INDUCTION OF INTERLEUKIN-6 SYNTHESIS IN THE MYOCARDIUM - POTENTIAL ROLE IN POSTREPERFUSION INFLAMMATORY INJURY
INDUCTION OF INTERLEUKIN-6 SYNTHESIS IN THE MYOCARDIUM - POTENTIAL ROLE IN POSTREPERFUSION INFLAMMATORY INJURY
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DOI：
10.1161/01.cir.92.7.1866
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发表时间：
1995-10-01
期刊：
影响因子：
37.8
通讯作者：
ENTMAN, ML
中科院分区：
文献类型：
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作者：
KUKIELKA, GL;SMITH, CW;ENTMAN, ML
中性粒细胞诱导的心肌细胞损伤需要在心肌细胞表面表达细胞间粘附分子-1 (ICAM-1)，并通过ICAM-1- cd11b /CD18粘附介导。我们之前已经证明，存在于心脏淋巴中的白细胞介素-6 （IL-6）细胞因子活性可诱导离体心肌细胞上的ICAM-1。此外，在之前的体内研究中，我们也发现了ICAM-1 mRNA在缺血活区再灌注后的第一个小时内在心肌中的诱导作用。我们假设心肌中IL-6合成的诱导是缺血再灌注损伤反应的一个组成部分，并与心肌细胞上ICAM-1的诱导有关。方法与结果本研究以克隆犬IL-6 cDNA为分子探针，研究IL-6在清醒犬心肌缺血再灌注模型中的调控作用。IL-6 mRNA在心肌缺血和再灌注段中被诱导，优先在先前暴露于严重缺血的段中。IL-6 mRNA水平在再灌注3小时内达到峰值。同时在同一心肌节段中检测到IL-6 mRNA和ICAM-1 mRNA。与缺血1小时再灌注3小时的心脏相比，持续缺血4小时后未再灌注的心脏，尽管缺血期间损伤程度和血流量减少相似，但ICAM-1或IL-6的诱导程度最小。持续缺血24小时后，IL-6 mRNA水平与缺血1小时后再灌注24小时的心脏中观察到的水平相当。结论IL-6 mRNA在心肌中的表达受到诱导，再灌注可加速其合成。也有证据表明IL-6 mRNA的峰值先于ICAM-1 mRNA的峰值。这些发现与我们的假设一致，即IL-6在缺血区域诱导ICAM-1中起重要作用。此外，这些研究表明，促进迁移中性粒细胞与心肌细胞之间黏附相互作用的必要因素存在于再灌注心肌中。
Background Neutrophil-induced injury of myocardial cells requires the expression of intercellular adhesion molecule-1 (ICAM-1) on the myocyte surface and is mediated by ICAM-1-CD11b/CD18 adhesion. We have previously shown that interleukin-6 (IL-6) cytokine activity, present in cardiac lymph, induces ICAM-1 on isolated cardiac myocytes. Furthermore, in previous in vivo studies, we have also shown ICAM-1 mRNA induction in the myocardium within the first hour of reperfusion in the previously ischemic viable zone. We hypothesized that induction of IL-6 synthesis in the myocardium was an integral part of the reaction to injury resulting from ischemia and reperfusion and was associated with induction of ICAM-1 on myocardial cells.Methods and Results In this study, cloned canine IL-6 cDNA was used as a molecular probe to study the regulation of IL-6 in an awake canine model of myocardial ischemia and reperfusion. IL-6 mRNA was induced in ischemic and reperfused segments of myocardium preferentially in segments previously exposed to severe ischemia. Peak levels of IL-6 mRNA were reached within 3 hours of reperfusion. At the same time, IL-6 mRNA and ICAM-1 mRNA were found in the same myocardial segments. In contrast to hearts that were ischemic for 1 hour and reperfused for 3 hours, nonreperfused hearts after 4 hours of persistent ischemia demonstrated minimal induction of ICAM-1 or IL-6 despite similar degrees of injury and blood flow reductions during ischemia. After 24 hours of persistent ischemia, levels of IL-6 mRNA were comparable to those observed in hearts that were ischemic for 1 hour and subsequently reperfused for 24 hours.Conclusions Our results demonstrate induction of IL-6 mRNA in the myocardium and that this synthesis is accelerated by reperfusion. Evidence is also provided to show that peak IL-6 mRNA precedes that of ICAM-1 mRNA. These findings are compatible with our hypothesis that IL-6 is important in the induction of ICAM-1 in the area of ischemia. In addition, these studies suggest that the necessary factors to promote adhesive interactions between transmigrated neutrophils and cardiac myocytes are present in reperfused myocardium.