Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice by inducing CD4+ T cell apoptosis

Journal of Neuroinflammation, 2020 · DOI: https://doi.org/10.1186/s12974-020-01829-x · Published: May 8, 2020

Simple Explanation

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by severe white matter demyelination. Arsenic trioxide (ATO) is an ancient Chinese medicine used for its therapeutic properties with several autoimmune diseases. This study assessed the therapeutic effects of ATO in EAE mice by evaluating differences in clinical symptoms, histology and microglial activation in the spinal cord, expression levels of inflammatory factors, and proportion of CD4+ T cells between ATO-treated and non-treated mice.

Study Duration

Not specified

Participants

Female C57BL/6 mice (6–8 weeks old, 20 ± 2 g)

Evidence Level

Not specified

Key Findings

1
ATO delayed the onset of EAE and alleviated the severity of EAE in mice.
2
Treatment with ATO also attenuated demyelination, alleviated inflammation, reduced microglia activation, and decreased the expression levels of IL-2, IFN-γ, IL-1β, IL-6, and TNF-α in EAE mice.
3
ATO induced CD4+ T cell apoptosis via the mitochondrial pathway both in vitro and in vivo.

Research Summary

This study explored the protective role of ATO on MOG35–55-induced EAE mice. The results suggested that ATO delayed the onset of EAE, alleviated the clinical signs and severity of EAE in mice, reduced neuroinflammation, and attenuated demyelination. The study indicated that ATO induced CD4+ T cell apoptosis through the mitochondrial pathway, thus inhibiting the infiltration of CD4+ T cells into the CNS, thereby delaying the onset of EAE and effectively reducing the severity of EAE in mice.

Practical Implications

Potential MS Treatment

ATO shows potential as a novel drug for treating MS by ameliorating EAE in mice.

Comorbidity Management

ATO's anti-tumor and anti-autoimmunity properties may benefit MS patients with comorbidities like cancer and autoimmune diseases.

Clinical Application Facilitation

The findings may facilitate the clinical application of ATO for treating MS or other autoimmune diseases.

Study Limitations

1
EAE mice developed a relatively mild monophasic disease course instead of the more severe chronic progressive form that is usually observed for such robust induction conditions.
2
Since EAE is initiated and orchestrated by autoreactive CD4+ T cells, we focused on the CD4+ T cells in both in vivo and in vitro experiments.
3
The effects of ATO on regulatory, anti-inflammatory cell types or cytokines in EAE mice may be a focus of our future studies.

Your Feedback

Was this summary helpful?

Back to Immunology