AMRINONE SUPPRESSES THE SYNTHESIS OF TUMOR-NECROSIS-FACTOR-ALPHA IN HUMAN MONONUCLEAR-CELLS
AMRINONE SUPPRESSES THE SYNTHESIS OF TUMOR-NECROSIS-FACTOR-ALPHA IN HUMAN MONONUCLEAR-CELLS
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DOI：
10.1097/00024382-199405000-00011
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发表时间：
1994-05-01
期刊：
影响因子：
3.1
通讯作者：
FULLE, HJ
中科院分区：
文献类型：
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作者：
ENDRES, S;SINHA, B;FULLE, HJ
肿瘤坏死因子-α（TNF）发挥广泛的生物活性，并有助于脓毒性休克的病理生理学。在重度慢性心力衰竭患者中也报告了TNF循环水平升高。我们研究了用于治疗急性心力衰竭的III类环核苷酸磷酸二酯酶抑制剂氨力农对体外TNF合成的影响。用细菌脂多糖和不同剂量的氨力农刺激来自健康志愿者的外周血单核细胞或永久性单核细胞系的细胞20小时。TNF的产生以剂量依赖的方式被抑制到1000 μ M的氨力农的最低9%的对照，在80 μ M的氨力农达到一半的最大抑制。这种作用似乎是通过cAMP介导的，在氨力农的存在下，cAMP积累了近两倍。通过治疗性施用磷酸二酯酶抑制剂如氨力农抑制TNF合成可能有助于其在心力衰竭治疗中的有益作用。
Tumor necrosis factor-alpha (TNF) exerts a wide spectrum of biological activities and contributes to the pathophysiology of septic shock. Elevated circulating levels of TNF have also been reported in patients with severe chronic heart failure. We studied the effect of amrinone, a class III cyclic nucleotide phosphodiesterase inhibitor used in the treatment of acute heart failure, on the synthesis of TNF in vitro. Peripheral blood mononuclear cells from healthy volunteers or cells of a permanent monoblast cell line were stimulated for 20 h with bacterial lipopolysaccharide and different doses of amrinone. TNF production is suppressed in a dose-dependent manner to a minimum of 9% of controls with 1000 muM of amrinone, reaching half-maximal inhibition at 80 muM amrinone. This effect appears to be mediated via cAMP, which accumulated nearly twofold in the presence of amrinone. Suppression of TNF synthesis by therapeutically administered phosphodiesterase inhibitors such as amrinone may contribute to their beneficial effect in the treatment of heart failure.