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

Cannabidiol selectively modulates interleukin (IL)-1β and IL-6 production in toll-like receptor activated human peripheral blood monocytes.
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DOI:
10.1016/j.tox.2021.153016
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发表时间:
2021-12
期刊:
影响因子:
4.5
通讯作者:
Kaminski, Norbert E.
Kaminski, Norbert E.
中科院分区:
医学3区
文献类型:
--
作者:
Sermet, Sera;Li, Jinpeng;Bach, Anthony;Crawford, Robert B.;Kaminski, Norbert E.

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大麻二酚(CBD)是一种主要的非欣快性大麻衍生化合物,在非处方使用中已经变得很受欢迎。CBD对大麻素受体具有低亲和力,而CBD介导生物活性的主要分子靶点仍然不明确。个人通常使用CBD产品自我治疗,对其对人体免疫系统的特异性免疫药理作用知之甚少;然而,研究主要在啮齿动物模型中建立了CBD具有免疫调节特性。本研究的目的是评估CBD是否通过toll样受体(TLR) 1-9激活的人原代单核细胞调节先天免疫反应。通过每个TLR活化单核细胞,用CBD (0.5 ~ 10μ m)处理22小时。定量测定13种免疫介质的单核细胞分泌谱,包括:IL-4、IL-2、IP-10、IL-1β、TNFα、MCP-1、IL-17a、IL-6、IL-10、IFNγ、IL-12p70、IL-8和TGF-β1。除TLRs 3和TLRs 8外,通过大多数TLRs激活的单核细胞显著抑制促炎细胞因子IL-1β的分泌。此外,除TLRs 1和TLRs 3外,CBD处理诱导通过大多数TLRs激活的单核细胞显著调节IL-6的产生。大多数其他的单核细胞衍生因子对CBD的调节是难治的。总的来说,当通过大多数tlr激活时,CBD选择性地改变了单核细胞来源的IL-1β和IL-6。在公众广泛使用含CBD产品的情况下,本研究对CBD对tlr激活的人原代单核细胞的影响提供了直接和全面的评估,因此具有特别重要的意义。
Cannabidiol (CBD) is a major non-euphoric cannabis-derived compound that has become popular in its over-the-counter utilization. CBD possesses low affinity for cannabinoid receptors, while the primary molecular target(s) by which CBD 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 (0.5–10μM) for 22 hours. 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.
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