Material and methods: The atopic dermatitis-like skin lesions were induced by percutaneous challenge of 2,4,6-trinitro-1-chrolobenzene (TNCB) on the ear and back of NC/Nga mice. The KRG extract, evening primrose oil, cyclosporine and phosphate-buffed saline were administered orally by gastric tube. The effects of KRG and other drugs were assessed by measuring the clinical severity score, ear thickness, transepidermal water loss (TEWL), the number of scratching counts, total systemic IgE and IL-31 by ELISA, histologic changes of skin, and mRNA expression of TNF-α, IFN-γ, TSLP and IL-31. Each study group was divided into scratch-able and non-scratch-able subgroups to evaluate the impact of scratching behavior in atopic dermatitis.
Results: Oral administration of KRG significantly reduced clinical severity, ear thickness, and TEWL elevation. The number of scratching counts was also effectively lowered in KRG administered group compared to other treatment groups. The clinical results were also revealed in serologic and histologic changes. In the KRG group, the systemic IgE and IL-31 level was significantly lowered on the last day of the experiment. Histologically, epidermal hyperkeratosis, parakeratosis, and hyperplasia and dermal leukocytes and mast cell infiltration were suppressed by KRG. Immunochemistry of TNF-α, TSLP and IL-31 expression and quantitative RT-PCR showed that KRG effectively suppressed proinflammatory cytokines and Th2 response. Additionally, proactive restriction of scratching behavior by physical barrier reduced scratching counts and this improved clinical symptoms. Also, in non-scratch-able group there was lower inflammatory cell infiltration and lower TNF- α, TSLP, Il-31, and IFN-γ expression in the back tissue as well as lower systemic IL-31 level.
Conclusion: Therefore, we expect that the oral administration of KRG may control pruritus and skin inflammation by inhibiting the Th2 response. In addition, restriction of scratching behavior in early stage could be helpful in suppressing the itch-scratch vicious cycle and improving the clinical and systemic inflammations.