Food allergy, anaphylaxis, dermatology, and drug allergyHistamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus
Section snippets
Animals
All experiments and procedures were performed according to on-site Institutional Animal Care and Use Committee standards and regulations. Female CD-1 mice (Charles River, Hollister, Calif) approximately 10 to 12 weeks old, H4R knockout (−/−) and littermate, wild-type (+/+) mice (c57bl/6 sv129),23 or mast cell-deficient (WBBF1-W/Wv) and sufficient control (WBB6F1-+/+) mice 10 to 12 weeks of age (Jackson Laboratories, Bar Harbor, Maine) were used. H4R−/−/+/+ bone marrow chimera mice were produced
Histamine-mediated pruritus
Pruritic responses to histamine were examined in H4R−/− mice in comparison with wild-type controls. Histamine injected intradermally induced a pruritic response in a dose-dependent fashion in H4R+/+ mice, whereas H4R−/− mice showed a significantly reduced (P < .001 vs +/+) response at all doses (Fig 1, A). To confirm the role of the H4R in this response, intradermal injection of histamine also induced itch in a dose-dependent fashion in CD-1 mice (data not shown), with a dose of 300 nmol used
Discussion
The ability of histamine to produce pruritic responses in humans is incontrovertible. However, its involvement in various chronic pruritic diseases has been debated, largely because of the ineffectiveness of existing H1R and H2R antagonists in the clinic. Here we demonstrate the definitive role of the histamine H4 receptor in murine itch and investigate the possible mechanisms involved in H4R-mediated pruritus using clinically relevant pruritogens and allergic mechanisms.
The pruritic response
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Disclosure of potential conflict of interest: P. J. Dunford, K. N. Williams, P. J. Desai, L. Karlsson, and R. L. Thurmond are employed by Johnson & Johnson Pharmaceutical Research & Development, LLC. D. McQueen has declared that he has no conflict of interest.