Myers P R, Parker J L, Tanner M A, Adams H R
Department of Medicine, College of Medicine, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, Missouri, USA.
Shock. 1994 Jan;1(1):73-8. doi: 10.1097/00024382-199401000-00013.
Endotoxemia results in the release of cytokines that exert complex effects on the cardiovascular system. The purpose of this study was to 1) determine if interleukin 1 beta (IL1 beta) and tumor necrosis factor alpha (TNF alpha) elicit the release of endothelium-derived relaxing factor (EDRF) and nitric oxide derived from the constitutive nitric oxide synthase present in vascular endothelium, and 2) determine if these cytokines alter endotoxin-mediated decreases in EDRF bioactivity and nitric oxide production. Cultured bovine aortic endothelial cells were directly exposed to endotoxin, human recombinant TNF alpha, interleukin 1 beta, or a combination of endotoxin and cytokine for 1 h, followed by a second hour without endotoxin. Subsequently, both basal as well as agonist-stimulated (bradykinin) EDRF bioactivity and nitric oxide (NO) content of the effluent were quantitated. In additional experiments, endothelial cells were exposed acutely over a 30-min assay period to either endotoxin alone, cytokine alone, or endotoxin and cytokine. Following the 2-h incubation, endotoxin alone markedly reduced basal EDRF bioactivity and NO production (44 +/- 13% control, 66 +/- 13% control, respectively) and decreased bradykinin-stimulated EDRF bioactivity and NO production (58 +/- 5% control, 55 +/- 4% control, respectively). TNF alpha and IL1 beta did not stimulate EDRF release or NO production either acutely or after prolonged exposure, nor did they alter agonist-stimulated EDRF bioactivity and NO production. Similarly co-incubation of endotoxin with TNF alpha or IL1 beta failed to significantly alter the inhibitory effects of endotoxin on EDRF bioactivity and NO production.(ABSTRACT TRUNCATED AT 250 WORDS)
内毒素血症会导致细胞因子释放，这些细胞因子会对心血管系统产生复杂影响。本研究的目的是：1）确定白细胞介素1β（IL1β）和肿瘤坏死因子α（TNFα）是否会引发血管内皮中组成型一氧化氮合酶产生的内皮源性舒张因子（EDRF）和一氧化氮的释放；2）确定这些细胞因子是否会改变内毒素介导的EDRF生物活性降低和一氧化氮生成减少。将培养的牛主动脉内皮细胞直接暴露于内毒素、人重组TNFα、白细胞介素1β或内毒素与细胞因子的组合中1小时，随后1小时不接触内毒素。随后，对流出物的基础以及激动剂刺激（缓激肽）的EDRF生物活性和一氧化氮（NO）含量进行定量。在另外的实验中，在30分钟的检测期内将内皮细胞急性暴露于单独的内毒素、单独的细胞因子或内毒素与细胞因子中。经过2小时的孵育后，单独的内毒素显著降低基础EDRF生物活性和NO生成（分别为对照的44±13%、66±13%），并降低缓激肽刺激的EDRF生物活性和NO生成（分别为对照的58±5%、55±4%）。TNFα和IL1β无论是急性暴露还是长时间暴露后都不会刺激EDRF释放或NO生成，它们也不会改变激动剂刺激的EDRF生物活性和NO生成。同样，内毒素与TNFα或IL1β共同孵育也未能显著改变内毒素对EDRF生物活性和NO生成的抑制作用。（摘要截短于250字）
