Cytokine-based therapy in psoriasis

Abstract

Psoriasis and psoriatic arthritis are chronic inflammatory diseases of unknown etiology, affecting 2-3% of the world population. Initially, psoriasis was thought to be a hyper-proliferation disorder of keratinocytes only, but as time passed, the role of immune system became more evident and now both diseases are considered autoimmune disorders. In last few years, the discovery of interleukin (IL)-23/Th17 axis in pathophysiology of psoriatic diseases shifts the cytokine paradigm from Th1 to Th17 cytokines, focused mainly on IL-17 and IL-22. Therapeutic experiences strongly support the use of cytokine antagonists as an important modality in the treatment of psoriatic arthritis and plaque psoriasis. Studies examining these therapeutic agents which target different steps of the psoriatic inflammatory cascade have also shown significant efficacy. The relatively new IL-23/Th17 axis in psoriatic diseases got more importance with the success of ustekinumab, a new monoclonal antibody against IL-12 and IL-23. In IL-17 and IL-22 knock-out and transgenic mouse models, it has been found that recombinant IL-23 fails to produce epidermal hyperplasia which resembles psoriasis. Also, some success in animal models of psoriasis was found with anti IL-17A and anti IL-22. More studies are needed to validate the efficacy and safety of these cytokine antagonists in psoriatic diseases. Using a historical perspective and a chess game as an analogy, the main objective of this review is to summarize the central role of some of these cytokines in psoriasis pathophysiology and to develop a strategic approach to new therapeutic weapons within the armamentarium of psoriasis treatment.