Anti-CCL2 treatment inhibits Theiler's murine encephalomyelitis virus-induced demyelinating disease.
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.
Karpus
William J
WJ
Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, Institute for Neuroscience, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA. w-karpus@northwestern.edu
Kennedy
Kevin J
KJ
Fife
Brian T
BT
Bennett
Jamie L
JL
Dal Canto
Mauro C
MC
Kunkel
Steven L
SL
Lukacs
Nicholas W
NW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D018188:Cardiovirus Infections / Q000276:immunology / Q000628:therapy*; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology / Q000628:therapy* / Q000821:virology; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D017945:Theilovirus / Q000254:growth & development*
D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2