Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study.
Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study.
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DOI：
10.1136/heartjnl-2013-303648
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Newby DE
中科院分区：
文献类型：
--
作者：
Padfield GJ;Din JN;Koushiappi E;Mills NL;Robinson SD;Cruden Nle M;Lucking AJ;Chia S;Harding SA;Newby DE
炎症细胞因子肿瘤坏死因子α (TNF-α)对心血管有有害影响。我们希望确定TNF-α拮抗剂对急性心肌梗死患者内皮功能和血小板活化的影响。在三级转诊心脏中心进行的双盲，平行组，随机对照试验。26例急性心肌梗死患者随机接受静脉输注依那西普（10mg）或生理盐水安慰剂。检测白细胞计数、血浆细胞因子浓度、血小板活化、外周血管舒缩和纤溶功能的流式细胞术测定。与有效结合循环TNF-α一致，依那西普后所有患者血浆TNF-α浓度均升高（254±15 vs 0.12±0.02 pg/ml; p<0.0001），但生理盐水输注无升高。依那西普在24小时降低中性粒细胞（7.4±0.6 vs 8.8±0.6×109细胞/l， p=0.03）和血浆白细胞介素-6浓度（5.8±2.0 vs 10.6±4.0 pg/ml, p=0.012），但增加血小板-单核细胞聚集（30±5 vs 20±3%,p=0.02）。两种治疗均未影响P物质、乙酰胆碱和硝普钠引起的血管舒张和急性组织型纤溶酶原激活剂释放（P < 0.01）。急性心肌梗死后，依那西普减少全身炎症，但增加血小板活化，而不影响外周血管舒缩或纤溶功能。我们得出结论，TNF-α拮抗剂不太可能是急性心肌梗死患者的有益治疗策略。
The inflammatory cytokine, tumour necrosis factor α (TNF-α), exerts deleterious cardiovascular effects. We wished to determine the effects of TNF-α antagonism on endothelial function and platelet activation in patients with acute myocardial infarction. A double-blind, parallel group, randomised controlled trial performed in a tertiary referral cardiac centre. 26 patients presenting with acute myocardial infarction randomised to receive an intravenous infusion of etanercept (10 mg) or saline placebo. Leucocyte count, plasma cytokine concentrations, flow cytometric measures of platelet activation and peripheral vasomotor and fibrinolytic function were determined before and 24 h after study intervention. Consistent with effective conjugation of circulating TNF-α, plasma TNF-α concentrations increased in all patients following etanercept (254±15 vs 0.12±0.02 pg/ml; p<0.0001), but not saline infusion. Etanercept treatment reduced neutrophil (7.4±0.6 vs 8.8±0.6×109 cells/l; p=0.03) and plasma interleukin-6 concentrations (5.8±2.0 vs 10.6±4.0 pg/ml; p=0.012) at 24 h but increased platelet–monocyte aggregation (30±5 vs 20±3%; p=0.02). Vasodilatation in response to substance P, acetylcholine and sodium nitroprusside, and acute tissue plasminogen activator release were unaffected by either treatment (p>0.1 for all). Following acute myocardial infarction, etanercept reduces systemic inflammation but increases platelet activation without affecting peripheral vasomotor or fibrinolytic function. We conclude that TNF-α antagonism is unlikely to be a beneficial therapeutic strategy in patients with acute myocardial infarction.
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