title: Expression and relationship of proinflammatory chemokine RANTES/CCL5 and cytokine IL-1β in painful human intervertebral discs.
abstract: METHODS
  Laboratory study.
  
  
  OBJECTIVE
  To evaluate expression of chemokine regulated and normal T cell expressed and secreted (RANTES)/C-C motif ligand 5 (CCL5) and interleukins in intervertebral discs (IVDs) specimens from patients with discogram-proven painful degeneration.
  
  
  BACKGROUND
  Discogenic back pain results in tremendous costs related to treatment and lost productivity. The relationship between inflammation, degeneration (IVD), and cytokine upregulation is well established, but other mediators of the inflammatory cascade are not well characterized.
  
  
  METHODS
  Painful IVDs were taken from 18 patients undergoing surgery for discogenic pain with positive preoperative discogram. Painless control tissue was taken at autopsy from patients without back pain/spinal pathology or spinal levels with negative discograms resected for deformity.Quantitative real time polymerase chain reaction (qRT-PCR) was performed to evaluate RANTES, IL-1β, IL-6, and IL-8 expression in painful and control discs. RANTES and interleukin expression were analyzed on the basis of Pfirrmann grade.Disc cells were cultured in alginate beads using 2 groups: an untreated group and a group treated with 10 ng/mL IL-1β, 10 ng/mL TNF-α, and 1% fetal bovine serum to induce a degenerative phenotype.
  
  
  RESULTS
  Nine painless IVD specimens and 7 painful IVD specimens were collected. RANTES expression demonstrated a 3.60-fold increase in painful discs versus painless discs, a significant difference (P = 0.049). IL-1β expression demonstrated significantly higher expression in painful discs (P = 0.03). RANTES expression data demonstrated significant upregulation with increasing Pfirrmann grade (P = 0.045). RANTES expression correlated significantly with IL-1β expression (ρ = 0.67, P < 0.0001). RANTES expression increased more than 200-fold in the alginate culture model in cells treated with IL-1β/TNF-α, 1% fetal bovine serum (P < 0.001).
  
  
  CONCLUSIONS
  RANTES and IL-1β expression was significantly elevated in painful IVDs after careful selection of painless versus painful IVD tissue. RANTES expression was found to correlate significantly with expression of IL-1β. RANTES was upregulated by IL-1β/TNF-α/1% fetal bovine serum an in vitro treatment to induce a degenerative phenotype.
authors: Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA, USA. chris.kepler@gmail.com
authors: Christopher K
authors: CK
authors: Kepler
authors: Dessislava Z
authors: DZ
authors: Markova
authors: Florian
authors: F
authors: Dibra
authors: Sanjay
authors: S
authors: Yadla
authors: Alexander R
authors: AR
authors: Vaccaro
authors: Makarand V
authors: MV
authors: Risbud
authors: Todd J
authors: TJ
authors: Albert
authors: David Greg
authors: DG
authors: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics*; D015331:Cohort Studies; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D005312:Fetal Blood / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics* / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D008875:Middle Aged; D010146:Pain / Q000235:genetics / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018946:Chemokine CCL5; D003470:Culture Media; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha