Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R(+)WIN55,212
J. Ludovic Croxford, Stephen D. Miller
J. Ludovic Croxford, Stephen D. Miller
Published April 15, 2003
Citation Information: J Clin Invest. 2003;111(8):1231-1240. https://doi.org/10.1172/JCI17652.
View: Text | PDF
Article Autoimmunity

Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R(+)WIN55,212

Abstract

Theiler murine encephalomyelitis virus–induced demyelinating disease (TMEV-IDD) is a mouse model of chronic-progressive multiple sclerosis (MS) characterized by Th1-mediated CNS demyelination and spastic hindlimb paralysis. Existing MS therapies reduce relapse rates in 30% of relapsing-remitting MS patients, but are ineffective in chronic-progressive disease, and their effects on disability progression are unclear. Experimental studies demonstrate cannabinoids are useful for symptomatic treatment of spasticity and tremor in chronic-relapsing experimental autoimmune encephalomyelitis. Cannabinoids, however, have reported immunosuppressive properties. We show that the cannabinoid receptor agonist, R(+)WIN55,212, ameliorates progression of clinical disease symptoms in mice with preexisting TMEV-IDD. Amelioration of clinical disease is associated with downregulation of both virus and myelin epitope-specific Th1 effector functions (delayed-type hypersensitivity and IFN-γ production) and the inhibition of CNS mRNA expression coding for the proinflammatory cytokines, TNF-α, IL1-β, and IL-6. Clinical trials investigating the therapeutic potential of cannabinoids for the symptomatic treatment of MS are ongoing, and this study demonstrates that they may also have potent immunoregulatory properties.

Authors

J. Ludovic Croxford, Stephen D. Miller

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Cannabinoid treatment increases the susceptibility of mice to TMEV infec...
Cannabinoid treatment increases the susceptibility of mice to TMEV infection and is not cytotoxic to splenocytes. R(+)WIN55,212 treatment of mice at the time of infection (a) (black bars) showed a significant increase in CNS virus titers compared with either S(–)WIN55,212 (gray bars) or untreated (white bars) TMEV-infected mice. Virus titers were not different from controls in mice treated with R(+)WIN55,212 at the onset of disease (b). *Significant increase in viral load in R(+)WIN55,212-treated mice compared with either S(–)WIN55,212 or untreated TMEV mice (P < 0.05). No PFUs were observed in naive mice. R(+)WIN55,212 treatment has no cytotoxic effect, as measured by FACS analysis of splenic CD4+, CD8+, B220+, and CD4+CD25+ lymphocytes, and F4/80+ macrophage populations compared with S(–)WIN55,212 or naive mice (c). Results are expressed as the mean total number of cells (n = 3 per group) ± SEM.