Cannabidiol selectively modulates interleukin (IL)-1β and IL-6 production in toll-like receptor activated human peripheral blood monocytes. (December 2021)

• Record Type: Journal Article
• Authors: Sermet, Sera; Li, Jinpeng; Bach, Anthony; Crawford, Robert B.; Kaminski, Norbert E.
• Is Part Of: Toxicology. Volume 464(2021)
• Publication Date: 2021-12
• Subjects: 5-HT 5-hydroxytryptamine -- 7−COOH-CBD 7-carboxy cannabidiol -- ANOVA analysis of variance -- AP-1 activator protein 1 -- CB cannabinoid receptor -- CBD cannabidiol -- CpG ODN cytosine-phosphorothioate-guanine oligodeoxynucleotides -- DAMP damage-associated molecular pattern -- EAM experimental autoimmune myocarditis -- FSL-1 synthetic diacylated lipoprotein -- GPR55 G-protein coupled receptor 55 -- HBV hepatitis B virus -- HCV hepatitis C virus -- HIV human immunodeficiency disorder -- HKLM heat killed listeria monocytogenes -- HTLV human T-lymphotropic virus -- IFN-γ interferon gamma -- IL interleukin -- IP-10 interferon gamma-induced protein 10 -- IRF interferon regulating factor -- LMW low molecular weight -- LPS lipopolysaccharide -- MAPK mitogen-activated protein kinase -- MCP-1 monocyte chemoattractant protein 1 -- MyD88 myeloid differentiation factor 88 -- NF-κβ nuclear factor kappa-light-chain-enhancer of activated B cells -- NLRP3 NLR family pyrin domain containing 3 -- PAMP pathogen-associated molecular pattern -- PMA/Io phorbol 12-myristate 12-acetate/ionomycin -- poly(I:C) polyinosine-polycytidylic acid -- PPAR-γ peroxisome proliferator-activated receptor gamma -- PPR pattern recognition receptor -- R837 imiquimod -- RPMI Roswell Park Memorial Institute Medium -- TGF-β1 transforming growth factor beta 1 -- THC Δ9-tetrahydrocannabinol -- TIR toll/interleukin-1 receptor -- TLR toll-like receptor -- TNF-α tumor necrosis factor alpha -- TRIF TIR-domain-containing adapter-inducing interferon beta -- TRP transient receptor potential; Cannabidiol (CBD) -- Cannabinoid -- Monocyte -- TLR -- IL-1β -- IL-6; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2021.153016
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: Cannabidiol (CBD) is a major non-euphoric cannabis-derived compound that has become popular in its over-the-counter use. CBD possesses low affinity for cannabinoid receptors, while the primary molecular target(s) by which it mediates biological activity remain poorly defined. Individuals commonly self-medicate using CBD products with little knowledge of its specific immunopharmacological effects on the human immune system; however, research has established primarily in rodent models that CBD possesses immune modulating properties. The objective of this study was to evaluate whether CBD modulates the innate immune response by human primary monocytes activated through toll-like receptors (TLR) 1–9. Monocytes were activated through each TLR and treated with CBD (0.5–10 μM) for 22 h. Monocyte secretion profiles for 13 immune mediators were quantified including: IL-4, IL-2, IP-10, IL-1β, TNFα, MCP-1, IL-17a, IL-6, IL-10, IFNγ, IL-12p70, IL-8, and TGF-β1. CBD treatment significantly suppressed secretion of proinflammatory cytokine IL-1β by monocytes activated through most TLRs, apart from TLRs 3 and 8. Additionally, CBD treatment induced significant modulation of IL-6 production by monocytes activated through most TLRs, except for TLRs 1 and 3. Most other monocyte-derived factors assayed were refractory to CBD modulation. Overall, CBD selectively altered monocyte-derived IL-1β and IL-6 when activated through most TLRs. This study is of particular importance as it provides a direct and comprehensive assessment of the effects of CBD on TLR-activated primary human monocytes at a time when CBD containing products are being widely used by the public.