‘Prototypical’ proinflammatory cytokine (IL-1) in multiple sclerosis: role in pathogenesis and therapeutic targeting
Alessandra Musella, Diego Fresegna, Francesca Romana Rizzo, Antonietta Gentile, Francesca De Vito, Silvia Caioli, Livia Guadalupi, Antonio Bruno, Ettore Dolcetti, Fabio Buttari, Silvia Bullitta, Valentina Vanni, Diego Centonze, Georgia Mandolesi
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.