Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation

Abstract

Effects of the histamine H4 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 2h and 30 min before and 1h after challenge did not reduce the hapten-induced ear swelling determined 24h 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) 30min before challenge reduced this hapten-induced scratching significantly. The H1 receptor antagonist cetirizine also reduced the scratching bouts in sensitized mice. A combination of H1 and H4 receptor antagonists resulted in the strongest inhibition of scratching behaviour associated with allergic dermatitis. These results indicate that H4 receptor antagonism fails to reduce the allergic inflammatory response but strongly inhibits allergen-induced itch. Thus, a combination of H4 and H1 receptor antagonism might be a new strategy to treat pruritus related to allergic diseases like atopic dermatitis. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.