B 1 and B 2 kinin receptor blockade improves psoriasis-like disease

The entire kallikrein-kinin system is present in the skin, and it is thought to exert a relevant role in cutaneous diseases, including psoriasis. The present study was designed to evaluate the relevance of kinin receptors in the development and progression of a model of psoriasis in mice. The effects of kinin B and B receptor knockout and of kinin receptor antagonists (SSR240612C or FR173657) were assessed in a model of psoriasis induced by imiquimod in C57BL/6 mice. Severity of psoriasis was assessed by histological and immunohistochemical assays of skin, along with objective scores based on the clinical psoriasis area and severity index. Both kinin receptors were up-regulated following 6 days of imiquimod treatment. Kinin B and B receptor deficiency and the use of selective antagonists show morphological and histological improvement of the psoriasis hallmarks. This protective effect was associated with a decrease in undifferentiated and proliferating keratinocytes, decreased cellularity (neutrophils, macrophages, and CD4 T lymphocytes), reduced γδ T cells, and lower accumulation of IL-17. The lack of B receptors resulted in reduced CD8 T cells in the psoriatic skin. Relevantly, blocking kinin receptors reflected the improvement of psoriasis disease in the well-being behaviour of the mice. Kinins exerted critical roles in imiquimod-induced psoriasis. Both B and B kinin receptors exacerbated the disease, influencing keratinocyte proliferation and immunopathology. Antagonists of one or even both kinin receptors might constitute a new strategy for the clinical treatment of psoriasis.