Matsumori A, Ono K, Nishio R, Nose Y, Sasayama S
Department of Cardiovascular Medicine, Kyoto University, Japan.
Cytokine. 2000 Mar;12(3):294-7. doi: 10.1006/cyto.1999.0555.
Recent studies have suggested that cytokines are capable of modifying cardiovascular function and that drugs used in the treatment of heart failure have various modulating properties on the production of cytokines. More recently, we have found that ouabain induces the production of cytokines. This study was performed to examine the effects of calcium channel blockers on the production of cytokines induced by a cardiac glycoside. Human peripheral blood mononuclear cells (PBMC) were obtained from healthy volunteers. PBMC were cultured in 0.1, 1, 10, and 30 micromol/l amlodipine, diltiazem, and nifedipine in presence of 1 micromol/l ouabain. After 24 h of incubation, IL-1alpha, IL-1beta, IL-6, and TNF-alpha were measured in the culture supernatants by enzyme-linked immunosorbent assay. Ouabain induced the production of IL-1alpha, IL-1beta and IL-6, but not of TNF-alpha. Induction of IL-1beta was most prominent. The production of IL-1alpha, and IL-6 was inhibited by amlodipine in a concentration-dependent manner and was significantly decreased at a concentration of 10 micromol/l. IL-1beta production was also inhibited by 30 micromol/l amlodipine. In contrast, neither diltiazem nor nifedipine inhibited the production of these cytokines. The unique property of amlodipine to inhibit the production of IL-1alpha, IL-1beta and IL-6 may contribute to its beneficial effects in heart failure patients.
近期研究表明，细胞因子能够改变心血管功能，且用于治疗心力衰竭的药物对细胞因子的产生具有多种调节特性。最近，我们发现哇巴因可诱导细胞因子的产生。本研究旨在检测钙通道阻滞剂对强心苷诱导的细胞因子产生的影响。从健康志愿者获取人外周血单核细胞（PBMC）。将PBMC在含有1 μmol/L哇巴因的情况下，分别与0.1、1、10和30 μmol/L的氨氯地平、地尔硫䓬和硝苯地平一起培养。孵育24小时后，通过酶联免疫吸附测定法检测培养上清液中的IL-1α、IL-1β、IL-6和TNF-α。哇巴因诱导了IL-1α、IL-1β和IL-6的产生，但未诱导TNF-α的产生。IL-1β的诱导最为显著。氨氯地平以浓度依赖的方式抑制IL-1α和IL-6的产生，在浓度为10 μmol/L时显著降低。30 μmol/L的氨氯地平也抑制IL-1β的产生。相比之下，地尔硫䓬和硝苯地平均未抑制这些细胞因子的产生。氨氯地平抑制IL-1α、IL-1β和IL-6产生的独特特性可能有助于其对心力衰竭患者产生有益作用。
