P047 : Development of psoriasis animal model using interleukin-10 knockout mice

Background: Psoriasis had been suggested as a skin disease resulting from epidermal hyperplasia, but it is now regarded as a systemic inflammatory disease induced by Th1 and Th17 cells, sharing common pathophysiology with various autoimmune diseases. A previous study showed that imiquimod-induced psoriasis-like skin inflammation in mice resembles human psoriasis. However, psoriasis animal model reflecting chronic inflammatory course is not yet established. Objectives: This study was aimed to develop an animal model reflecting chronic relapsing course of psoriasis. Methods: We performed a comparative study of the different inflammatory reaction induced by imiquimod in interleukin (IL)-10 knockout and wild type mice. Results: IL-10-/- mice showed more rapid induction of psoriasis-like inflammation and higher severity index than IL-10+/+ did during the 12-day of imiquimod application. Whereas inflammation was attenuated in IL-10+/+ on day 12, inflammation in IL-10-/- was gradually increased. Histopathologically, IL-10-/- showed more inflammatory cell infiltration. Quantitative RT-PCR revealed significantly higher imiquimod-induced IL-23 in IL-10-/- mice. IL-10-/- also showed significantly higher protein level expression of imiquimod-induced IL-17A, interferon- ャ, tumor necrosis factor-メ and IL-12p70 in ELISA. Conclusion: IL-10-/- mice model with imiquimod application may reflect the chronic course of psoriasis. Moreover, it may be a model of severe and early onset psoriasis.