title: Beneficial effect of TNF-α inhibition on diabetic peripheral neuropathy.
abstract: BACKGROUND
  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). 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Endocrinology, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Shi
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Chen
authors.forename: Lubna
authors.initials: L
authors.lastname: Nadeem
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009046:Motor Neurons / Q000187:drug effects; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009412:Nerve Fibers / Q000473:pathology; D009431:Neural Conduction / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012584:Sciatic Nerve / Q000473:pathology / Q000648:ultrastructure; D011984:Sensory Receptor Cells / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D004676:Myelin Basic Protein; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha