Inhibitory effect of topical Adelmidrol on antigen-induced skin wheal and mast cell behavior in a canine model of allergic dermatitis

A significant reduction in the antigen-induced wheal areas was observed on the 4th and 7th day of adelmidrol treatment. Moreover, cutaneous mast cell numbers were significantly decreased in biopsies obtained after 8 consecutive days of topical adelmidrol treatment.The results obtained in the present study show that topical treatment with adelmidrol might represent a new therapeutic tool in controlling the early and late allergic inflammatory skin responses in companion animals.Adelmidrol is the diethanolamide derivative of azelaic acid, i.e., naturally occurring dicarboxylic acid that has long proven to be an effective topical treatment for human inflammatory skin disorders [1], and whose mechanism of action has been extensively investigated [2]. Similar to the anti-inflammatory and anti-nociceptive compound palmitoylethanolamide (PEA) [3-12], adelmidrol belongs to the aliamide family [13,14], a group of fatty acid derivatives with cannabimimetic properties, able to control mast cell (MC) hyper-reactivity in several pathophysiological and pathological conditions [5,8,15-17]. We have recently found that PEA down-modulates the release of both preformed and newly-synthesized mediators from canine skin MCs challenged with immunologic stimuli [18]. Moreover, the PEA analogue adelmidrol has been shown to negatively control the behavior of canine skin MCs during pathophysiological conditions (i.e. healing of experimental wounds) [19]. In particular, a statistically significant increase of intracytoplasmic granular content of dermal MCs was shown in adelmidrol (2%)-treated wounds compared to control, thus suggesting the compound is effectively able to down-modulate skin MC degranulation in dogs [19]. Furthermore, the local application of adelmidrol confirmed the reduction in MC responses during chronic experimental inflammation, as shown by the significant decrease of mediators such as chymase which are selectively expressed by MCs and intimately involved in skin inflammati