represent new candidate drugs for treating chronic allergic contact dermatitis.