‘Prototypical’ proinflammatory cytokine (IL-1) in multiple sclerosis: role in pathogenesis and therapeutic targeting

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalExpert Opinion on Therapeutic Targets
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 2 2020

Keywords

  • demyelination
  • IL-1R
  • IL-1ra
  • IL-1α
  • IL-1β
  • neurodegeneration
  • neuroinflammation
  • proinflammatory cytokines
  • synaptopathy

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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