Elsevier

Cytokine

Volume 61, Issue 3, March 2013, Pages 704-712
Cytokine

Review Article
Anti-cytokine therapy in the treatment of psoriasis

https://doi.org/10.1016/j.cyto.2012.12.027Get rights and content

Abstract

Psoriasis is a chronic, inflammatory skin disease with many associated co-morbidities including diabetes, hypertension, obesity, psoriatic arthritis, and cardiovascular disease. It has long been known that psoriasis is a T cell-mediate disease and recent findings further demonstrate the important roles of the Th17 and Th22 arms of the immune system in the pathogenesis of psoriasis. Our understanding of this disease has progressed greatly and agents that target the cytokines involved in disease activity are under development or currently being used to treat psoriasis. A comprehensive review of the literature for cytokine-targeted therapies, their safety concerns, and efficacy in psoriasis are discussed here.

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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