title: Human nucleus pulposis can respond to a pro-inflammatory stimulus.
abstract: METHODS
  Disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium analyzed for production of a range of pro-inflammatory mediators.
  
  
  OBJECTIVE
  This study was conducted to confirm that the human intervertebral disc is capable of responding to a pro-inflammatory stimulus and to identify the principal mediators involved in any response.
  
  
  BACKGROUND
  Degenerate human disc tissue has been shown to spontaneously secrete a number of pro-inflammatory mediators. The importance of these molecules in the pathophysiology of symptomatic disc degeneration is increasingly recognized. Human nucleus pulposus has been shown to synthesize increased amounts of interleukin (IL)-6, prostaglandin E2 (PGE2), and nitric oxide in response to stimulation with IL-1beta. Murine nucleus pulposus synthesizes increased amounts of IL-1beta, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor in response to lipopolysaccharide stimulation. Lipopolysaccharide is a potent inducer of tumor necrosis factor-alpha (TNF-alpha), which is thought to play an important role in the pathophysiology of sciatica. To date, human nucleus pulposus has not been shown to secrete TNF-alpha in response to a pro-inflammatory stimulus.
  
  
  METHODS
  Human disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium subsequently analyzed for a range of pro-inflammatory mediators.
  
  
  RESULTS
  None of the specimens produced any TNF-alpha, IL-1beta, granulocyte-macrophage colony-stimulating factor, or leukotriene B4. Measurable quantities of IL-6, IL-8, PGE2, MCP-1, basic fibroblast growth factor, and trans forming growth factor-beta1 were produced by a number of specimens. Lipopolysaccharide significantly increased IL-6, IL-8, and PGE2 production in both control and degenerate disc tissue. Degenerate disc specimens responded more vigorously to lipopolysaccharide stimulation than scoliotic specimens.
  
  
  CONCLUSIONS
  We conclude that both scoliotic and degenerate human nucleus pulposus can respond to an exogenous pro-inflammatory stimulus by secreting increased amounts of IL-6, IL-8, and PGE2 but not TNF-alpha and that degenerate disc tissue is more sensitive to a pro-inflammatory stimulus than its scoliotic counterpart.
authors.affiliation: Department of Orthopaedic Surgery and Surgical Professorial Unit, Mater Misericordiae Hospital Dublin and University College Dublin, Ireland. sean.deburca@virgin.net
authors.forename: J G
authors.initials: JG
authors.lastname: Burke
authors.forename: R W
authors.initials: RW
authors.lastname: G  Watson
authors.forename: D
authors.initials: D
authors.lastname: Conhyea
authors.forename: D
authors.initials: D
authors.lastname: McCormack
authors.forename: F E
authors.initials: FE
authors.lastname: Dowling
authors.forename: M G
authors.initials: MG
authors.lastname: Walsh
authors.forename: J M
authors.initials: JM
authors.lastname: Fitzpatrick
mesh_terms: D000293:Adolescent; D000328:Adult; D018932:Chemokine CCL2 / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D046508:Culture Techniques; D015232:Dinoprostone / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007403:Intervertebral Disc / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D013122:Spinal Diseases / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
chemical_list: D018932:Chemokine CCL2; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D015232:Dinoprostone