3H-1, 2-Dithiole-3-Thione As a Novel Therapeutic Agent for the Treatment of Experimental Autoimmune Encephalomyelitis

Background: 3H-1,2-dithiole-3-thione (D3T), the simplest member of the sulfur-containing dithiolethiones, is found in cruciferous vegetables, and has been previously reported to be a potent inducer of antioxidant genes and glutathione biosynthesis by activation of the transcription factor Nrf2. D3T is a cancer chemopreventive agent and possesses anti-inflammatory properties. 

Objectives: The effect of D3T in the autoimmune inflammatory disease Multiple Sclerosis / Experimental Autoimmune Encephalomyelitis (EAE) is unknown. The present study is to investigate the therapeutic effect of D3T in EAE. 

Methods: C57BL/6 mice were subjected to EAE induction. EAE mice were administered with D3T before and after disease onset. The clinical scores of EAE mice were followed for a period of 30 days. Cell infiltrations of Th1 and Th17 cells were analyzed in the inflamed brains of EAE. The effects of D3T on dendritic cells and microglia were also evaluated.  

Results: Our results show D3T, administered post immunization, not only delays disease onset but also dramatically reduces disease severity in EAE. Strikingly, D3T, administered post disease onset of EAE, effectively prevents disease progression and exacerbation. Mechanistic studies revealed that D3T suppresses the expression of co-stimulatory molecules and production of pro-inflammatory cytokines by dendritic cells, inhibits pathogenic Th1 and Th17 differentiation, represses microglia activation and inflammatory cytokine expression, and promotes phase II enzyme induction in microglia. 

Conclusions: Our results indicate that D3T affects both innate and adaptive immune cells, and the protective effect of D3T in EAE might be attributed to its effects on modulating dendritic cell and microglia activation and pathogenic T cell differentiation.