title: Local application of interleukin-6 to the dorsal root ganglion induces tumor necrosis factor-α in the dorsal root ganglion and results in apoptosis of the dorsal root ganglion cells.
abstract: METHODS
  The mechanisms of apoptosis behind the formation of tissue reactions at the surface of the dorsal root ganglion (DRG) exposed to the nucleus pulposus were studied with special reference to the role of interleukin-6 (IL-6), using electron microscopy and immunohistochemistry in rats.
  
  
  OBJECTIVE
  To study the role of IL-6 on the DRG.
  
  
  BACKGROUND
  It has been reported that nucleus pulposus cells are capable to produce proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and IL-6. Recently, it was observed that local application of nucleus pulposus induced a characteristic tissue reaction at the surface of the DRG. This change was due to apoptosis of DRG neurons. However, the role of IL-6 is not known regarding the apoptosis of the DRG neurons.
  
  
  METHODS
  Recombinant IL-6 was applied between the L4 DRG and the dura to mimic a disc herniation of the L4-L5 disc in rats. The L4 DRGs were resected 24 hours after surgery. The sections were processed for immunohistochemistry using antisera to TNF-α. Furthermore, the sections of the specimens were observed using light and electron microscopy to confirm the induced apoptosis of the DRG neurons. The sections were also processed for immunohistochemistry, using antisera to single-stranded DNA (ssDNA) and Caspase 3.
  
  
  RESULTS
  TNF-α immunoreactivity was observed in the peripheral area of DRG at the site of the application of IL-6. Typical changes of the cell nuclei were observed in the DRG by light and electron microscopy, indicating the presence of apoptosis. The presence of ssDNA and Caspase 3 further enhanced the impression that there was apoptosis of the DRG neurons.
  
  
  CONCLUSIONS
  IL-6 seemed to induce TNF-α at the surface of DRG exposed to IL-6 and to induce a characteristic reaction at the surface of the DRG. IL-6 may thus play an important role in nucleus pulposus-induced apoptosis of the DRG neurons as well as TNF-α.
authors.affiliation: Department of Orthopaedic Surgery, Tokyo Women's Medical University, Tokyo, Japan. yasuakimurata@ort.twmu.ac.jp
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Murata
authors.forename: Björn
authors.initials: B
authors.lastname: Rydevik
authors.forename: Ulf
authors.initials: U
authors.lastname: Nannmark
authors.forename: Karin
authors.initials: K
authors.lastname: Larsson
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Kato
authors.forename: Kjell
authors.initials: K
authors.lastname: Olmarker
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000276:immunology / Q000502:physiology; D008159:Lumbar Vertebrae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha