HSV-1-mediated IL-1 receptor antagonist gene therapy ameliorates MOG35-55-induced experimental autoimmune encephalomyelitis in C57BL/6 mice

R. Furlan, A. Bergami, E. Brambilla, E. Butti, M. G. De Simoni, M. Campagnoli, P. Marconi, G. Comi, G. Martino

Research output: Contribution to journalArticle

Abstract

Primary proinflammatory cytokines, such as IL-1β, play a crucial pathogenic role in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE), and may represent, therefore, a suitable therapeutic target. We have previously established the delivery of anti-inflammatory cytokine genes within the central nervous system (CNS), based on intracisternal (i.c.) injection of non-replicative HSV-1-derived vectors. Here we show the therapeutic efficacy of i.c. administration of an HSV-1-derived vector carrying the interleukin-1receptor antagonist (IL-1ra) gene, the physiological antagonist of the proinflammatory cytokine IL-1, in C57BL/6 mice affected by myelin oligodendrocyte glycoprotein-induced EAE. IL-1ra gene therapy is effective preventively, delaying EAE onset by almost 1 week (22.4±1.4 days post-immunization vs 15.9±2.1 days in control mice; P=0.0229 log-rank test), and decreasing disease severity. Amelioration of EAE course was associated with a reduced number of macrophages infiltrating the CNS and in a decreased level of proinflammatory cytokine mRNA in the CNS, suggesting an inhibitory activity of IL-1ra on effector cell recruitment, as antigen-specific peripheral T-cell activation and T-cell recruitment to the CNS is unaffected. Thus, local IL-1ra gene therapy may represent a therapeutic alternative for the inhibition of immune-mediated demyelination of the CNS.

Original languageEnglish
Pages (from-to)93-98
Number of pages6
JournalGene Therapy
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2007

Keywords

  • Autoimmunity
  • EAE
  • Herpes simplex
  • IL-1
  • IL-1ra
  • MS

ASJC Scopus subject areas

  • Genetics

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