Beneficial effect of TNF-α inhibition on diabetic peripheral neuropathy

Yinghui Chen,Xiaohong Shi,Lubna Nadeem,Guoxiong Xu

doi:10.1186/1742-2094-10-69

Abstract

BackgroundTumor necrosis factor-α (TNF-α) is an important inflammatory factor produced by activated macrophages and monocytes and plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). To evaluate the effect of TNF-α signaling suppression and the potential of TNF-α in the treatment of DPN, a recombinant human TNF-α receptor-antibody fusion protein (rhTNFR:Fc) was used. We focused on the pathophysiology of the sciatic nerve and examined the expression of myelin basic protein (MBP) under DPN status with or without TNF-α inhibition.MethodsThe DPN rat model was generated by intraperitoneal injection of streptozotocin and by feeding with a high-fat, high-sugar diet. The nerve conduction velocity (NCV) in sciatic nerve of rat was monitored over a period of four weeks. The histopathological changes in nerve tissue were examined through traditional tissue histology and ultrastructure transmission electron microscopy (TEM). The expression of MBP was examined through western blot analysis.ResultsThe DPN induced rats showed significant signs of nerve damage including lower NCV, demyelination of nerve fibers, disorganization of lamellar and axonal structures, and decreased expression of MBP in the nerve tissue. The inhibition of TNF-α in the DPN rats resulted in a significant recovery from those symptoms compared to the DPN rats.ConclusionsOur study demonstrates that TNF-α plays a key role in the pathogenesis of DPN and its inhibition by rhTNFR:Fc can prove to be a useful therapeutic strategy for the treatment of and/or prevention from DPN symptoms.

Highlights

Tumor necrosis factor-α (TNF-α) is an important inflammatory factor produced by activated macrophages and monocytes and plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN)
Inhibition of TNF-α partially rescued the decrease of motor nerve conduction velocity and sensory nerve conduction velocity in diabetic peripheral neuropathy rat The DPN status is characterized by the lowering of MNCV and Sensory nerve conduction velocity (SNCV)
We found that animals with DPN had significantly lower MNCV and SNCV compared with control animals (Figure 1A and 1B; both P

Summary

Introduction

Tumor necrosis factor-α (TNF-α) is an important inflammatory factor produced by activated macrophages and monocytes and plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). We focused on the pathophysiology of the sciatic nerve and examined the expression of myelin basic protein (MBP) under DPN status with or without TNF-α inhibition. Diabetic peripheral neuropathy (DPN) is a severe longterm complication of diabetes affecting about 50% diabetic patients [1,2]. It is a condition associated with progressive degeneration of nerve fibers [3] and has become a growing concern of researchers and clinicians due to increased prevalence and vague etiology. The ultrastructure of the sciatic nerve and the expression of myelin basic protein (MBP) under DPN status with or without TNF-α inhibition were examined

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