'Prototypical' proinflammatory cytokine (IL-1) in multiple sclerosis: role in pathogenesis and therapeutic targeting. (2nd January 2020)

• Record Type: Journal Article
• Authors: Musella, Alessandra; Fresegna, Diego; Rizzo, Francesca Romana; Gentile, Antonietta; De Vito, Francesca; Caioli, Silvia; Guadalupi, Livia; Bruno, Antonio; Dolcetti, Ettore; Buttari, Fabio; Bullitta, Silvia; Vanni, Valentina; Centonze, Diego; Mandolesi, Georgia
• Is Part Of: Expert opinion on therapeutic targets. Volume 24:Number 1(2020:Jan.)
• Page Start: 37
• Page End: 46
• Publication Date: 2020-01-02
• Subjects: IL-1β -- IL-1α -- IL-1R -- IL-1ra -- proinflammatory cytokines -- synaptopathy -- neurodegeneration -- demyelination -- neuroinflammation; Drugs -- Research -- Periodicals; 615.072
• DOI: 10.1080/14728222.2020.1709823
• Languages: English
• ISSNs: 1744-7631

Abstract

ABSTRACT: Introduction : It has been recognized for about 20 years that interleukin (IL)-1 signaling is implicated in Multiple Sclerosis (MS), a disabling, chronic, inflammatory and neurodegenerative disease of the central nervous system (CNS). Only recently, multifaceted roles of IL-1 emerged in MS pathophysiology as a result of both clinical and preclinical studies. Notably, drugs that directly target the IL-1 system have not been tested so far in MS. Areas covered : Recent studies in animal models, together with the development of ex vivo chimeric MS models, have disclosed a critical role for IL-1 not only at the peripheral level but also within the CNS. In the present review, we highlight the IL-1-dependent neuropathological aspects of MS, by providing an overview of the cells of the immune and CNS systems that respond to IL-1 signaling, and by emphasizing the subsequent effects on the CNS, from demyelinating processes, to synaptopathy, and excitotoxicity. Expert opinion : Drugs that act on the IL-1 system show a therapeutic potential in several autoinflammatory diseases and preclinical studies have highlighted the effects of these compounds in MS. We will discuss why anti-IL-1 therapies in MS have been neglected to date.