Figure 4.
Signaling through the CB2R by THC mitigates the severity of acute GVHD. (A) Endocannabinoid levels of AEA and 2-AG in the liver, lung, colon, and spleen of lethally irradiated Balb/c mice receiving transplants of B6 BM alone or together with B6 spleen cells (adjusted to yield an αβ T-cell dose of 0.6 × 106 cells) and then undergoing assessment 14 days posttransplantation. Data are from 3 experiments, with 14 to 15 mice per group. AEA and 2-AG levels in the same tissues from naïve nontransplanted Balb/c mice are also depicted (n = 10). Data are presented as mean ± standard deviation. (B) Lethally irradiated Balb/c mice received transplants of B6 BM and spleen cells (adjusted to yield an αβ T-cell dose of 0.85 × 106 to 0.90 × 106 cells) and were then treated with a vehicle control (n = 20) or the CB2R agonist JWH-133 at a low (1.5 mg/kg; n = 10) or high dose (20 mg/kg; n = 10) for 14 consecutive days beginning on day 0. Balb/c mice receiving transplants of B6 BM alone served as controls (n = 12). Overall survival is depicted. Data are cumulative results from 4 experiments. (C) Irradiated Balb/c mice received transplants of B6 BM and spleen cells and were then treated with a vehicle control (n = 10) or the CB2R agonist JWH-133 (1.5 mg/kg; n = 10) for 35 consecutive days beginning on day 0. Balb/c mice receiving transplants of B6 BM alone served as controls (n = 6). Results are from 2 experiments. (D) Lethally irradiated Balb/c recipients received transplants of B6 BM and spleen cells (adjusted to yield an αβ T-cell dose of 0.85 × 106 to 0.9 × 106 cells). Animals were then treated with THC (20 mg/kg; n = 20) or vehicle (n = 20) for 40 days beginning on day 0. Balb/c mice receiving transplants of B6 BM alone and treatment with either vehicle or THC served as controls (n = 12 per group). Data are from 4 experiments. (E) Irradiated Balb/c mice received transplants of CB2R−/− BM alone (n = 6) or together with CB2R−/− spleen cells (adjusted to yield an αβ T-cell dose of 0.85 × 106 to 0.9 × 106 cells). Animals that received adjunctive spleen cells were treated with either THC (n = 10) or a vehicle control (n = 10) daily beginning on day 0 until death. Survival is depicted. Data are from 2 experiments. *P < .05, ****P < .0001.

Signaling through the CB2R by THC mitigates the severity of acute GVHD. (A) Endocannabinoid levels of AEA and 2-AG in the liver, lung, colon, and spleen of lethally irradiated Balb/c mice receiving transplants of B6 BM alone or together with B6 spleen cells (adjusted to yield an αβ T-cell dose of 0.6 × 106 cells) and then undergoing assessment 14 days posttransplantation. Data are from 3 experiments, with 14 to 15 mice per group. AEA and 2-AG levels in the same tissues from naïve nontransplanted Balb/c mice are also depicted (n = 10). Data are presented as mean ± standard deviation. (B) Lethally irradiated Balb/c mice received transplants of B6 BM and spleen cells (adjusted to yield an αβ T-cell dose of 0.85 × 106 to 0.90 × 106 cells) and were then treated with a vehicle control (n = 20) or the CB2R agonist JWH-133 at a low (1.5 mg/kg; n = 10) or high dose (20 mg/kg; n = 10) for 14 consecutive days beginning on day 0. Balb/c mice receiving transplants of B6 BM alone served as controls (n = 12). Overall survival is depicted. Data are cumulative results from 4 experiments. (C) Irradiated Balb/c mice received transplants of B6 BM and spleen cells and were then treated with a vehicle control (n = 10) or the CB2R agonist JWH-133 (1.5 mg/kg; n = 10) for 35 consecutive days beginning on day 0. Balb/c mice receiving transplants of B6 BM alone served as controls (n = 6). Results are from 2 experiments. (D) Lethally irradiated Balb/c recipients received transplants of B6 BM and spleen cells (adjusted to yield an αβ T-cell dose of 0.85 × 106 to 0.9 × 106 cells). Animals were then treated with THC (20 mg/kg; n = 20) or vehicle (n = 20) for 40 days beginning on day 0. Balb/c mice receiving transplants of B6 BM alone and treatment with either vehicle or THC served as controls (n = 12 per group). Data are from 4 experiments. (E) Irradiated Balb/c mice received transplants of CB2R−/− BM alone (n = 6) or together with CB2R−/− spleen cells (adjusted to yield an αβ T-cell dose of 0.85 × 106 to 0.9 × 106 cells). Animals that received adjunctive spleen cells were treated with either THC (n = 10) or a vehicle control (n = 10) daily beginning on day 0 until death. Survival is depicted. Data are from 2 experiments. *P < .05, ****P < .0001.

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