Article
Cannabinoids drive Th17 cell differentiation in patients with rheumatic autoimmune diseases
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Authors
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David Kofler
- Klinik I für Innere Medizin, Uniklinik Köln, Köln
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Konstantin Kotschenreuther
- Klinik I für Innere Medizin, Uniklinik Köln, Köln
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Iris Waqué
- Klinik I für Innere Medizin, Uniklinik Köln, Köln
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Shuaifeng Yan
- Klinik I für Innere Medizin, Uniklinik Köln, Köln
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Anja Meyer
- Klinik I für Innere Medizin, Uniklinik Köln, Köln
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Thom Haak
- Klinik I für Innere Medizin, Uniklinik Köln, Köln
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Julia Von Tresckow
- Klinik I für Innere Medizin, Uniklinik Köln, Köln
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Joanna Schiller
- Klinik I für Innere Medizin, Uniklinik Köln, Köln
| Published: | September 9, 2020 |
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Outline
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Introduction: The legalization of cannabinoids for medical use has reinforced their emerging role as a treatment of chronic pain in patients with rheumatic diseases [1]. While an immunosuppressive effect of cannabinoids has been postulated, it could not be confirmed in clinical trials, so far [2]. The aim of this study was to evaluate possible immune-modulatory effects of cannabinoids in patients with rheumatic autoimmune diseases.
Methods: We studied ex vivo Th17 cell frequencies in patients consuming cannabidiol (CBD) oil and analyzed the in vitro influence of CBD on Th17 cell differentiation. Peripheral blood mononuclear cells were isolated from 50 patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or systemic lupus erythematosus (SLE) and from 20 healthy controls. CD4+ T cells were purified using MACS technique and cultured in vitro for 48 hours in the presence of CBD. Cytokine expression in CD4+ T cells was analyzed by flow cytometry.
Results: In vitro cultivation in the presence of CBD significantly increased Th17 cell differentiation in CD4+ T cells from patients with rheumatic autoimmune diseases (6.54±0.52% in the CBD group vs. 3.27±0.23% in the vehicle control group; p<0.0001). In contrast, Th17 cell differentiation was suppressed in healthy individuals (1.86±0.25% in the CBD group vs. 3.62±0.32% in the control group; p=0.0002). Moreover, we analyzed Th17 cell frequencies before and after treatment with CBD oil. After 4-8 weeks of CBD treatment, the ex vivo Th17 cell frequencies increased significantly in patients with rheumatic autoimmune diseases (1.10±0.32% before vs. 4.52±1.34% after CBD treatment). To further assess the characteristics of the CBD induced Th17 cells, we analyzed their gene expression profile and discovered a significant increase in SGK1 expression. This is remarkable, as SGK1 is an important regulator of the reciprocal development of pro-inflammatory Th17 cells.
Conclusion: Th17 cell frequencies are reduced by CBD in healthy individuals and elevated by CBD in patients with rheumatic autoimmune diseases. This discrepancy could be explained by the fact that CBD activates a variety of pathways and receptors, which are differentially expressed in patients with autoimmune conditions. Our data suggest that CBD should be used with caution in patients with rheumatic autoimmune diseases.
Disclosures: The authors declare no conflict of interest.
References
- 1.
- Caulley L, Caplan B, Ross M. Medical marijuana for chronic pain. N Engl J Med. 2018;379(16):1575-7. DOI: 10.1056/NEJMclde1808149
- 2.
- Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatic arthritis. Rheumatology (Oxford). 2006;45(1):50-2. DOI: 10.1093/rheumatology/kei183
