Huang Lei, Liu Shaojiang, Song Tao, Zhang Wentao, Fan Jinzhu, Liu Yang
Southern Medical University, Nanfang Hospital, Department of Burn, Guangzhou, Guangdong, 510515, China.
Biochemistry (Mosc). 2017 Oct;82(10):1193-1199. doi: 10.1134/S0006297917100121.
Level of interleukin 6 (IL-6) is associated with fracture healing. This study was performed to explore the effect of IL-6 blockade on fracture healing. Clinical serum levels of IL-6 and tumor necrosis factor-α (TNF-α) were evaluated by enzyme-linked immunosorbent assay (ELISA). For animal experiments, the IL-6 levels after fracture and treatment with rat anti-mouse IL-6 receptor antibody (MR16-1) were assessed. Then, mice were assigned into four or seven groups: control group, fracture group, isotype IgG group, and MR16-1 groups. Serum levels of IL-6 and TNF-α, relative flexural rigidity, and mRNA levels of osteoblast-specific genes were respectively assayed by ELISA, three-point bending test, and quantitative reverse transcription PCR (qRT-PCR). Serum levels of IL-6 and TNF-α after fracture in humans and mice were increased. The increase in IL-6 and TNF-α levels in murine serum was attenuated by MR16-1 treatment. The three-point bending test showed the relative flexural rigidity of the femur was decreased after fracture, whereas the decrease was alleviated by MR16-1 treatment. The qRT-PCR results demonstrated mRNA levels of osteoblast-specific genes were upregulated after fracture and then further upregulated by MR16-1 treatment in a dose-dependent manner. Collectively, the serum level of IL-6 was elevated after fracture both in clinical and murine samples. IL-6 blockade by MR16-1 promoted fracture healing, which might be associated with changes in expression of osteoblast-specific genes.
白细胞介素6（IL-6）水平与骨折愈合相关。本研究旨在探讨IL-6阻断对骨折愈合的影响。采用酶联免疫吸附测定（ELISA）评估临床血清中IL-6和肿瘤坏死因子-α（TNF-α）水平。对于动物实验，评估骨折后及用大鼠抗小鼠IL-6受体抗体（MR16-1）治疗后的IL-6水平。然后，将小鼠分为四组或七组：对照组、骨折组、同型IgG组和MR16-1组。分别通过ELISA、三点弯曲试验和定量逆转录PCR（qRT-PCR）检测血清中IL-6和TNF-α水平、相对抗弯刚度以及成骨细胞特异性基因的mRNA水平。人类和小鼠骨折后的血清IL-6和TNF-α水平均升高。MR16-1治疗可减轻小鼠血清中IL-6和TNF-α水平的升高。三点弯曲试验显示，骨折后股骨的相对抗弯刚度降低，而MR16-1治疗可减轻这种降低。qRT-PCR结果表明，骨折后成骨细胞特异性基因的mRNA水平上调，随后MR16-1治疗以剂量依赖方式进一步上调。总体而言，临床和小鼠样本骨折后血清IL-6水平均升高。MR16-1阻断IL-6可促进骨折愈合，这可能与成骨细胞特异性基因表达的变化有关。
