Use of a Canine Model of Atopic Dermatitis to Investigate the Efficacy of a CCR4 Antagonist in Allergen-Induced Skin Inflammation in a Randomized Study

作者：Murray Clare; Ahrens Kim; Devalaraja Matt; Dymond Mike; Fagura Malbinder; Hargreaves Adam; Holt Alison; Peers Ian; Price Sally; Reens Jaimini; Riley Rob; Marsella Rosanna^*

来源：Journal of Investigative Dermatology, 2016, 136(3): 665-671.

DOI：10.1016/j.jid.2015.11.001

Atopic dermatitis (AD) is an inflammatory skin disease characterized by infiltration of skin homing lymphocytes into the dermis. Most of these lymphocytes express the chemokine receptor CCR4, and the frequency of blood CCR4(+) lymphocytes correlates with AD disease severity. Canine AD is a pruritic inflammatory condition that shows many features of the human disease, including CCR4 overexpression. Therefore, we tested a potent selective CCR4 antagonist in an allergen challenge model of canine AD, both clinically and histologically, to investigate whether this chemokine pathway plays a role in the inflammatory response. Using a four-period randomized cross-over study design, 14 beagles were challenged with allergen and clinically monitored. Biopsy samples were taken before and after allergen challenge. A clear reduction of clinical scores was observed with oral prednisolone (P < 0.0001) but not for the CCR4 inhibitor. A subset of the dogs (5/13) showed partial inhibition (30-49%) of the clinical signs with CCR4 inhibitor treatment, and this finding was supported by the results of histopathologic analysis of skin biopsy samples. This partial response is consistent with redundancy in chemokine pathways and highlights the need for therapies blocking multiple pathways. This study shows the utility of this canine model of AD for testing new therapeutic agents.

• 出版日期2016-3