Novel Cannabinoid Suppresses TNF-α, IFN-α in Patients with Dermatomyositis
SAN FRANCISCO, CA—The synthetic, nonpsychoactive cannabinoid ajulemic acid shows early promise as a potential alternative therapy for dermatomyositis, according to a study reported at the 2015 ACR/ARHP Annual Meeting.
"Ajulemic acid may offer a novel, and potentially less toxic, treatment for dermatomyositis than the currently available therapies," Elizabeth S. Robinson, BSE, Philadelphia Veterans Affairs Medical Center, Philadelphia, and colleagues reported.
Dermatomyositis is an autoimmune disease with cutaneous symptoms frequently accompanied by inflammatory muscle and/or lung disease. In vitro, ajulemic acid has been shown to suppress secretion of TNF-α and IFN-α, two pro-inflammatory cytokines implicated in the disease's pathogenesis, from peripheral bloodstream mononuclear cells (PMBCs).
To assess ajulemic acid 's promise against dermatomyositis, the study authors isolated PBMCs from the blood of 17 patients diagnosed with dermatomyositis treated with 0, 3, 10 and 15µM concentrations of ajulemic acid and incubated at 37°C and 5.0% CO2 for 18 hours, “both with and without lipopolysaccharide in the case of TNF-α and with and without CpG oligonucleotides (CpG) in the case of IFN-α,” they noted.
Lipopolysaccharide and CpG were used “to stimulate secretion of TNF-α and IFN-α, respectively, in order to ensure sufficient production for quantifying the effects of ajulemic acid via ELISA,” they noted. TNF-α secretion values below 2pg/mL were excluded from analysis as outliers.
The lipopolysaccharide-stimulated PBMCs treated with ajulemic acid at concentrations of 0 (n=17), 3 (n=16), 10 (n=16) and 15 (n=15) μM secreted mean (standard deviation [SD]) TNF-α values of 7.37 (1.33), 7.73 (1.03), 5.60 (1.91) and 4.20 (1.92) pg/mL, respectively.
Ajulemic acid was found to suppress secretion of TNF-α from lipopolysaccharide-stimulated PBMCs at 10μM (P=0.0115) and 15μM (P<0.0001), but not at 3μM (P=0.9098), when compared to LPS-stimulated PBMCs not incubated with the agent, they reported.
Unstimulated PBMCs treated with ajulemic acid 0 (n=16), 3 (n=12), 10 (n=15) and 15 (n=12) μM secreted mean (SD) log TNF-α levels of 1.44(1.76), 1.97 (1.96), 1.09 (1.70) and 0.77 (1.48) pg/mL, respectively.
"ANOVA analysis found no statistically significant difference between these means (P=0.0965)," Robinson noted.
CpG-stimulated PBMCs that were not treated with ajulemic acid secreted a mean (SD) quantity of log IFN-α values of 5.89 (0.14) pg/mL in the 2 healthy control subjects, 5.33 (0.77) pg/mL in 8 patients with dermatomyositis not on antimalarials, and 0.42 (1.64) pg/mL in 7 patients on antimalarials.
More IFN-α was produced in patients with dermatomyositis not taking antimalarials (P<0.0001) and in healthy controls (P=0.0002) compared with those on antimalarials, they concluded.