Newman W H, Castresana M R, Webb J G, Wang Z, Warejcka D J
Department of Anesthesiology, Mercer University School of Medicine and Medical Center of Central Georgia, Macon, USA.
Crit Care Med. 2000 Nov;28(11):3593-8. doi: 10.1097/00003246-200011000-00004.
Beta-adrenergic receptor agonists such as isoproterenol inhibit production of tumor necrosis factor (TNF)-alpha in a number of cell types. Because the heart is a source of TNF-alpha, we hypothesized that isoproterenol would inhibit cardiac production of the cytokine.
Analysis of cardiac release of TNF-alpha.
Medical research laboratory.
Rats.
None.
With the approval of the Institutional Animal Care and Use Committee, rats were anesthetized and hearts were removed and perfused. After 30 mins, bacterial lipopolysaccharide (LPS) with or without isoproterenol was infused for 60 mins. At 30, 60, 90, 120, and 150 mins, coronary flow was measured and coronary effluent was analyzed for TNF-alpha. Cardiac production of TNF-alpha was expressed as pg/min. Cyclic adenosine monophosphate (AMP) in the coronary effluent was measured. TNF-alpha messenger RNA was determined in ventricular tissue. After 30 mins, TNF-alpha was undetectable in the coronary effluent However, 60 mins after the initiation of LPS infusion, TNF-alpha release was 875+/-255 pg/min and increased to 2164+/-721 pg/min at 150 mins. Simultaneous infusion of isoproterenol with LPS stimulated cyclic AMP release and inhibited TNF-alpha production. For instance, at 60 and 150 mins, TNF-alpha release was 75+/-38 and 58+/-29 pg/min, respectively (p < .05 vs. LPS alone). Simultaneous infusion of isoproterenol with LPS blocked the induction of TNF-alpha messenger RNA by LPS. Isoproterenol, begun 30 mins after the initiation of LPS infusion, still suppressed LPS-stimulated TNF-alpha release by 95% at 150 mins. Similar results were obtained with norepinephrine.
Activation of beta-adrenergic receptors inhibits cardiac TNF-alpha release. This implies that cytokine production by the heart is inhibited by the sympathetic nervous system. In heart failure, the cardiac response to the sympathetic nervous system is impaired. This impairment may play a role in the high plasma levels of TNF-alpha found in heart failure.
β-肾上腺素能受体激动剂如异丙肾上腺素可抑制多种细胞类型中肿瘤坏死因子（TNF）-α的产生。由于心脏是TNF-α的来源之一，我们推测异丙肾上腺素会抑制心脏中细胞因子的产生。
分析心脏中TNF-α的释放情况。
医学研究实验室。
大鼠。
无。
经机构动物护理和使用委员会批准，将大鼠麻醉后取出心脏并进行灌注。30分钟后，分别灌注含或不含异丙肾上腺素的细菌脂多糖（LPS）60分钟。在30、60、90、120和150分钟时，测量冠状动脉血流量，并分析冠状动脉流出液中的TNF-α。心脏中TNF-α的产生量以pg/分钟表示。测量冠状动脉流出液中的环磷酸腺苷（AMP）。测定心室组织中的TNF-α信使核糖核酸。30分钟后，冠状动脉流出液中未检测到TNF-α。然而，在开始注入LPS 60分钟后，TNF-α释放量为875±255 pg/分钟，在150分钟时增加到2164±721 pg/分钟。异丙肾上腺素与LPS同时注入可刺激环AMP释放并抑制TNF-α的产生。例如，在60和150分钟时，TNF-α释放量分别为75±38和58±29 pg/分钟（与单独使用LPS相比，p<.05）。异丙肾上腺素与LPS同时注入可阻断LPS对TNF-α信使核糖核酸的诱导。在开始注入LPS 30分钟后开始注入异丙肾上腺素，在150分钟时仍可将LPS刺激的TNF-α释放抑制95%。去甲肾上腺素也得到了类似的结果。
β-肾上腺素能受体的激活可抑制心脏TNF-α的释放。这意味着心脏中细胞因子的产生受到交感神经系统的抑制。在心力衰竭中，心脏对交感神经系统的反应受损。这种损害可能在心力衰竭患者血浆中高水平的TNF-α中起作用。
