Imiquimod-applied Interleukin-10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state.

Abstract

Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison with previous models. IL-10 deficient and wild-type (WT) mice received either imiquimod or vehicle cream for 12days and were sacrificed on day 15. For earlier time point data, either imiquimod or vehicle cream was applied for 2days, and the mice were sacrificed on day 3. Imiquimod-applied IL-10 deficient mice showed more persistent psoriasis-like inflammation and higher severity index than did WT between day 8 and 15. Histopathologically, they demonstrated significantly thicker epidermis and larger number of CD45+, myeloperoxidase+ and IL-17+ cell counts on day 15. Quantitative reverse transcription-polymerase chain reaction with skin tissue revealed significantly higher imiquimod-induced IL-23p19 expression in imiquimod-applied IL-10 deficient mice on day 15. IL-10 deficient mice also showed significantly higher serum levels of imiquimod-induced IL-17A and tumor necrosis factor-α by enzyme-linked immunosorbent assay on day 15. Furthermore, IL-10 deficient mice showed more prominent increase of spleen weight and decrease of body weight in response to imiquimod application on day 3 and 15. In conclusion, IL-10 deficient mice model with imiquimod application may better reflect severe and persistent psoriasis with systemic inflammatory state.