Review ArticleAnti-cytokine therapy in the treatment of psoriasis
Highlights
► Psoriasis is a Th17-mediated disease. ► Currently available psoriasis therapies target TNF-α and IL-12 and IL-23. ► Therapies targeting the Th17 pathway are currently in phase 3 studies.
Introduction
Psoriasis vulgaris is a chronic sometimes debilitating, disease characterized by thick, red, scaling plaques on the skin (Fig. 1). This clinical appearance is the result of premature keratinocyte cornification and increased keratinocyte proliferation in response to inflammatory and angiogenic stimuli in the skin. Psoriasis is a strongly T cell mediated disease and advances in knowledge of the immunologic basis of psoriasis have allowed the development of several targeted therapies for psoriasis.
Section snippets
Clinical background
Psoriasis affects up to 3% of the world’s population [1] and current estimates put the prevalence of psoriasis in the United States at about 7.5 million cases [2]. Psoriasis can occur at any age, however there is a bimodal peak in incidence in early adulthood (age 18–25) and in later adulthood (age 50–55) [3]. Both genders tend to be equally affected and psoriasis is seen across multiple ethnic and racial backgrounds. Psoriasis is responsible for significant health care costs, estimated to be
Cytokines in the pathogenesis of psoriasis
Psoriasis arises from an imbalance in both innate (TNF-α and IL-17) and adaptive (IL-23/Th17) immune responses [6], [7], [8], [9], [10], [11]. Following an environmental trigger one of the earliest events that occur in the initiation phase of psoriasis is the release of several innate inflammatory cytokines, including IL-1β, IL-6, and TNF-α. TNF-α is secreted by keratinocytes, inflammatory dendritic cells (DCs), mast cells, macrophages, and effector T cells [12], [13], [14]. Genomewide
Targeting cytokines to treat psoriasis
Mild psoriasis can be treated using topical therapies; primarily topical steroids, tar preparations, and ultraviolet light therapy. Systemic therapies are often needed, however, and can be divided into biologic therapy (molecules, usually monoclonal antibodies, which target a particular cytokine or receptor) and non-biologic therapy (other oral agents with various molecular targets). The cytokine pathways targeted in psoriasis therapies are illustrated in Fig. 3. Table 1 also summarizes these
Conclusions and future of psoriasis therapy
Elucidating the many cytokines involved in psoriasis has allowed the approach to treatment of this disease to evolve from a broad strategy of immunosuppression to the use and development of novel targeted therapies. However, disturbances in the homeostasis of the immune system can potentially result in adverse consequences such as infection and have somewhat unexpected effects such as cardiovascular disease. Further work is required to better understand the intricacies of the cytokine pathways
Acknowledgments
This work was supported by National Institutes of Health Grant 1K22 AI 83882-01 (A.R.M) and a National Psoriasis Foundation Discovery Research Grant (A.R.M).
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