Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Atherosclerosis. 2013 Jul;229(1):174-81. doi: 10.1016/j.atherosclerosis.2013.04.031. Epub 2013 May 11.
Blocking the interleukin-6 pathway by tocilizumab (TCZ) has been associated with changes in the lipoprotein profile, which could adversely impact cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). In the present study, we addressed the effect of TCZ on lipoproteins in both fasting and non-fasting state in RA patients and tested the effect of TCZ on LDL receptor (LDLr) expression in vitro.
Twenty patients with active RA and an inadequate response to TNF blockers received monthly TCZ intravenously. On week 0, 1 and 6 blood was drawn before and after an oral fat load, the lipid profiles and HDL antioxidative capacity were measured. Effects of TCZ on LDLr expression in transfected HepG2 cells were subjected.
After 6 weeks of TCZ, total cholesterol increased by 22% (4.8 ± 0.9 to 5.9 ± 1.3 mmol/L; p < 0.001), LDLc by 22% (3.0 ± 0.6 to 3.6 ± 0.8 mmol/L; p < 0.001) and HDLc by 17% (1.4 ± 0.4 to 1.7 ± 0.7 mmol/L; p < 0.016). Fasting triglycerides (TG) increased by 48% (1.0 ± 0.4 to 1.4 ± 0.8 mmol/L; p = 0.011), whereas postprandial incremental area under the curve TG increased by 62% (p = 0.002). Lipid changes were unrelated to the change in disease activity or inflammatory markers. No difference in HDL antioxidative capacity was found. In vitro, LDLr expression in cultured liver cells was significantly decreased following TCZ incubation (P < 0.001).
TCZ adversely impacts on both LDLc as well as fasting and postprandial TG in patients with RA. The changes in hepatic LDLr expression following TCZ imply that adverse lipid changes may be a direct hepatic effect of TCZ. The net effect of TCZ on CV-morbidity has to be confirmed in future clinical trials.
通过托珠单抗（TCZ）阻断白细胞介素-6 通路与脂蛋白谱的变化有关，这可能会对类风湿关节炎（RA）患者的心血管（CV）风险产生不利影响。在本研究中，我们研究了 TCZ 在 RA 患者空腹和非空腹状态下对脂蛋白的影响，并检测了 TCZ 对 LDL 受体（LDLr）表达的体外影响。
20 例对 TNF 阻滞剂反应不足的活动期 RA 患者每月接受一次 TCZ 静脉注射。在第 0、1 和 6 周，在口服脂肪负荷前后抽取血液，测量血脂谱和 HDL 抗氧化能力。检测 TCZ 对转染 HepG2 细胞中 LDLr 表达的影响。
TCZ 治疗 6 周后，总胆固醇增加 22%（4.8±0.9 至 5.9±1.3mmol/L；p<0.001），LDLc 增加 22%（3.0±0.6 至 3.6±0.8mmol/L；p<0.001），HDLc 增加 17%（1.4±0.4 至 1.7±0.7mmol/L；p<0.016）。空腹甘油三酯（TG）增加 48%（1.0±0.4 至 1.4±0.8mmol/L；p=0.011），而餐后 TG 曲线下面积增加 62%（p=0.002）。血脂变化与疾病活动度或炎症标志物的变化无关。HDL 抗氧化能力无差异。体外培养肝细胞 LDLr 表达明显降低（P<0.001）。
TCZ 可导致 RA 患者 LDLc 以及空腹和餐后 TG 水平不良。TCZ 后肝 LDLr 表达的变化表明，不良的血脂变化可能是 TCZ 的直接肝作用。TCZ 对 CV 发病率的净效应还需要在未来的临床试验中证实。
