Blockade of Interleukin 6 by Rat Anti-mouse Interleukin 6 Receptor Antibody Promotes Fracture Healing

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Lei Huang^1#, Shaojiang Liu^2#, Tao Song³, Wentao Zhang³, Jinzhu Fan³, and Yang Liu^3*

¹Southern Medical University, Nanfang Hospital, Department of Burn, Guangzhou 510515, Guangdong, China

²Panzhihua Central Hospital, Department of Orthopaedics, Panzhihua 617067, Sichuan, China

³Department of Orthopaedics, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi, China; E-mail: liuyang152@126.com

^# These authors contributed equally to this work.

^* To whom correspondence should be addressed.

Received February 10, 2017; Revision received August 25, 2017

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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.

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KEY WORDS: type II procollagen, type X procollagen, receptors, interleukin 6, tumor necrosis factor-α

DOI: 10.1134/S0006297917100121

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