Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease characterized by pruritus and eczematous skin lesions. It has been described that the repeated topical application of the hapten oxazolone to the ears of sensitized mice cause lesions that mimic some features of AD. However, in most of the published reports the number of challenges is significantly high (6 to 12), which translates into a long duration of the assay and causing a significant distress to the animals. In the present study we have characterized a model of dermatitis induced by 4 challenges of oxazolone applied on days 7, 9, 11 and 14 post-sensitization. Ear samples were obtained on day 15. Using this protocol, the main clinical signs consist of an increase in ear skin thickness and erythema. Histological analysis reveals the presence of a diffuse, moderate acanthosis with frequent areas of parakeratosis and pustules. A dermal infiltration of macrophages, lymphocytes and polymorphonuclear cells, as well as proliferation of fibroblasts is also observed. Skin biopsies show increased levels of mRNA expression of 11 cytokines, including the Th2 markers IL-4, IL-13, IL-22 and IL-31, and a reduction in the expression of loricrin, indicating barrier disruption. To further validate the model, we assessed the effect of commercial formulations of the anti-inflammatory drugs betamethasone, tacrolimus and crisaborole. The three topical treatments were able to reduce ear thickness, erythema and the expression of IL-4, IL-13 and IL-33, whilst increasing that of loricrin. Of note, betamethasone inhibited IL-22 expression whereas tacrolimus increased it and crisaborole had no effect at all. Overall, our results show that this model replicates several AD features and respond to approved topical drugs, making it suitable for screening purposes.

ESDR035 - Characterization of a murine model of dermatitis induced by oxazolone

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