title: Quantifying subtle but persistent peri-spine inflammation in vivo to submicron cobalt-chromium alloy particles.
abstract: OBJECTIVE
  We evaluated the consequences of cobalt-chromium alloy (CoCr) wear debris challenge in the peri-spine region to determine the inflammation and toxicity associated with submicron particulates of CoCr-alloy and nickel on the peri-spine.
  
  
  METHODS
  The lumbar epidural spaces of (n = 50) New Zealand white rabbits were challenged with: 2.5 mg CoCr, 5.0 mg CoCr, 10.0 mg CoCr, a positive control (20.0 mg of nickel) and a negative control (ISOVUE-M-300). The CoCr-alloy and Ni particles had a mean diameter of 0.2 and 0.6 μm, respectively. Five rabbits per dose group were studied at 12 and 24 weeks. Local and distant tissues were analyzed histologically and quantitatively analyzed immunohistochemically (TNF-α and IL-6).
  
  
  RESULTS
  Histologically, wear particles were observed in all animals. There was no evidence of toxicity or local irritation noted during macroscopic observations in any CoCr-dosed animals. However, Ni-treated control animals experienced bilateral hind leg paralysis and were euthanized at Day 2. Histopathology of the Ni particle-treated group revealed severe neuropathy. Quantitative immunohistochemistry demonstrated a CoCr-alloy dose-dependent increase in cytokines (IL-6, TNF-α, p < 0.05) at 12 and 24 weeks.
  
  
  CONCLUSIONS
  Subtle peri-spine inflammation associated with CoCr-alloy implant particles was dose dependent and persistent. Neuropathy can be induced by highly reactive Ni particles. This suggests peri-spine challenge with CoCr-alloy implant debris (e.g., TDA) is consistent with past reports using titanium alloy particles, i.e., mild persistent inflammation.
authors.affiliation: Department of Orthopaedic Surgery, Rush University Medical Center, 1735 West Harrison, Chicago, IL 60612, USA. nhallab@rush.edu
authors.forename: Nadim James
authors.initials: NJ
authors.lastname: Hallab
authors.forename: Frank W
authors.initials: FW
authors.lastname: Chan
authors.forename: Megan L
authors.initials: ML
authors.lastname: Harper
mesh_terms: D000818:Animals; D002858:Chromium Alloys / Q000009:adverse effects*; D016207:Cytokines / Q000032:analysis; D004824:Epidural Space / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D008161:Lumbosacral Region; D008297:Male; D011817:Rabbits; D013122:Spinal Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology
chemical_list: D002858:Chromium Alloys; D016207:Cytokines