title: Attenuation of inflammatory events in human intervertebral disc cells with a tumor necrosis factor antagonist.
abstract: METHODS
  The inflammatory responses of primary human intervertebral disc (IVD) cells to tumor necrosis factor α (TNF-α) and an antagonist were evaluated in vitro.
  
  
  OBJECTIVE
  To investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize TNF-α-induced inflammatory events in primary human IVD cells in vitro.
  
  
  BACKGROUND
  TNF-α is a known mediator of inflammation and pain associated with radiculopathy and IVD degeneration. sTNFRs and their analogues are of interest for the clinical treatment of these IVD pathologies, although information on the effects of sTNFR on human IVD cells remains unknown.
  
  
  METHODS
  IVD cells were isolated from surgical tissues procured from 15 patients and cultured with or without 1.4 nmol/L TNF-α (25 ng/mL). Treatment groups were coincubated with varying doses of sTNFRII (12.5-100 nmol/L). Nitric oxide (NO), prostaglandin E₂ (PGE₂), and interleukin-6 (IL6) levels in media were quantified to characterize the inflammatory phenotype of the IVD cells.
  
  
  RESULTS
  Across all patients, TNF-α induced large, statistically significant increases in NO, PGE₂, and IL6 secretion from IVD cells compared with controls (60-, 112-, and 4-fold increases, respectively; P < 0.0001). Coincubation of TNF-α with nanomolar doses of sTNFRII significantly attenuated the secretion of NO and PGE₂ in a dose-dependent manner, whereas IL6 levels were unchanged. Mean IC₅₀ values for NO and PGE₂ were found to be 35.1 and 20.5 nmol/L, respectively.
  
  
  CONCLUSIONS
  Nanomolar concentrations of sTNFRII were able to significantly attenuate the effects of TNF-α on primary human IVD cells in vitro. These results suggest this sTNFR to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: S Michael
authors.initials: SM
authors.lastname: Sinclair
authors.forename: Mohammed F
authors.initials: MF
authors.lastname: Shamji
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Liufang
authors.initials: L
authors.lastname: Jing
authors.forename: William J
authors.initials: WJ
authors.lastname: Richardson
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Brown
authors.forename: Robert D
authors.initials: RD
authors.lastname: Fitch
authors.forename: Lori A
authors.initials: LA
authors.lastname: Setton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D015232:Dinoprostone