Clinic of Cardiology, St Olavs Hospital Trondheim University Hospital, Trondheim, Norway
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
Open Heart. 2023 Aug;10(2). doi: 10.1136/openhrt-2023-002301.
Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size.
STEMI patients were randomised to receive a single dose of 280 mg tocilizumab (n=101) or placebo (n=98) before percutaneous coronary intervention. Blood samples were collected before infusion of tocilizumab or placebo at baseline, during follow-up at 24-36, 72-168 hours, 3 and 6 months. 27 cytokines were analysed using a multiplex cytokine assay. Cardiac MRI was performed during hospitalisation and 6 months.
Repeated measures analysis of variance showed significant (p<0.001) between-group difference in changes for IL-6, IL-8 and IL-1ra due to an increase in the tocilizumab group during hospitalisation. IL-6 and IL-8 correlated to neutrophils in the placebo group (r=0.73, 0.68, respectively), which was attenuated in the tocilizumab group (r=0.28, 0.27, respectively). A similar pattern was seen for MSI and IL-6 and IL-8 in the placebo group (r=-0.29, -0.25, respectively) in patients presenting ≤3 hours from symptom onset, which was attenuated in the tocilizumab group (r=-0.09,-0.14, respectively).
Tocilizumab increases IL-6, IL-8 and IL-1ra in STEMI. IL-6 and IL-8 show correlations to neutrophils/CRP and markers of cardiac injury in the placebo group that was attenuated in the tocilizumab group. This may suggest a beneficial effect of tocilizumab on the ischaemia-reperfusion injury in STEMI patients.
NCT03004703.
托珠单抗可改善 ST 段抬高型心肌梗死（STEMI）患者的心肌挽救指数（MSI），但其作用机制尚不清楚。在此，我们探讨了托珠单抗如何影响细胞因子，及其与中性粒细胞、C 反应蛋白（CRP）、肌钙蛋白 T、MSI 和梗死面积的相关性。
STEMI 患者在经皮冠状动脉介入治疗前随机接受单次 280mg 托珠单抗（n=101）或安慰剂（n=98）治疗。在托珠单抗或安慰剂输注前（基线）、输注后 24-36 小时、72-168 小时、3 个月和 6 个月时采集血液样本。采用多重细胞因子检测法分析 27 种细胞因子。住院期间和 6 个月时进行心脏 MRI。
重复测量方差分析显示，由于住院期间托珠单抗组的细胞因子水平升高，IL-6、IL-8 和 IL-1ra 存在有统计学意义的（p<0.001）组间差异。IL-6 和 IL-8 与安慰剂组中性粒细胞相关（r=0.73，0.68），而托珠单抗组的相关性减弱（r=0.28，0.27）。在症状发作 3 小时内就诊的患者中，MSI 与 IL-6 和 IL-8 之间也存在相似的关系（r=-0.29，-0.25），而托珠单抗组的相关性减弱（r=-0.09，-0.14）。
托珠单抗可增加 STEMI 患者的 IL-6、IL-8 和 IL-1ra。IL-6 和 IL-8 与中性粒细胞/CRP 和安慰剂组心脏损伤标志物相关，而托珠单抗组的相关性减弱。这可能表明托珠单抗对 STEMI 患者的缺血再灌注损伤具有有益作用。
NCT03004703。
