Table 1.
The effects of cannabinoids and agonists/antagonists of CBR-1/2 on immune cells.
| Component | Cell Type/Animal Model | Experimental Design | Effects | Reference |
|---|---|---|---|---|
| THC | Human T cells, B cells, and DCs | Ex vivo | Increased apoptosis | [102] |
| THC | BALB/c mice | Ex vivo | Suppressed the proliferation of spleen and lymph node cells | [116] |
| THC/CBD | Human T cells, B cells, eosinophils, CD-8, and NK cells |
In vitro | Decreased cytokine production | [106] |
| THC | Splenocytes derived from BALB/c mice | Ex vivo | Decreased the production of Th1-associated cytokines, including g IL-2, IL-12, and interferon-g (IFN-g), increasing the production of Th2 related cytokines, such as IL-4 and IL-10 | [117] |
| THC | Splenocytes from C3H/HeJ mice | Ex vivo | Suppressed cloned cell line with NK-cell activity | [133] |
| THC | Splenocytes from C3H/HeJ mice | In vivo and ex vivo | Suppressed NK-cell activity | [134] |
| THC | Splenocytes from C57Bl/6 mice or CB1−/− CB2−/− C57Bl/6 |
Ex vivo | Suppressed the function of CTLs independent of CB1-R and CB2-R | [138] |
| THC | C3H/HeN mice or splenocytes derived from C3H/HeN mice | In vivo and in vitro | Suppressed the induction and cytolytic activity of CTLs | [139] |
| THC | Murine peritoneal macrophages (B6C3)F1 and C57BL/6 mice | Ex vivo | Inhibited migration (CB-R dependent) | [158] |
| THC | Bone marrow-derived cells from C57BL/6 mice | Ex vivo | Induced the NF-kappaB-dependent apoptosis of DC’s through CBR-1 and CBR-2 | [104] |
| THC | Bone-marrow-derived cells from BALB/c mice | Ex vivo | Inhibited the expression of MHCII and costimulatory molecules CD40 and CD86 and poor stimulation of CD4 T cells to legionella–pneumonia-loaded DCs | [167] |
| THC | MDSC cells derived from BL6 mice | In vivo | Induced MDSCs by epigenetic changes that reduce the expression of DNMT3a and DNMT3b and increased the expression of Arg1 and STAT3 | [188] |
| THC | C57BL/6 mice or purified peritoneal CD11b+Gr-1+ cells from C57BL/6 | In vivo and in vitro | Induced MDSC cells and their expansion to the periphery by increasing G-CSF dependently on CB1-R and CB2-R | [187] |
| CBN | EL-4 cell line | In vitro | Increased IL-2 in activated T cells (CB1-R and CB2-R independent) | [112] |
| CBD | Splenocytes derived from C57BL/6 mice | In vitro | Induced CD4+ CD25+ T-regs to robustly suppress responder T-cell proliferation | [124] |
| CBD | Male BALB/c mice | Ex vivo | Increased apoptosis of thymocytes by increasing ROS generation | [120] |
| CBD | EL-4 thymoma cell line | In vitro | Increased apoptosis by increasing ROS generation | [120] |
| CBD | Male adult Wistar rat | In vivo | Reduce production of serum cytokines | [105] |
|
Cannabis sativa L. extract 5% CBD |
Human neutrophil | In vitro | Decreased migration, ROS generation, and TNF-α production | [107] |
| CBD | Splenic T cells derived from B6C3F1 or C57BL/6 mice | Ex vivo | Reduced IL-2 and IFN-γ cytokines production | [112] |
| CBD | Splenocytes derived from C57BL/6 | Ex vivo | Increased apoptosis of T cells and B cells | [144] |
| CBD | BALB/c mice or splenocytes derived from BALB mice | In vivo and ex vivo | Suppressed antigen-specific antibody in OVA-sensitized mice and decreased production of IL-2, IL-4, and IFN-γ | [147] |
| CBD | Peritoneal macrophages derived from NOD/LtJ mice (model for diabetes) | Ex vivo | Reduction in plasma levels of the pro-inflammatory cytokines, IFN-g and TNF-a and increased levels of anti-inflammatory cytokine IL-4 and IL-10. | [162] |
| CBD | Human monocytes | Ex vivo | Increased apoptosis | [164] |
| CBD | Female C57BL/6 mice and C3H/HeJ mice | In vitro | Induction of immunosuppressive CD11b+ Gr-1+ MDSC in naive mice dependently on mast cells and primarily mediated by PPAR-g | [190] |
| Delta8-THC, CBD, and CB2-R agonist (HU-308). | BALB/c and CBR2−/− mice (model for corneal injury) | In vivo | Reduced neutrophil infiltration to the cornea. The anti-inflammatory effect of delta8-THC is dependent on CBR-1, whereas that of CBD and HU-308 is dependent on CB2-R. | [152] |
| CB2-R agonist (JWH-015 and JWH-133) |
Human monocytes | Ex vivo | Reduced chemotactic response | [157] |
| CB2-R agonist (O-1966) |
Splenocytes from WT C57BL/6 mice or CB2-R knockout (CB2-R k/o) | Ex vivo | Decreased levels of NF-κB and NFAT, and increased levels of IL-10 expression in WT T cells, but not in T cells from CB2R k/o mice. Additionally, increased levels of T-regs. | [126] |
| CB1-R antagonist (SR 141716) /CB2-R (SR144528) antagonist |
Splenocytes derived from Male Swiss mice | Ex vivo | Reversed the INF-(g) reduction in NK cells induced by delta9-THC | [136] |
| CB2-R agonist (JWH-133) | Bone-marrow-derived cells from male C57BL/6 mice and CB1−/− and CB2−/− mice | Ex vivo | Inhibited neutrophil recruitment to the brain and protection against ischemic brain injury | [150] |
| CB1-R agonist (ACEA), CB2 (JWH015), and antagonists of both receptors | Peritoneal macrophages derived from C57BL/6J WT and CB2−/− mice or RAW264.7 | In vitro and ex vivo | CB1-R agonist increased ROS production and activation of CB2-R negatively regulated the process | [161] |
| CB1-R agonist (ACPA) and antagonist (AM251) | Bone-marrow-derived cells from C57BL/6 mice |
Ex vivo | ACPA showed a reduction in MHC-II cell surface expression and reduced the T cell stimulatory capacity of DC | [168] |
| CB1-R agonist (WIN55212-2) | Human DCs | Ex vivo | Inhibits inflammatory signaling pathway and promote autophagy | [169] |
| CB2-R agonist (JW-113) |
C57Bl6/N mice (model of lung inflammation) |
In vivo | Induced migration and chemotaxis of eosinophils | [171] |
| CB agonist CP55,940 | Mast cells derived from Dunkin-Hartley guinea pigs | Ex vivo | Decreased mast cell activation in a manner dependent on CB2-R receptor | [173] |
| Bhang (marijuana) | Human NK cells, B cells, and, T cells derived from smokers as compared to control | In vivo | Significant decrease in the number of functional cells | [132] |
| Marijuana | Human alveolar macrophage cells derived from smokers | Ex vivo | Impaired alveolar macrophage function and cytokine production (g TNF-α and TGF-β) | [154] |