Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
DM is an autoimmune disease with cutaneous symptoms often accompanied by inflammatory muscle and/or lung disease. Current therapies for DM are often toxic and ineffective. Ajulemic acid (AJA) is a synthetic, non-psychoactive cannabinoid potentially useful for treating DM. Experiments presented here quantify the capacity of AJA to suppress the secretion of TNF-α and IFN-α, two pro-inflammatory cytokines implicated in the pathogenesis of DM, from the peripheral blood mononuclear cells (PBMCs) of DM patients.
PBMCs were isolated from the blood of 22 DM patients and then treated with 0, 3, 10 and 15 µM concentrations of AJA and incubated at 37°C and 5.0% CO2 for 18 hours both with and without lipopolysaccharide (LPS) in the case of TNF-α and with and without CpG oligonucleotides (CpG) in the case of IFN-α. LPS 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 AJA via ELISA. Statistical analyses were performed on TNF-α and IFN-α secretion values normalized by natural log transformation, and unstimulated TNF-α secretion values below 2 pg/ml were excluded from analysis as outliers.
The LPS-stimulated PBMCs treated with 0 (n=17), 3 (n=16), 10 (n=16) and 15 (n=15) μM AJA 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. There was a statistically significant difference between the means using one-way ANOVA analysis (p<0.0001). In the post hoc analysis, AJA suppressed the secretion of TNF-α from LPS-stimulated PBMCs at 10 μM AJA (adjusted p=0.0115) and 15 μM AJA (adjusted p<0.0001), but not at 3 μM AJA (adjusted p=0.9098), when compared to LPS-stimulated PBMCs not treated with AJA. Unstimulated PBMCs treated with 0 (n=11), 3 (n=9), 10 (n=9) and 15 (n=7) μM AJA secreted mean (SD) TNF-α values of 2.27 (1.40), 2.47 (1.75), 1.83 (1.57) and 0.14 (1.72) pg/ml, respectively. Analysis by one-way ANOVA found a statistically significant difference between the means (p=0.0303). In the post hoc analysis, AJA suppressed the secretion of TNF-α from unstimulated PBMCs at 15 μM AJA (adjusted p=0.0444), but not at 3 μM AJA (adjusted p=0.9925) or 10 μM AJA (adjusted p=0.9274), when compared to unstimulated PBMCs not treated with AJA.
CpG-stimulated PBMCs treated with 0 (n=8), 3 (n=7), 10 (n=8) and 15 (n=7) μM AJA secreted mean (SD) IFN-α values of 5.33 (0.77), 1.38 (2.19), 1.06 (0.78) and -0.03 (1.68) pg/ml, respectively. There was a statistically significant difference between the means using one-way ANOVA analysis (p<0.0001). In the post hocanalysis, AJA suppressed IFN-α secretion from CpG-stimulated PBMCs at 3 μM AJA (adjusted p=0.0004), 10 μM AJA (adjusted p=0.0010) and 15 μM AJA (adjusted p=0.0003) when compared to CpG-stimulated PBMCs not treated with AJA. Unstimulated PBMCs secreted too little IFN-α to test the effects of AJA.
AJA is a novel, non-psychoactive cannabinoid that suppressed secretion of TNF-α and IFN-α from the PBMCs of DM patients in vitro. Thus, AJA may offer patients with DM an effective therapy with less toxicity than other treatments currently available.
To cite this abstract in AMA style:Alves P, Robinson E, Bashir M, Feng R, Werth VP. Ajulemic Acid Is a Novel Cannabinoid That Suppresses the Secretion of TNF-α and IFN-α from the Peripheral Blood Mononuclear Cells of DM Patients In Vitro [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/ajulemic-acid-is-a-novel-cannabinoid-that-suppresses-the-secretion-of-tnf-and-ifn-from-the-peripheral-blood-mononuclear-cells-of-dm-patients-in-vitro/. Accessed October 22, 2017.
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