Journal of NeuroVirology

, Volume 12, Issue 4, pp 251–261 | Cite as

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
Article

Abstract

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.

Keywords

cell trafficking chemokines demyelinating disease multiple sclerosis neuroimmunology Theiler’s virus 

Abbreviations

BHK-21

baby hamster kidney cell line 21

BSA

bovine serum albumin

CCL2

monocyte chemotactic protein-1

CCL3

macrophage inflammatory protein-1α

CCL4

macrophage inflammatory protein-1β

CCL5

RANTES

CNS

central nervous system

CXCL1

macrophage inflammatory protein-2

CXCL10

gamma interferon inducible protein-10

H&E

hematoxylin and eosin

NRS

normal rabbit serum

TMEV

Theiler’s murine encephalomyelitis virus

TMEV-IDD

Theiler’s murine encephalomyelitis virus—induced demyelinating disease

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Copyright information

© Journal of NeuroVirology, Inc. 2006

Authors and Affiliations

  • William J. Karpus
    • 1
  • Kevin J. Kennedy
    • 1
  • Brian T. Fife
    • 1
  • Jamie L. Bennett
    • 1
  • Mauro C. Dal Canto
    • 1
  • Steven L. Kunkel
    • 2
  • Nicholas W. Lukacs
    • 2
  1. 1.Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, Institute for NeuroscienceNorthwestern University, Feinberg School of MedicineChicagoUSA
  2. 2.Department of PathologyUniversity of Michigan Medical SchoolAnn ArborUSA

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