Department of Neural Sciences, Center for Substance Abuse, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Department of Medicine, Center for Translational Medicine & Division of Pulmonary, Allergy and Critical Care Medicine, Jane and Leonard Korman Lung Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Int J Mol Sci. 2023 Sep 20;24(18):14328. doi: 10.3390/ijms241814328.
In recent years, there has been increased accessibility to cannabis for recreational and medicinal use. Incidentally, there has been an increase in reports describing allergic reactions to cannabis including exacerbation of underlying asthma. Recently, multiple protein allergens were discovered in cannabis, yet these fail to explain allergic sensitization in many patients, particularly urticaria and angioedema. Cannabis has a rich chemical profile including cannabinoids and terpenes that possess immunomodulatory potential. We examined whether major cannabinoids of cannabis such as cannabidiol (CBD) and the bicyclic sesquiterpene beta-caryophyllene (β-CP) act as contact sensitizers. The repeated topical application of mice skin with β-CP at 10 mg/mL (50 µL) induced an itch response and dermatitis at 2 weeks in mice, which were sustained for the period of study. Histopathological analysis of skin tissues revealed significant edema and desquamation for β-CP at 10 mg/mL. For CBD and β-CP, we observed a dose-dependent increase in epidermal thickening with profound thickening observed for β-CP at 10 mg/mL. Significant trafficking of CD11b cells was observed in various compartments of the skin in response to treatment with β-CP in a concentration-dependent manner. Mast cell trafficking was restricted to β-CP (10 mg/mL). Mouse proteome profiler cytokine/chemokine array revealed upregulation of complement C5/5a (anaphylatoxin), soluble intracellular adhesion molecule-1 (sICAM-1) and IL-1 receptor antagonist (IL-1RA) in animals dosed with β-CP (10 mg/mL). Moreover, we observed a dose-dependent increase in serum IgE in animals dosed with β-CP. Treatment with β-CP (10 mg/mL) significantly reduced filaggrin expression, an indicator of barrier disruption. In contrast, treatment with CBD at all concentrations failed to evoke scratching and dermatitis in mice and did not result in increased serum IgE. Further, skin tissues were devoid of any remarkable features, although at 10 mg/mL CBD we did observe the accumulation of dermal CD11b cells in skin tissue sections. We also observed increased filaggrin staining in mice repeatedly dosed with CBD (10 mg/mL). Collectively, our studies indicate that repeated exposure to high concentrations of β-CP can induce dermatitis-like pathological outcomes in mice.
近年来，人们越来越容易获得大麻作为娱乐和药用。顺便说一句，描述对大麻过敏反应的报告也有所增加，包括潜在哮喘恶化。最近，在大麻中发现了多种蛋白质过敏原，但这些并不能解释许多患者的过敏致敏，特别是荨麻疹和血管性水肿。大麻具有丰富的化学特征，包括大麻素和萜烯，具有免疫调节潜力。我们研究了大麻中的主要大麻素，如大麻二酚（CBD）和双环倍半萜β-石竹烯（β-CP）是否作为接触致敏剂。重复将 10mg/mL（50μL）β-CP 涂抹于小鼠皮肤可在 2 周内引起瘙痒反应和皮炎，且在研究期间持续存在。皮肤组织的组织病理学分析显示，10mg/mL 的β-CP 有明显的水肿和脱屑。对于 CBD 和 β-CP，我们观察到随着剂量的增加，表皮增厚，β-CP 可显著增厚。在 10mg/mL 的β-CP 浓度依赖性方式下，观察到 CD11b 细胞在皮肤的各种部位的显著迁移。肥大细胞迁移仅限于β-CP（10mg/mL）。小鼠蛋白质组生物标记物细胞因子/趋化因子分析显示，用β-CP（10mg/mL）处理后，动物补体 C5/5a（过敏毒素）、可溶性细胞间黏附分子-1（sICAM-1）和白细胞介素-1 受体拮抗剂（IL-1RA）上调。此外，我们还观察到用β-CP 处理的动物的血清 IgE 呈剂量依赖性增加。用β-CP（10mg/mL）治疗显著降低了丝聚合蛋白的表达，这是屏障破坏的指标。相反，用 CBD 治疗在所有浓度下都不能引起小鼠搔抓和皮炎，也不会导致血清 IgE 增加。此外，皮肤组织没有任何明显特征，尽管在用 10mg/mL CBD 治疗时，我们确实观察到皮肤组织切片中真皮 CD11b 细胞的积累。我们还观察到用 CBD（10mg/mL）重复治疗的小鼠丝聚合蛋白染色增加。总的来说，我们的研究表明，反复暴露于高浓度的β-CP 可在小鼠中引起类似皮炎的病理结果。
