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Histamine H 4 receptor antagonism reduces hapten‐induced scratching behaviour but not inflammation
Author(s) -
Roßbach Kristine,
Wendorff Stephanie,
Sander Kerstin,
Stark Holger,
Gutzmer Ralf,
Werfel Thomas,
Kietzmann Manfred,
Bäumer Wolfgang
Publication year - 2009
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2008.00762.x
Subject(s) - scratching , antagonism , receptor antagonist , allergic contact dermatitis , pharmacology , histamine , hapten , allergic inflammation , antagonist , medicine , inflammation , chemistry , allergy , immunology , allergen , receptor , antigen , physics , acoustics
Effects of the histamine H 4 receptor antagonist JNJ 7777120 (1‐[(5‐chloro‐1 H ‐indol‐2‐yl)carbonyl]‐4‐methylpiperazine) were tested in two models of allergic contact dermatitis. Dermatitis was induced by 2,4‐dinitrochlorobenzene and toluene‐2,4‐diisocyanate, which differ in their Th1–Th2 profile in that way that 2,4‐dinitrochlorobenzene is a classical contact allergen with a pronounced Th1‐mediated inflammation, while the respiratory chemical allergen toluene‐2,4‐diisocyanate induces a Th2‐dominated inflammation. JNJ 7777120 (15 mg/kg) administered 2 h and 30 min before and 1 h after challenge did not reduce the hapten‐induced ear swelling determined 24 h after challenge. This was confirmed by histological evaluation of the ear skin. A repeated administration of the haptens to the rostral part of the back of sensitized animals resulted in a frequent scratching behaviour. An administration of JNJ 7777120 (15 mg/kg) 30 min before challenge reduced this hapten‐induced scratching significantly. The H 1 receptor antagonist cetirizine also reduced the scratching bouts in sensitized mice. A combination of H 1 and H 4 receptor antagonists resulted in the strongest inhibition of scratching behaviour associated with allergic dermatitis. These results indicate that H 4 receptor antagonism fails to reduce the allergic inflammatory response but strongly inhibits allergen‐induced itch. Thus, a combination of H 4 and H 1 receptor antagonism might be a new strategy to treat pruritus related to allergic diseases like atopic dermatitis.