Role of Epithelium-Derived Cytokines in Atopic Dermatitis and Psoriasis: Evidence and Therapeutic Perspectives.

Sebastiano Gangemi,Francesco Borgia,Lucia Peterle,Paolo Custurone,Giovanni Pioggia

doi:10.3390/biom11121843

Abstract

Atopic dermatitis and psoriasis are two of the most common chronic skin conditions. Current target therapies represent viable and safe solutions for the most severe cases of these two dermatoses but, presently, several limitations exist in terms of efficacy and side effects. A new class of products, epithelium-derived cytokines (TSLP, IL-25, IL-33), show an increasing potential for use in target therapy for these patients, and demonstrate a direct link between a generalized inflammatory and oxidative stress status and the human skin. A review was conducted to better understand their role in the aforementioned conditions. Of these three molecules, TSLP led has been most often considered in studies regarding target therapies, and most of the results in the literature are related to this cytokine. These three cytokines share common stimuli and are linked to each other in both acute and chronic phases of these diseases, and have been challenged as target therapies or biomarkers of disease activity. The results lead to the conclusion that epithelium-derived cytokines could represent a therapeutic opportunity for these patients, especially in itch control. Furthermore, they might work better when paired together with currently available therapies or in combination with in-development treatments. Further studies are needed in order to verify the efficacy and safety of the biologic treatments currently under development.

Highlights

Atopic dermatitis (AD) consists of erythematous patches scattered over specific areas of the body which define its subtype and a constant, intensityvariable pruritus, which is enough to lower the overall quality of life of the patient [4,5]
Raimondo et al demonstrated that interleukin 33 (IL-33) from psoriatic plaques induces the release of a wide range of osteoclastogenic factors from the skin, such as RANKL, that promote monocyte differentiation in osteoclasts and other osteoclastogenic mediators that could act in a RANKL independent pathway. These results suggest a link between psoriatic cutaneous inflammation and the pathogenesis of psoriatic arthritis (PsA), explaining why in most cases Pso anticipates several decays in the onset of PsA [18]
The results suggest a good tolerability of etokimab, and a good profile of efficacy measured by the Eczema Area and Severity Index (EASI) score

Summary

Introduction

Atopic dermatitis and psoriasis represent a daily reminder for the patients and practitioners of the current limitations of treatments and understanding of their pathophysiology. Psoriasis (Pso), characterized by erythematous, scaly patches on the skin and affecting other body districts such as bones and accessory skin structures, presents comorbidities with seemingly unrelated non-skin conditions such as a metabolic syndrome, heart disease and psychiatric disorders [1,2]. Pso has been described as an inflammatory disorder in which oxidative stress, advanced glycosylation end-products (AGEs) and advanced oxidation protein products (AOPP) play a major role in cytokine secretion [3]. Atopic dermatitis (AD) consists of erythematous patches scattered over specific areas of the body which define its subtype and a constant, intensityvariable pruritus, which is enough to lower the overall quality of life of the patient [4,5]

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