Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA.
Int Forum Allergy Rhinol. 2015 Jan;5(1):10-3. doi: 10.1002/alr.21436. Epub 2014 Oct 20.
Verapamil is an L-type calcium channel blocker (CCB) that has been shown to have immunomodulatory properties in a variety of tissues. The goal of this study was determine whether verapamil is capable of regulating cytokine secretion in sinonasal polyps and to compare this effect to dexamethasone, an established immunosuppressive corticosteroid.
This was an institutional review board (IRB)-approved study in sinonasal polyp explants derived from 8 patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyps were incubated with dexamethasone or verapamil for 24 hours followed by an additional 24 hours with Staphylococcal enterotoxin B (SEB). Concentrations of secreted cytokines over each exposure period were determined by enzyme-linked immunosorbent assay (ELISA) and are expressed as a percent. Results were compared using a 2-tailed Student t test.
The percent of SEB-stimulated interleukin-5 (IL-5) secretion (mean ± standard deviation [SD], 339.94% ± 315.48%) between the second and first treatment periods was significantly reduced following exposure to dexamethasone (74.08% ± 26.77%, p < 0.05) and verapamil (119.99% ± 69.32%, p < 0.05). The percent of SEB-stimulated IL-6 secretion (217.53% ± 89.51%) was also significantly reduced following exposure to verapamil (148.82% ± 79.15%, p < 0.05) but not dexamethasone (148.86% ± 145.24%). Finally, the percent of SEB-stimulated thymic stromal lymphopoietin (TSLP) secretion (37.86% ± 18.88%) demonstrated a nonsignificant trend toward reduction with both dexamethasone (31.15% ± 35.28%) and verapamil (20.14% ± 12.10%).
Although the mechanism has yet to be fully understood, L-type CCBs are capable of reducing inflammation in multiple tissues. Verapamil was specifically found to reduce airway goblet cell hyperplasia and eosinophilic infiltration in a murine asthma model. Our data support these findings suggesting that verapamil can modulate T-helper cell type 2 (Th2)-associated cytokine secretion in sinonasal polyp explants. This data points to a possible therapeutic role for CCBs in the management of CRSwNP.
维拉帕米是一种 L 型钙通道阻滞剂（CCB），已在多种组织中显示出免疫调节特性。本研究的目的是确定维拉帕米是否能够调节鼻息肉中的细胞因子分泌，并将这种作用与地塞米松（一种已确立的免疫抑制皮质类固醇）进行比较。
这是一项机构审查委员会（IRB）批准的研究，涉及来自 8 名慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者的鼻息肉外植体。息肉用地塞米松或维拉帕米孵育 24 小时，然后再用葡萄球菌肠毒素 B（SEB）孵育 24 小时。通过酶联免疫吸附试验（ELISA）测定各暴露期分泌的细胞因子浓度，并表示为百分比。使用双尾学生 t 检验比较结果。
与第一治疗期相比，SEB 刺激的白细胞介素-5（IL-5）分泌的第二治疗期百分比（平均值±标准偏差[SD]，339.94%±315.48%））在接触地塞米松（74.08%±26.77%，p<0.05）和维拉帕米（119.99%±69.32%，p<0.05）后显著降低。SEB 刺激的白细胞介素-6（IL-6）分泌的百分比（217.53%±89.51%）也在接触维拉帕米后显著降低（148.82%±79.15%，p<0.05），但地塞米松没有（148.86%±145.24%）。最后，SEB 刺激胸腺基质淋巴生成素（TSLP）分泌的百分比（37.86%±18.88%）显示出与地塞米松（31.15%±35.28%）和维拉帕米（20.14%±12.10%）均呈降低趋势，但无统计学意义。
尽管其机制尚未完全阐明，但 L 型 CCB 能够减轻多种组织的炎症。维拉帕米已被发现可减少哮喘小鼠模型中的气道杯状细胞增生和嗜酸性粒细胞浸润。我们的数据支持这些发现，表明维拉帕米可以调节鼻息肉外植体中辅助性 T 细胞 2（Th2）相关细胞因子的分泌。这些数据表明 CCB 可能在治疗慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）方面具有潜在的治疗作用。
