Cannabidiol treatment increased the production of inflammatory suppressor cells in mice, which reduced the clinical signs of MS.
Non-psychoactive cannabinoid (CBD) reduced the clinical signs of multiple sclerosis (MS) and delayed disease onset in an experimental autoimmune encephalomyelitis (EAE) mouse model, according to a new study published in Frontiers in Immunology.
Marijuana CBD has been reported to exhibit anti-inflammatory and neuroprotective effects, demonstrating a potential therapeutic benefit for individuals with autoimmune diseases, including MS. However, the mechanisms through which CBD affects neuroinflammation are unclear.
In the study, the researchers sought to identify the mechanisms through which CBD suppresses neuroinflammation in MS-like disease by evaluating the effects of treatment with CBD on EAE mice.
Using the mouse model, the researchers examined CBD-induced effects on autoimmune neuroinflammation. The researchers administered daily 20 mg/kg doses of CBD into the abdomen and continued treatment until the end of the study at day 25.
Compared with non-CBD-treated mice, those treated with CBD demonstrated reduced clinical signs of EAE, decreased T-cell infiltration, and reduced levels of pro-inflammatory cytokines, such as interleukin (IL)-17 and interferon-gamma. Notably, the researchers found that CBD treatment led to a significant increase in the production of myeloid-derived suppressor cells (MDSCs) in EAE mice.
Recent studies have suggested that MDSCs play a critical role in suppressing neuroinflammation. To investigate whether CBD’s effects were linked to the induction of the inflammatory suppressor cells, the researchers analyzed the abdominal region of the mice.
The researchers observed a profound increase in the inflammatory-suppressor cells at both day 10 and 12 of treatment in the location of CBD administration. However, the number of MDSCs was lower in the spinal cord and brain of CBD-treated mice compared with untreated mice. In in vitro experiments, MDSCs were found to inhibit the proliferation of T-cells. Furthermore, the researchers showed that injecting purified CBD-induced MDSCs into EAE mice slowed disease progression, according to the study.
“Together, these studies demonstrate for the first time that CBD treatment may ameloriate EAE through induction of immunosuppressive MDSCs,” the researchers wrote.
To further confirm the role of MDSCs, the researchers evaluated the effect of MDSC depletion. In this experiment, CBD successfully attenuated disease progression as seen before, and MDSC depletion was observed to reverse this effect.
“Our studies provide further evidence of the importance of MDSCs and that manipulation of such cells may constitute novel therapeutic modality to treat MS and other autoimmune diseases,” the researchers concluded in the study.
Reference
Elliot DM, Singh H, Nagarkatti M, et al. Cannabidiol attenuates experimental autoimmune encephalomyelitis model of multiple sclerosis through induction of myeloid-derived suppressor cells. Frontiers in Immunology. 2018. https://doi.org/10.3389/fimmu.2018.01782