Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan.
Circ J. 2010 Mar;74(3):567-71. doi: 10.1253/circj.cj-09-0467. Epub 2010 Jan 30.
Calcium channel blockers (CCB) are known to modulate immune reactions, so the present study was performed to examine the effects of various CCBs that have shown different effects on transcription factors and on the production of pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMC).
PBMC from healthy volunteers were isolated by Ficoll-paque density centrifugation. To study the effect of CCBs, the PBMC were stimulated with lipopolysaccharide or concanavalin A. After 24 h of incubation, the supernatants were harvested and the interleukin (IL)-1alpha, -1beta, and -6, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma levels were determined by specific enzyme-linked immunosorbent assay. The production of IL-1alpha and -1beta stimulated with lipopolysaccharide was significantly increased in the presence of amlodipine. In contrast, nifedipine and verapamil suppressed the production of IL-1beta, TNF-alpha, and IFN-gamma. Amlodipine and diltiazem significantly increased production of IL-1alpha stimulated with concanavalin A. Nifedipine inhibited production of IL-1alpha, IL-6, and IFN-gamma. Verapamil suppressed production of IFN-gamma.
Differential modulation of cytokine production was seen with various CCBs, and the suppressive effect of nifedipine was most prominent.
钙通道阻滞剂 (CCB) 已知可调节免疫反应，因此本研究旨在检查各种 CCB 的作用，这些 CCB 对转录因子具有不同的作用，并对人外周血单核细胞 (PBMC) 产生促炎细胞因子的作用。
通过 Ficoll-paque 密度离心从健康志愿者中分离 PBMC。为了研究 CCB 的作用，用脂多糖或刀豆蛋白 A 刺激 PBMC。孵育 24 小时后，收获上清液，并通过特异性酶联免疫吸附试验测定白细胞介素 (IL)-1alpha、-1beta 和 -6、肿瘤坏死因子 (TNF)-alpha 和干扰素 (IFN)-gamma 的水平。脂多糖刺激的 IL-1alpha 和 -1beta 的产生在用氨氯地平存在下显著增加。相比之下，硝苯地平和维拉帕米抑制了 IL-1beta、TNF-alpha 和 IFN-gamma 的产生。氨氯地平和地尔硫卓显著增加了刀豆蛋白 A 刺激的 IL-1alpha 的产生。硝苯地平抑制了 IL-1alpha、IL-6 和 IFN-gamma 的产生。维拉帕米抑制 IFN-gamma 的产生。
各种 CCB 对细胞因子产生的调节作用存在差异，硝苯地平的抑制作用最为显著。
