Lack of preventing effect of systemically and topically administered histamine H1 or H4 receptor antagonists in a dog model of acute atopic dermatitis

Abstract

As there is evidence for an anti-inflammatory efficacy of histamine H(4) receptor (H4R) selective antagonists, we aimed at testing the efficacy of the H4R antagonists JNJ7777120 and JNJ28307474 in comparison with histamine H(1) receptor (H1R) antagonists hydroxyzine and cetirizine for skin lesion prevention in a canine model of acute atopic dermatitis. Six atopic Maltese-beagle dogs experimentally sensitized to Dermatophagoides farinae (Df) house dust mites were selected for this study. Twenty-four hours after challenge by epicutaneous application of Df, erythematous skin lesions were scored. In this blinded, placebo and active controlled study, topical JNJ7777120 or JNJ28307474 was applied as a 1% solution before allergen challenge. The latter was also given orally at 15 mg/kg before and after allergen challenge. A 0.015% triamcinolone acetonide solution was used as a positive control. The H1R antagonists hydroxyzine and cetirizine were administered orally before challenge in a second experiment. Twenty-four hours after challenge, placebo-treated animals had a median lesional score of 2. Treatment with topical and oral JNJ28307474 resulted in a median score of 2.5. After topical administration of JNJ7777120, the median lesional score was 2. Hydroxyzine and cetirizine did also not reduce the median score of the placebo treatment. Triamcinolone acetonide prevented all dogs from having any lesions. Determination of histamine in lesions revealed that only during the initiation increased concentrations of histamine were detected. In conclusion, the preventive administration of H1R or H4R antagonists has no impact on the development of acute skin lesions in this experimental canine atopic dermatitis model.