Blockade of Interleukin-33 Attenuates Allergic Contact Dermatitis in Model Mice: Possible Mechanism via Eosinophil Infiltration

Abstract

Background: Interleukin (IL)-33, a novel member of the IL-1 family, is mainly produced by epithelial cells and endothelial cells. Effects of IL-33 on allergic diseases have been reported. Allergic contact dermatitis is a clinical form of contact hypersensitivity that involves a delayed-type hypersensitivity reaction. We previously reported that IL-33 is induced by tumor necrosis factor-alpha and interferon-gamma in keratinocytes and plays a critical role in allergic contact dermatitis. However, the mechanism underlying how IL-33 is involved in the pathogenesis of allergic contact dermatitis is not fully understood. We investigated the role of IL-33 in allergic contact dermatitis using model mice. Methods: Allergic contact dermatitis model mice were generated. Epidermal thickness and eosinophil infiltration in the dermis were evaluated by histology. The function of IL-33 was investigated by in vivo administration of an anti-IL-33 antibody. Results: Epidermal thickness was increased in the ear lesions of allergic contact dermatitis model mice. We showed that eosinophil infiltration in the dermis was increased in the ear lesions. We further found that blockade of IL- 33 attenuated not only the epidermal thickness but also the eosinophil infiltration in the dermis in the ear lesions. Conclusions: IL-33 may promote inflammation via eosinophil infiltration in allergic contact dermatitis. Blockade of IL-33 may represent a novel and potent therapeutic strategy for allergic contact dermatitis.