Article
Immunomodulatory effects of cannabidiol and delta9-tetrahydrocannabinol in PBMCs and PBMC/rheumatoid synovial fibroblast co-cultures
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Published: | September 14, 2021 |
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Introduction: In 2017, cannabis was legalized in Germany for medical use but studies supporting its use in rheumatic diseases are rare. The two main active ingredients of cannabis, delta tetrahydrocannabinol (THC) and cannabidiol (CBD) showed some effects in reducing pain in rheumatoid arthritis (RA) but it is still unclear whether the inflammatory response is modulated. In this study, we investigate the impact of THC and CBD in a rheumatoid synovial fibroblast (RASF)/PBMC co-culture system.
Methods: RASF and PBMCs were co-cultured for 7 days under varying activating conditions (IFN-γ, CpG DNA, anti IgM) with or without THC or CBD and cytokine production (TNF, IL-10 and IL-6), antibody production and immune cell composition was determined.
Results: When PBMCs without RASF were stimulated with the toll-like receptor 9 agonist CpG (5µg/mL), CBD (10µM) reduced IL-10 production (from 410 ± 388 pg/mL to 136 ± 49 pg/mL) .In contrast, when PBMCs were incubated with the B cell receptor stimulus anti IgM (mimicking polyclonal B cell activation with antigen) in the presence of RASF, IL-10 production was increased (from 279 ± 86 pg/mL to 536 ± 269 pg/mL), while TNF levels were unaltered. Furthermore, CBD (10µM) reduced CpG-stimulated (2.5µg/mL) TNF production by PBMCs when co-cultured with RASF (from 115 ± 91 pg/mL to 37 ± 12 pg/mL). THC also reduced CpG-induced (5µg/mL) IL-10 (from 410 ± 388 pg/mL to 188 ± 47 pg/mL) production but did not change TNF levels in PBMC monocultures. IL-6 levels were not modulated by THC or CBD. Preliminary results also show a modulation of antibody production by THC and CBD.
Conclusion: In this study we demonstrate immunmodulating effects of CBD and THC in a coculture setting mimicking joint pathology thus suggesting that phytocannabinoids should be further investigated as adjunct anti-inflammatory therapy in RA.
Disclosures: The authors have nothing to disclose.