Topical Application of Fluoxetine Improves <scp>DNCB</scp>‐Induced Atopic Dermatitis in Mice

This study aimed to assess the therapeutic effects and underlying mechanisms of topical fluoxetine application in an atopic dermatitis (AD)-like mouse model. An AD-like mouse model was established using 2,4-dinitrochlorobenzene (DNCB) and treated with topical applications of fluoxetine on skin lesions. The therapeutic efficacy was evaluated by measuring the number of scratches, skin thickness, trans-epidermal water loss (TEWL), and skin moisture levels. Histopathological changes were examined through haematoxylin and eosin staining and toluidine blue staining to assess the local inflammatory state. Quantitative PCR (qPCR) was used to measure the expression of Th2-related cytokines (IL-5, IL-13, and IL-31) in skin lesions. Serum levels of IgE and thymus- and activation-regulated chemokine (TARC) were measured by enzyme-linked immunosorbent assay (ELISA). Topical fluoxetine significantly alleviated lesion symptoms in AD-like mice, reducing skin thickness and the number of scratching incidents. The treatment enhanced skin barrier recovery and reduced the infiltration of inflammatory cells, especially mast cells. Levels of Th2-related cytokines (IL-5, IL-13, and IL-31), indicative of local immune status, were also decreased. Serum concentrations of IgE and TARC showed a downward trend, with a more pronounced decrease in TARC levels. Our findings support the therapeutic role of topical fluoxetine in an AD-like mouse model through the repair of the skin barrier and inhibition of the Th2 inflammatory response in skin lesions, while also alleviating pruritus. These results suggest that fluoxetine may be a potential therapeutic candidate for AD.