Premium
The antagonism of histamine H 1 and H 4 receptors ameliorates chronic allergic dermatitis via anti‐pruritic and anti‐inflammatory effects in NC / N ga mice
Author(s) -
Ohsawa Y.,
Hirasawa N.
Publication year - 2012
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2012.02854.x
Subject(s) - histamine , medicine , atopic dermatitis , pharmacology , antagonist , histamine h4 receptor , immunology , receptor antagonist , chemokine , inflammation , receptor , histamine h2 receptor
Background Although histamine H 1 receptor ( H 1 R ) antagonists are commonly used to treat atopic dermatitis, the treatment is not always effective. The histamine H 4 receptor ( H 4 R ) was recently described as important to the pruritus in dermatitis. Here, we investigated whether the combination of a H 1 R antagonist plus a H 4 R antagonist attenuates chronic dermatitis in NC / N ga mice. Methods Chronic dermatitis was developed by repeated challenges with picryl chloride on the dorsal back and ear lobes. The therapeutic effects of the H 1 R antagonist olopatadine and H 4 R antagonist JNJ 7777120 on scratching and the severity of dermatitis were evaluated. In addition, the mechanisms responsible for the anti‐allergic effects of H 1 R and/or H 4 R antagonism were examined using bone marrow‐derived mast cells ( BMMC ) and keratinocytes. Results JNJ 7777120 attenuated scratching behavior after a single administration and improved dermatitis, as assessed with clinical scores, pathology, and cytokine levels in skin lesions when administered repeatedly. These effects were augmented by combined treatment with olopatadine, having a similar therapeutic efficacy to prednisolone. JNJ 7777120 inhibited dose‐dependently the production of thymus and activation‐regulated chemokine/ CCL 17 and macrophage‐derived chemokine/ CCL 22 from antigen‐stimulated BMMC . In addition, olopatadine reversed the histamine‐induced reduction of semaphorin 3 A m RNA in keratinocytes. Conclusion Combined treatment with H 1 R and H 4 R antagonists may have a significant therapeutic effect on chronic dermatitis through the synergistic inhibition of pruritus and skin inflammation.