The Preventive Effect of IL-1beta Antagonist on Diabetic Peripheral Neuropathy

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Author(s): Zheng Hangping, Han Ling, Ji Lijin, Zhao Wenting, Liu Xiaoxia, Zhang Qi, Zhu Xiaoming, Li Qingchun, Li Yiming, Xiong Qian, Hu Ji, Lu Bin*, Zhang Shuo*.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

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Abstract:

Objective: To investigate the relationship between Interleukin-1beta (IL-1beta) and diabetic peripheral neuropathy (DPN) by clincial and animal findings.

Materials and Methods: Cross-sectional information was collected from 128 patients with type 2 diabetes mellitus. All of the participants were tested for DPN using Vibration Perception Threshold (VPT). We measured circulating levels of IL-1beta and interleukin-1 receptor antagonist (IL-1RA) by ELISA and assessed their associations with DPN, respectively. The rat model of diabetic neuropathy was induced by intraperitoneal injection of a single dose of STZ (65mg/kg). Diabetic animals were randomly divided into two groups (10 each), treated with 0.9% saline (DMS group) or IL-1RA (50mg/kg) (DMI group) respectively twice a day for 5 weeks. Ten normal rats matching with weight, age and sex served as normal control (Con group), treated with saline. Morphologic studies of sciatic nerves were examined by light and transmission electron microscopic techniques.

Results: Compared with individuals with normal VPT (≤15V), those with VPT values ≥25V or 16-24V both had a higher circulating levels of IL-1beta (p=0.004,or p=0.018,respectively) . After controlling for age, IL-1beta (r=0.262, p=0.031) and IL-RA (r=0.241, p=0.048) were both positively correlated with VPT. Among three rats groups(10 each), transmission electron microscopy of sciatic nerve showed the ultrastructure of myelin and axonal in IL-1RA group was highly protected compared to diabetic controls.

Conclusions: High circulating level of IL-1beta may be associated with the risk of DPN, anti-IL-1 treatment might be a potential strategy for prevention of diabetic neuropathy.

Keywords: Diabetic peripheral neuropathy, IL-1beta, IL-1RA, Inflammation, Prevention, Rats

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(E-pub Ahead of Print)
DOI: 10.2174/1871530319666191022114139
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