Combined treatment with H1 and H4 receptor antagonists reduces inflammation in a mouse model of atopic dermatitis

Publication date: August 2017
Source:Journal of Dermatological Science, Volume 87, Issue 2
Author(s): Hanna Köchling, Katrin Schaper, Jenny Wilzopolski, Ralf Gutzmer, Thomas Werfel, Wolfgang Bäumer, Manfred Kietzmann, Kristine Rossbach
BackgroundHistamine 4 receptor (H4R) antagonists are considered as new therapeutics for the treatment of atopic dermatitis (AD) and first clinical trials have already shown promising results. Histamine 1 receptor (H1R) antagonists are traditionally used to treat AD although the evidence for the efficacy is weak. The combined blockade of both, H1R and H4R, might provide synergistic anti-inflammatory.ObjectiveThe study was performed to test the anti-inflammatory potential of a combined treatment with an H1R and an H4R antagonist in a mouse AD model.MethodsThe development of ovalbumin-induced AD-like skin lesions was analysed mice treated with the H1R inverse agonist mepyramine, the H4R antagonist JNJ-39758979 or a combination of both.ResultsMice treated with mepyramine plus JNJ-39758979 showed less severe skin lesions, with a diminished influx of inflammatory cells, a reduced epidermal thickening and a lower level of IL-33 in lesional skin. Scratching behaviour was ameliorated in mice treated with the combination. Moreover, total numbers of skin-draining lymph node cells and splenocytes were significantly reduced. Both substances given alone did not elicit this strong anti-inflammatory effect.ConclusionH1R and H4R antagonists provide synergistic anti-inflammatory effects in a mouse model of AD. The combined therapy with H1R and H4R antagonists might represent a new strategy for the treatment of AD.



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