Cytokine Targeting in Psoriasis and Psoriatic Arthritis Beyond TNFa

I.B. Mclnnes

2.1 Introduction 30

2.2 Interleukin-15 31

2.2.1 Basic Biology 31

2.2.2 Immunologic Activities of IL-15 33

2.3 IL-15 in Chronic Inflammation 35

2.4 IL-15 in Psoriasis and Psoriatic Arthritis 37

2.5 Conclusion 39

References 40

Abstract. Targeting TNFa provided proof of concept for the role of proinflammatory cytokines in promoting cutaneous inflammation, particularly psoriasis. Recent studies have elucidated the presence of numerous cytokine and chemokine activities in psoriatic skin and synovium. There is considerable interest in the potential of such activities as novel therapeutic targets. IL-15 is an innate response cytokine that activates leukocyte subsets via binding to its unique IL-15Ra and shared P and y chain receptors. IL-15 promotes T cell memory and sustains local T cell activation, in part via prevention of apoptosis and mediates activation of monocytes, neutrophils and NK cells. IL-15 is up-regulated in psoriatic skin and psoriatic arthritis synovium. IL-15 blockade in a murine model of psoriasis led to marked suppression of typical psoriatic skin features. Clinical intervention in other chronic inflammatory disease states is now ongoing with encouraging early efficacy, raising the possibility for the first time of targeting this novel inflammatory moiety in psoriasis.

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