507 Skin inflammation leads immunoglobulin G aggregation and deposition in multiple organs

Abstract

and 4 Sanofi-Genzyme, Framingham, MA Topically applied Imiquimod has been shown to induce psoriasis-like skin inflammation in mice. The use of larger animals such as rats would enable the use of clinical research techniques. We therefore characterized the psoriasis-like inflammation in the Imiquimod rat model using the technique of dermal Open Flow Microperfusion (dOFM) for sampling of biomarkers in inflamed and healthy skin. Psoriasis-like skin inflammation was induced on a skin test site of Sprague-Dawley rats by applying a daily dose of topical Imiquimod. Half of the animals additionally received a daily dose of oral dexamethasone to prevent the Imiquimod-induced skin inflammation. Skinfold thickness, erythema and scaling of this skin were assessed daily. After 8 days, dermal interstitial fluid was sampled from Imiquimodtreated skin and from untreated skin with dOFM in both groups. The samples were analyzed for forty cytokines and mediators. Topical Imiquimod induced psoriasis-like local skin inflammation in those animals not receiving oral dexamethasone. Skinfold thickness and the scores for erythema and scaling increased significantly over 8 days. The key cytokine for psoriasis inflammation, IL-17A, was only detected in dOFM samples from Imiquimod-treated inflamed skin. The concentrations of several other mediators were significantly different between treated and untreated skin, and different to those in animals that received oral dexamethasone. This study demonstrates the utility of the Imiquimod model in rats for the preclinical testing of novel anti-psoriatic drugs. Moreover, the study demonstrates that dOFM is a valuable tool in preclinical and clinical drug development.