Aswad Miran, Pechkovsky Antonina, Ghanayiem Narmeen, Hamza Haya, Dotan Yaniv, Louria-Hayon Igal
Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa 3109601, Israel.
Clinical Research Institute at Rambam (CRIR), Rambam Health Care Campus, Haifa 3109601, Israel.
Pharmaceuticals (Basel). 2024 Oct 17;17(10):1382. doi: 10.3390/ph17101382.
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.
We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model.
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.
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/目的:哮喘是一种气道慢性炎症性疾病,影响着全球超过10%的人口。其特征为气道炎症、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型固有淋巴细胞(ILC2)驱动。然而,相当一部分哮喘患者表现为“2型低”哮喘,通常对标准吸入性糖皮质激素(ICS)治疗无效。因此,开发创新的治疗策略变得至关重要。最近的研究强调大麻二酚(CBD)是一种有前景的能够调节免疫反应的抗炎剂。本研究调查了高CBD提取物(CBD-X)在哮喘治疗中的潜力。
我们使用原代人Th2细胞、中性粒细胞和哮喘小鼠模型评估了CBD-X对参与哮喘发病机制的细胞的影响。
我们的研究结果表明,CBD-X提取物抑制Th2分化并减少IL-5和IL-13的分泌,这两种细胞因子在哮喘中至关重要。此外,CBD-X显著降低中性粒细胞中促炎细胞因子IL-8和IL-6的水平,并损害其迁移,这是气道炎症中的关键步骤。在小鼠哮喘模型中,给予CBD-X导致IgE和促哮喘细胞因子显著下调,同时肺组织中的白细胞、嗜酸性粒细胞和中性粒细胞浸润减少。
这些结果表明,CBD-X提取物可以通过靶向关键炎症途径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补充方法。