Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation.
Exp Dermatol
; 18(1): 57-63, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-18647342
ABSTRACT
Effects of the histamine H(4) receptor antagonist JNJ 7777120 (1-[(5-chloro-1H-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
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Prurido
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Células Th2
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Receptores Acoplados a Proteínas G
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Haptenos
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Antagonistas dos Receptores Histamínicos H1
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Indóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Exp Dermatol
Assunto da revista:
DERMATOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Alemanha