高CBD提取物（CBD-X）在哮喘管理中的作用：降低Th2驱动的细胞因子分泌和中性粒细胞/嗜酸性粒细胞活性
2024/10/29
摘要
背景与目标：哮喘是一种慢性气道炎症性疾病，影响全球10%以上的人口。其特征是气道炎症、黏液高分泌和支气管高反应性，在一部分患者中主要由2型辅助性T细胞（Th2）和2型固有淋巴样细胞（ILC2s）驱动。然而，相当一部分“低2型”哮喘患者表现为标准吸入型皮质类固醇（ICS）治疗困难。因此，开发创新的治疗策略变得至关重要。最近的研究表明大麻二酚（CBD）是一种很有前景的抗炎剂，能够调节免疫反应。本研究探讨了高CBD提取物（CBD-X）在哮喘中的治疗潜力。
方法：我们使用原代人Th2细胞、中性粒细胞和哮喘小鼠模型评估CBD-X对参与哮喘发病的细胞的影响。
结果：CBD-X提取物可抑制Th2细胞分化，减少IL-5和IL-13的分泌，而IL-5和IL-13是哮喘的关键细胞因子。此外，CBD-X显著降低了中性粒细胞中的促炎细胞因子IL-8和IL-6，并使它们的迁移受损，这是气道炎症的关键步骤。在小鼠哮喘模型中，CBD-X给药导致IgE和促哮喘细胞因子显著下调，同时肺组织中白细胞、嗜酸性粒细胞和中性粒细胞浸润减少。
结论：这些结果表明，CBD-X提取物可以通过靶向关键炎症通路和调节免疫细胞行为，为治疗2型高和2型低哮喘提供一种新的和互补的方法。
High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity
Miran Aswad, Antonina Pechkovsky, Narmeen Ghanayiem, Haya Hamza, Yaniv Dotan, Igal Louria-Hayon
Abstract
Background/objectives: Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma.
Methods: We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model.
Results: Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues.
Conclusions: These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.
背景与目标：哮喘是一种慢性气道炎症性疾病，影响全球10%以上的人口。其特征是气道炎症、黏液高分泌和支气管高反应性，在一部分患者中主要由2型辅助性T细胞（Th2）和2型固有淋巴样细胞（ILC2s）驱动。然而，相当一部分“低2型”哮喘患者表现为标准吸入型皮质类固醇（ICS）治疗困难。因此，开发创新的治疗策略变得至关重要。最近的研究表明大麻二酚（CBD）是一种很有前景的抗炎剂，能够调节免疫反应。本研究探讨了高CBD提取物（CBD-X）在哮喘中的治疗潜力。
方法：我们使用原代人Th2细胞、中性粒细胞和哮喘小鼠模型评估CBD-X对参与哮喘发病的细胞的影响。
结果：CBD-X提取物可抑制Th2细胞分化，减少IL-5和IL-13的分泌，而IL-5和IL-13是哮喘的关键细胞因子。此外，CBD-X显著降低了中性粒细胞中的促炎细胞因子IL-8和IL-6，并使它们的迁移受损，这是气道炎症的关键步骤。在小鼠哮喘模型中，CBD-X给药导致IgE和促哮喘细胞因子显著下调，同时肺组织中白细胞、嗜酸性粒细胞和中性粒细胞浸润减少。
结论：这些结果表明，CBD-X提取物可以通过靶向关键炎症通路和调节免疫细胞行为，为治疗2型高和2型低哮喘提供一种新的和互补的方法。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Pharmaceuticals (Basel). 2024 Oct 17;17(10):1382. doi: 10.3390/ph17101382.)
(Pharmaceuticals (Basel). 2024 Oct 17;17(10):1382. doi: 10.3390/ph17101382.)
High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity
Miran Aswad, Antonina Pechkovsky, Narmeen Ghanayiem, Haya Hamza, Yaniv Dotan, Igal Louria-Hayon
Abstract
Background/objectives: Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma.
Methods: We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model.
Results: Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues.
Conclusions: These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.
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哮喘中气道上皮衍生警报素的调节：治疗靶点的展望
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β-葡聚糖纳米颗粒可通过抑制小鼠铁死亡及DNA损伤缓解哮喘急性发作
