Atopic dermatitis is one of the many diseases induced by environmental elements as an antigen and the incidences of AD have sharply increased recently
[5–9]. AD is a common chronic inflammatory skin disease, although fundamental etiology and therapy is still poorly understood
[6–9]. Treatment with steroid-based drugs has been used for treating AD, but has encountered some problems
It is well known that Dead Sea water has beneficial effects for treating skin diseases, including AD
. Recent studies reported that Dead Sea water has been used to treat psoriasis and atopic dry skin
. Dead Sea water is rich in some minerals compared to ocean water. Minerals, are essential nutrients for human, can trigger alterations on gene expression by initiating signaling events upstream of gene transactivation. Until the present, there are few studies for minerals and AD in human, however, the studies of mice reported that Staphylococcus aureus was increased on the skin of zinc-deficient mice before the development of AD-like eruptions, leading the authors to postulate that zinc may have an important role in the induction of dermatitis
. The deficiency of magnesium also induced AD-like skin lesions
. Because DSW also has enough minerals as well as Dead Sea water, in the present study, we demonstrate whether DSW also has an effect on amelioration of AD-like skin.
Before application of DSW to DNCB-elicited lesions, we screened the elemental composition of DSW and their concentrations (Table
1). There were some potential problems because DSW had high sodium concentration and salt-stress may induce inflammation
. Therefore, we examined CDSW, which was made by concentrating and desalinating DSW, and dilutions of CDSW were used. Although the concentration of the other elements in CDSW increased, the salt concentration was reduced (Table
1). Accordingly, we examined whether CDSW has an effect on AD induced by DNCB treatment in mice.
Although some symptoms of AD remained slightly, we have shown that repeated application of 10% CDSW improved the clinical severity score in DNCB-treated mice compared with a negative control. We scored five symptoms in skin lesions including itching, erythema, edema, excoriation/erosion and scaling/dryness to evaluate clinical skin severity. Among the treated animals, the 10% CDSW group had some edema, erosion and erythema, and did not differ dramatically from the 2% CDSW group. However, the itching was largely reduced by treatment with 10% CDSW. We also measured we measured TEWL and the moisture content in the epidermis and found that the 10% CDSW group had significantly improved skin barrier function and epidermis moisture. In addition, as demonstrated by histologic analysis, the 10% CDSW treatment reduced the infiltration of inflammatory cells, such as leukocytes and mast cells. These findings suggest that CDSW may restore skin barrier function.
Human AD disease is characterized by increased levels of Immunoglobulin E (IgE) in the blood
. IgE plays an important role in allergic responses and is especially associated with type-1 hypersensitivity. IgE is secreted from B cells by external antigens such as pollen and house dust mites
[10, 35]. Recent studies have reported that AD severity is related to an increase in total serum IgE levels
[36, 37]. Indeed, in our study, the clinical skin severity of DNCB-induced dermatitis was increased in accordance with up-regulation of total IgE levels in the serum. Mast cells are one class of inflammatory cells and the activation and degranulation of mast cells is tightly regulated by IgE. Total IgE affects mast cells and induces degranulation and triggers secretion of histamine and other inflammatory mediators
[10, 35, 38]. Among the released inflammatory mediators, histamine is one of the most potent mediators
. In AD skin lesions, mast cells infiltrate the dermis and elicit inflammation by releasing histamine and other mediators. Infiltration of inflammatory cells in the dermis, induced by DNCB, was inhibited by 10% CDSW (Figure
4) and significantly reduced total IgE and histamine levels in the serum. These results indicate that CDSW lowers serum histamine and IgE levels in DNCB induced murine AD model.
It was believed that inflammatory cytokines contribute to inflammation in skin lesions in AD
. T-helper cells (CD4+), a type of white blood cell, play an important role in the immune system and have two subfamilies with distinct regulatory and influencing functions, based on their cytokines: Th1 lymphocyte and Th2 lymphocyte
. Th1 lymphocytes produce IFN-γ and IL-2, while Th2 lymphocytes produce IL-4 and IL-10. Excessive release of these cytokines is an important part of inflammation in AD. Among these, it was reported that Th2 cytokines regulate IgE synthesis. Treatment of DNCB promoted Th2 cell responses, such as IL-4 and IL-10 production. Overexpressed IL-4 promotes the development of AD
. In our experiments, production of IL-4 and IL-10 was reduced by 10% CDSW treatment, which led to reduced serum IgE levels. Treatment with 10% CDSW did not have any significant effect on Th1 responses. Taken together, our data show that application of CDSW has a beneficial effect for treating AD-like symptoms.