Effect of histamine H4 receptor antagonist on allergic rhinitis in mice

The aim of this study was to clarify the effect of histamine H-4 receptor antagonist, JNJ7777120 (1-[(5-Chloro-1H-indol-2-yl)carbonyl]-4-methyl-piperazine) on allergic rhinitis in mice. We measured allergic symptoms (sneezing and nasal rubbing), serum total IgE and the levels of cytokines in nasal lavage fluid. Histamine H-4 receptor antagonist, JNJ7777120, caused the dose-dependent inhibition of nasal symptoms by single and repeated intranasal administrations: however, JNJ7777120 caused no inhibition of serum total IgE by single and repeated intranasal administrations. Therefore, we investigated the effect of JNJ7777120 by oral administration. JNJ7777120 also caused a significant inhibition of nasal symptoms by both single and repeated oral administrations. In addition, repeated oral administration of JNJ7777120 caused significant inhibition of serum total IgE. Furthermore,JNJ7777120 caused a significant decrease in the levels of IL-4 and a significant increase in the levels of IFN-gamma in nasal lavage fluid. These results indicated that histamine H-4 receptor is closely related with allergic rhinitis and is important in the pathogenesis of allergic rhinitis. From these results, it can be concluded that histamine H-4 receptor antagonist might be a new strategy to treat allergic rhinitis with immunomodulatory function. (C) 2009 Elsevier B.V. All rights reserved.