Anti-CCL2 treatment inhibits Theiler's murine encephalomyelitis virus-induced demyelinating disease

William J. Karpus, Kevin J. Kennedy, Brian T. Fife, Jamie L. Bennett, Mauro C. Dal Canto, Steven L. Kunkel, Nicholas W. Lukacs

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20 Scopus citations


Theiler's murine encephalomyelitis virus induces a demyelinating disease (TMEV-IDD) of the central nervous system (CNS) in susceptible mouse strains with accompanying histopathology characterized by mononuclear cell infiltrates. In susceptible strains of mice such as SJL, virus establishes a persistent infection in macrophages, induces a CNS infiltration by macrophages, T cells, and B cells, which results in chronic-progressive paralysis. In the present report the authors have investigated the functional role of CCL2 (monocyte chemotactic protein-1) in the induction and progression of demyelinating disease. Treatment of infected mice at day 0, 14, or 28 with anti-CCL2 resulted in a significant decrease in the clinical disease progression. Further analysis of anti-CCL2-treated mice revealed decreased CNS inflammation and mononuclear cell infiltration with an accompanying change in inflammatory cytokine responses. There was an overall decrease in the absolute numbers of CNS-infiltrating CD4+T cells, macrophages, and B cells. Finally, anti-CCL2 treatment resulted in decreased viral load in the CNS. These data directly demonstrate a role for CCL2 in the pathogenesis of TMEV-IDD.

Original languageEnglish (US)
Pages (from-to)251-261
Number of pages11
JournalJournal of neurovirology
Issue number4
StatePublished - Aug 2006


  • Cell trafficking
  • Chemokines
  • Demyelinating disease
  • Multiple sclerosis
  • Neuroimmunology
  • Theiler's virus


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