Revisiting Cyclosporine in the Age of Biologics: Update on Efficacy and Mechanism of Action

psoriasis and the ability to treat this disease with immunosuppressants has greatly expanded in the past few decades. With respect to the pathogenesis of psoriasis, the entire refocusing from keratinocyte hyperproliferation to immunology started with the serendipitous discovery that immune modulating agents, namely cyclosporine, led to undeniable and often dramatic psoriasis improvement with no effect on keratinocyte reproduction. Eventually, understanding the role of immunology in psoriasis combined with new knowledge of protein engineering techniques has given us the capability to manufacture specific proteins that selectively alter the immunological processes in psoriasis, leading to the advent of biologics. However, of the immunosuppressive agents, cyclosporine remains one of the most efficacious agents available for the treatment of psoriasis. Cyclosporine was first extracted in 1969 from the fungus Tolyplocadium inflatum Gams and in 1976 Borel reported immunosuppressive properties of cyclosporine in animal models. Three years later, cyclosporine A was used experimentally in transplant patients to prevent graft rejection, and it was in these trials that Muller reported improvement of lesions in transplant patients who happened to have psoriasis. Following this discovery, further research led to a preliminary understanding of the mechanism of action of cyclosporine. Cyclosporine permeates into target cells and binds to molecules known as the cyclophilins. This Revisiting Cyclosporine in the Age of Biologics: Update on Efficacy and Mechanism of Action