The Endocannabinoid System: a new anti-inflammatory target in rheumatoid arthritis

Boon Chin Tan, EK Murray, Steven Watterson, H. Denis Alexander, David Gibson

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review


Rheumatoid arthritis (RA) is characterised by the loss of regulatory T cell (Treg) mediated suppression of inflammatory T helper cells. RA patients with loss of immune tolerance display elevated levels of circulating pro-inflammatory cytokines. The endocannabinoid system (ES) present on immune cells may represent a novel target for development of anti-inflammatory treatments. We screened the therapeutic potential of a phytocannabinoid compound, GL1b, in an ex vivo, peripheral blood mononuclear cell (PBMC) inflammatory model. PBMCs were cultured with CD3/CD28 and IL-2 to activate and expand T cells. Inflammation was induced by phorbol 12-myristate-13-acetate (PMA)/ionomycin activation, over 4 hours. Inflamed PBMCs were treated with 0, 10, 20 and 50 μM GL1b for 24 hours, then harvested for flow cytometry analysis of Tregs. Cytokine mRNA expression and conditioned media concentration were analysed with qRT-PCR and ELISA, respectively. Results will be fed into in silico model. 50 μM GL1b significantly suppressed the total Treg population (p<0.05), and relative numbers of CD69+, FOXP3+ and CTLA4+ Treg subpopulations decreased in a dose-responsive manner. A trend toward increased mean fluorescent intensity (MFI) of FOXP3 and CTLA4 was observed at 10 μM, relative to vehicle. A significant (p<0.01) decrease was observed in IL-6 mRNA relative to vehicle with 50 μM GL1b, whereas at 10 – 20 μM concentrations, a trend toward lower IL-6, TNFα, IL-10 expression was evident. Conversely, secreted cytokine concentrations were increased at 10 – 20 μM GL1b, relative to vehicle. Although the phytocannabinoid GL1b reduces the overall Treg population, activated and suppressive Treg subpopulations are elevated and cytokine gene expression reduced.
Original languageEnglish
Title of host publicationJournal of Immunology
Place of PublicationUSA
Publication statusPublished (in print/issue) - 1 May 2020
EventThe American Association of Immunologists - Hawaii, Honolulu, United States
Duration: 8 May 202012 May 2020


ConferenceThe American Association of Immunologists
Country/TerritoryUnited States
Internet address


Dive into the research topics of 'The Endocannabinoid System: a new anti-inflammatory target in rheumatoid arthritis'. Together they form a unique fingerprint.

Cite this