Abstract

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder, and patients with AD suffer from severe psychological stress, which markedly increases the prevalence rate of depression and anxiety disorders in later life. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been reported to exert anti-inflammatory and immunosuppressive effects. However, it is unclear whether fluoxetine is effective in the treatment of AD through reducing psychological stress and inflammatory reaction. Here, we reported that a BALB/c mouse model of AD was induced by application of 2,4-dinitrochlorobenzene (DNCB) onto hairless dorsal skin. Chronic fluoxetine treatment (10 mg/kg per day, i.p.) significantly attenuated AD-like symptoms, as reflected by a dramatic decrease in scratching bouts, as well as a decrease in anxiety- and depressive-like behaviors. Furthermore, these behavioral changes were accompanied by a significant decrease in epidermal thickness, the number of mast cells in skin tissue, mRNA levels of interleukin-4 (IL-4) and IL-13 in the spleen, as well as serum immunoglobulin E (IgE) in the DNCB-treated mice by treatment with fluoxetine. Taken together, these results indicate that fluoxetine may suppress psychological stress and inflammatory response during AD development, and subsequently ameliorate AD symptoms, suggesting that fluoxetine may be a potential therapeutic agent against AD in clinic.

Highlights

  • Atopic dermatitis (AD), known as atopic eczema, is a common chronic inflammatory skin disease that is characterized by intense itching and recurrent eczematous lesions

  • It has been reported that repeated applications of 2,4-dinitrochlorobenzene (DNCB) to mouse skin induced AD-like skin lesions, which is associated with a significant increase in serum immunoglobulin E (IgE) and T-helper (Th) 2 cytokines such as interleukin-4 (IL-4) and IL-13 at the chronic dermatitis site (Kitagaki et al, 1995; Harada et al, 2005)

  • We confirm that repeated DNCB treatment induces the AD-like pathology, and demonstrate that chronic fluoxetine treatment reduces DNCB-induced inflammatory response and subsequently ameliorate AD symptoms in BALB/c mice

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Summary

Introduction

Atopic dermatitis (AD), known as atopic eczema, is a common chronic inflammatory skin disease that is characterized by intense itching and recurrent eczematous lesions. Most cases of AD currently are treated with emollients and topical anti-inflammatory agents such as topical corticosteroids and the topical calcineurin inhibitors. Many patients can be managed effectively, considerable number of patients still suffers from relapsing intolerable AD. These pharmacological therapies may cause various side effects including skin atrophy, telangiectases, purpura, and striae formation (Del Rosso and Friedlander, 2005). The use of less toxic alternative therapeutic agent against AD is imperative

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