The interleukin-6/interleukin-6-receptor system is activated in donor hearts

The interleukin-6/interleukin-6-receptor system is activated in donor hearts
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DOI:
10.1016/s0735-1097(02)01791-6
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发表时间:
2002-05-01
影响因子:
24
通讯作者:
Deng, MC
Deng, MC
中科院分区:
医学1区
文献类型:
--
作者:
Plenz, G;Eschert, H;Deng, MC

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为了评估供体心脏对白细胞介素-6(IL-6)应答的潜力,本研究调查了IL-6受体成分在供体心脏移植前心肌中的表达。背景供体心脏移植后早期功能障碍与供体脑死亡后的细胞因子风暴有关。促炎细胞因子被认为在这一过程中发挥核心作用。白细胞介素-6是特别感兴趣的,因为它与心脏移植物功能障碍有关,并与预后受损有关。其作用需要供体心脏中特异性IL 6受体(IL 6 R)和IL 6家族糖蛋白130(gp 130)的共同信号转导子的表达。通过逆转录-聚合酶链反应(RT-PCR)和免疫组织学研究供体心脏(n = 6)中IL 6 R和gp 130信使核糖核酸(mRNA)和蛋白质结果IL 6、IL 6 R和gp 130的mRNA表达明显高于正常对照组(P < 0. 05),且IL 6、IL 6 R和gp 130的mRNA表达明显高于正常对照组(P < 0. 05)。在供体心脏的所有腔室中表达,而对照患者的右心室没有显示任何表达(供体vs,对照:P < 0.005)。衰竭心脏的右心室显示IL 6、IL 6 R和gp 130 mRNA水平与供体心脏中发现的水平相当。免疫组化证实了RT-PCR数据的蛋白水平,而IL 6是主要由心肌细胞表达,这两种受体成分被优先发现主要在间质cells.CONCLUSIONS的表达的IL 6受体成分在供体心脏移植前建立的条件必要的非供心循环IL 6的反应。这一机制可能解释了围手术期早期血清IL 6水平升高与急性心脏移植物功能障碍的密切关系。(C)2002年,美国心脏病学会基金会。
OBJECTIVES To assess the potential of the donor heart to respond to interleukin-6 (IL6), the present study investigated the expression of IL6 receptor components in the myocardium of donor hearts before transplantation.BACKGROUND Donor heart dysfunction early, after transplantation has been associated with the cytokine storm after donor brain death. Proinflammatory cytokines are thought to play a central role in this process. Interleukin-6 is of specific interest because it has been associated with cardiac allograft dysfunction and is related to an impaired prognosis. Its action requires expression of the specific IL6 receptor (IL6R), and the common signal transducer of the IL6 family glycoprotein 130 (gp130) in the donor heart.METHODS The activation of IL6, IL6R and gp130 messenger ribonucleic acid (mRNA) and protein was studied via reverse transcription-polymerase chain reaction (RT-PCR) and immunohistology in donor hearts (n = 6) and compared with patients undergoing evaluation of ventricular arrhythmias (control, n = 9) or with advanced heart failure (n = 20).RESULTS Messenger RNA of IL6, IL6R and gp130 was strongly. expressed in all chambers of donor hearts, whereas right ventricles of control patients did not show any expression (donor vs, control: p < 0.005). Right ventricles of failing hearts showed IL6, IL6R and gp130 mRNA levels comparable with those found in donor hearts. Immunohistochemistry paralleled the RT-PCR data on the protein level, While IL6 was manily expressed by myocytes, both receptor components were preferentially found mainly on interstitial cells.CONCLUSIONS The expression of the IL6 receptor components in the donor heart before transplantation establishes the condition sine qua non for the response of the donor heart to circulating IL6. This mechanism may explain the close association of elevated IL6 serum levels to acute cardiac allograft dysfunction in the early perioperative period. (C) 2002 by the American College of Cardiology Foundation.