title: Enhanced integrative repair of the porcine meniscus in vitro by inhibition of interleukin-1 or tumor necrosis factor alpha.
abstract: OBJECTIVE
  To examine the hypotheses that increasing concentrations of interleukin-1 (IL-1) or tumor necrosis factor alpha (TNFalpha) inhibit the integrative repair of the knee meniscus in an in vitro model system, and that inhibitors of these cytokines will enhance repair.
  
  
  METHODS
  Explants (8 mm in diameter) were harvested from porcine medial menisci. To simulate a full-thickness defect, a 4-mm-diameter core was removed and reinserted. Explants were cultured for 14, 28, or 42 days in the presence of 0-1,000 pg/ml of IL-1 or TNFalpha. Explants were also cultured in the presence of IL-1 or TNFalpha with IL-1 receptor antagonist (IL-1Ra) or TNF monoclonal antibody (mAb). At the end of the culture period, biomechanical testing, cell viability, and histologic analyses were performed to quantify the extent of repair.
  
  
  RESULTS
  Mechanical testing revealed increased repair strength, cell accumulation, and tissue formation at the interface over time under control conditions. Pathophysiologic concentrations of both IL-1 and TNFalpha significantly decreased repair strength, cell migration, and tissue formation at the interface. The addition of IL-1Ra or TNF mAb to explants prevented the effects of IL-1 or TNFalpha, respectively.
  
  
  CONCLUSIONS
  Our findings document that physiologically relevant concentrations of IL-1 and TNFalpha inhibit meniscal repair in vitro and therefore may also inhibit meniscal repair during arthritis or following joint injury. The finding that IL-1Ra and TNF mAb promoted integrative meniscal repair in an inflammatory microenvironment suggests that intraarticular delivery of IL-1Ra and/or TNF mAb may be useful clinically to promote meniscal healing following injury.
authors.affiliation: Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: McNulty
authors.forename: Franklin T
authors.initials: FT
authors.lastname: Moutos
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.forename: Farshid
authors.initials: F
authors.lastname: Guilak
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D008592:Menisci, Tibial / Q000502:physiology*; D013552:Swine; D000070600:Tibial Meniscus Injuries; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha