Dataset Information

Δ⁹-Tetrahydrocannabinol (THC) Impairs CD8⁺ T Cell-Mediated Activation of Astrocytes.

ABSTRACT: CD8⁺ T cells can contribute to neuroinflammation by secretion of inflammatory cytokines like interferon γ (IFNγ) and tumor necrosis factor α (TNFα). Astrocytes, a glial cell in the brain, can be stimulated by IFNγ and TNFα to secrete the inflammatory cytokines, monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and interferon-γ inducible protein 10 (IP-10). Δ⁹-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in Cannabis sativa, possesses potent anti-inflammatory activity. The objective of this investigation was to assess the effects of THC treatment on CD8⁺ T cell-mediated activation of astrocytes. CD3/CD28/IFNα- stimulated CD8⁺ T cells were treated with vehicle (0.03% EtOH) or THC and cocultured with U251 astrocytes. IP-10⁺, MCP-1⁺, and IL-6⁺ astrocytes were quantified by flow cytometry. LegendPlex™ was used to measure cytokine secretion by CD8⁺ T cells and flow cytometry was employed to quantify IFNγ, TNFα, and lysosomal-associated membrane protein 1 (LAMP-1) expression. Recombinant TNFα and IFNγ were used to stimulate MCP-1, IP-10, IL-6 responses in U251 astrocytes, which were measured by flow cytometry. Treatment with THC reduced CD8⁺ T cell-mediated induction of IP-10 and IL-6 responses in U251 astrocytes but had no effect on MCP-1. THC treatment differentially affected T cell effector functions such that IFNγ and degranulation responses were sensitive to THC-mediated ablation while TNFα was not. Lastly, THC treatment reduced the IFNγ-induced IP-10 response but had no effect on TNFα-induced MCP-1 response in U251 astrocytes. The results suggest that cannabinoid treatment can selectively reduce certain CD8⁺ T cell responses that contribute to stimulation of astrocytes. Graphical Abstract Treatment with THC can abate CD8⁺ T cell-dependent neuroinflammatory processes by inhibiting CD8⁺ cell differentiation into effector cells, suppressing CD8⁺ effector cell function, and reducing activation of astrocytes by CD8⁺ T cell-derived inflammatory cytokines.

SUBMITTER: Henriquez JE

PROVIDER: S-EPMC7529688 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Δ9-Tetrahydrocannabinol (THC) Impairs CD8+ T Cell-Mediated Activation of Astrocytes.

Henriquez Joseph E JE Bach Anthony P AP Matos-Fernandez Karina M KM Crawford Robert B RB Kaminski Norbert E NE

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 20200326 4

CD8+ T cells can contribute to neuroinflammation by secretion of inflammatory cytokines like interferon γ (IFNγ) and tumor necrosis factor α (TNFα). Astrocytes, a glial cell in the brain, can be stimulated by IFNγ and TNFα to secrete the inflammatory cytokines, monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and interferon-γ inducible protein 10 (IP-10). Δ9-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in Cannabis sativa, possesses potent an ...[more]

PMID: 32215844

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Project description:BackgroundThere is an expanding unregulated market for a psychotropic compound called ∆8-Tetrahydrocannabinol (delta-8-THC) that is being derived from hemp, but a summary of adverse events related to delta-8-THC has not been publicly reported.MethodsThis case series assessed adverse events reported by delta-8-THC users on the Reddit forum r/Delta8 and compared these to delta-8-THC AEs in the US Food and Drug Administration Adverse Event Reporting System (FAERS). Delta-8-THC and cannabis AEs reported in FAERS were also compared. The r/Delta8 forum was selected because it includes a large sample of 98,700 registered individuals who publicly discuss their experiences using delta-8-THC. All r/Delta8 posts were obtained from August 20, 2020, through September 25, 2022. A random sample of r/Delta8 posts was drawn (n = 10,000) and filtered for posts in which delta-8-THC users reported an adverse event (n = 335). FAERS reports that listed delta-8-THC (N = 326) or cannabis (N = 7076) as a suspect product active ingredient were obtained. Adverse events claimed to result from delta-8-THC use were coded using Medical Dictionary for Regulatory Activities to system organ class and preferred term categories.ResultsThe absolute number of delta-8-THC adverse event reports (N = 2184, 95% CI = 1949-2426) and serious adverse event reports (N = 437; 95% CI = 339-541) on r/Delta 8 were higher than the adverse event reports (N = 326) and serious adverse event reports (N = 289) to FAERS. Psychiatric disorders were the most frequently cited system organ class in r/Delta8 adverse event reports, mentioned in 41.2% (95% CI = 35.8%-46.3%) of reports, followed by respiratory, thoracic and mediastinal disorders (29.3%, 95% CI = 25.1%-34.0%) and nervous system disorders (23.3%, 95% CI = 18.5%-27.5%). Anxiety (16.4%, 95% CI = 12.8-20.6), Cough (15.5%, 95% CI = 11.9-20.0) and Paranoia (9.3%, 95% CI = 6.3-12.5) were the most frequently cited preferred terms in adverse event reports. The overall prevalence of AEs reported for cannabis and delta-8-THC on FAERS were also similar when analyzed by system organ class (Pearson's r = 0.88).ConclusionsThe findings of this case series suggest that most of the adverse events reported by delta-8-THC users are like those reported during acute cannabis intoxication. This finding suggests that health care professionals follow similar treatment and management protocols, and that jurisdictions should clarify whether delta-8-THC can be sold as a hemp product.

Dataset Information

Δ⁹-Tetrahydrocannabinol (THC) Impairs CD8⁺ T Cell-Mediated Activation of Astrocytes.

Publications

Δ<sup>9</sup>-Tetrahydrocannabinol (THC) Impairs CD8<sup>+</sup> T Cell-Mediated Activation of Astrocytes.

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