Thalidomide Improves Psoriasis-like Lesions and Inhibits Cutaneous VEGF Expression without Alteration of Microvessel Density in Imiquimod- induced Psoriatic Mouse Model

BACKGROUND:Psoriasis is a chronic inflammatory skin disorder of unknown etiology. Increasing evidence suggests that psoriasis is probably an angiogenesis-dependent disease. Thalidomide has been reported being able to inhibit the effects of fibroblast growth factor 2 and vascular endothelial growth factor (VEGF), and inhibit tumour necrosis factor-alpha synthesis, and suppress tumour necrosis factor-induced nuclear factor-kappa B activation in Jurkat cells, resulting in suppression of proliferation inflammation, angiogenesis, and the immune system, which are related to the pathogenesis of psoriasis. OBJECTIVE:Our study evaluated the influence of thalidomide on the lesional alterations, VEGF expressions and angiogenesis in imiquimod-induced mouse model. METHODS:Balb/c female mice (n=48) 8-12 weeks of age were randomly divided into 6 groups including negative control (vaseline cream), positive control (5% imiquimod cream), and experimental groups including low-dose (10 mg/kg.d), moderate-dose (30 mg/kg.d) and high-dose thalidomide (85 mg/kg.d), and acitretin group (6 mg/kg.d). Serum levels of VEGF-A were quantified by enzyme-linked immunosorbent assay. VEGF protein expression was measured by western blotting and the microvessel density by immunohistochemical staining. RESULTS:The total psoriasis area and severity index scores in the moderate- and high-dose thalidomide and acitretin groups decreased significantly (p 0.05 for both). There were no differences for serum VEGF-A levels and the density of microvessels among the positive and experimental groups. CONCLUSION:Thalidomide can improve the psoriasis-like lesions and inhibit the expression of cutaneous VEGF in imiquimod-induced psoriatic model with dose-dependence, however, it does not alter circulating VEGF-A levels and microvessel density in dermis.