title: Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy.
abstract: OBJECTIVE
  To explore potential associations between proinflammatory cytokines in synovial fluid and progression of osteoarthritis (OA) in meniscectomized subjects.
  
  
  METHODS
  We studied 132 subjects on average 18 years after meniscectomy, with a second examination 4-10 years later. We measured concentrations of interleukin (IL)-6, -8 and tumor necrosis factor (TNF)-α by multiplex immunoassay, graded radiographic features of tibiofemoral and patellofemoral OA according to the Osteoarthritis Research Society International (OARSI) atlas, scored patient-reported outcomes using the Knee Injury and Osteoarthritis Outcome Score (KOOS), and used logistic regression (adjusted for age, gender, body mass index, and time between examinations) for assessment of associations.
  
  
  RESULTS
  Higher first examination concentrations of IL-6 and TNF-α were associated with increased risk for subsequent osteophyte progression (odds ratios (OR); 95% confidence intervals 1.05; 1.00-1.09 and 1.35; 1.03-1.75). Higher second examination concentrations of TNF-α were associated with having progressed in loss of joint space (OR 1.70; 1.15-2.52) or having worsened in the activity of daily living subscale of KOOS (OR 1.50; 1.07-2.09) in the preceding years. Subjects with increasing concentrations of IL-6 or TNF-α between examinations were five times more likely to have progressed in joint space narrowing between the same examinations, as compared to those with stable or decreasing concentrations (OR 5.17; 1.54-17.32 and 5.01; 1.32-18.92).
  
  
  CONCLUSIONS
  In subjects with previous meniscectomy, higher or over time increasing synovial fluid levels of IL-6 and TNF-α seems to be associated with increased risk for progression of radiographic OA.
authors.affiliation: Orthopaedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden. Electronic address: staffan.larsson@med.lu.se.
authors.forename: S
authors.initials: S
authors.lastname: Larsson
authors.affiliation: Orthopaedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Clinical Epidemiology Research & Training Unit, Boston University School of Medicine, Boston, MA, USA. Electronic address: martin.englund@med.lu.se.
authors.forename: M
authors.initials: M
authors.lastname: Englund
authors.affiliation: Orthopaedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden. Electronic address: andre.struglics@med.lu.se.
authors.forename: A
authors.initials: A
authors.lastname: Struglics
authors.affiliation: Orthopaedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; Research Unit for Musculoskeletal Function and Physiotherapy, University of Southern Denmark, Denmark; Department of Orthopaedics and Traumatology, University of Southern Denmark, Denmark. Electronic address: stefan.lohmander@med.lu.se.
authors.forename: L S
authors.initials: LS
authors.lastname: Lohmander
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007718:Knee Injuries / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008592:Menisci, Tibial / Q000601:surgery*; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism; D011184:Postoperative Period; D011379:Prognosis; D011859:Radiography; D012189:Retrospective Studies; D013582:Synovial Fluid / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Biomarkers; Cytokines; Meniscus injury; Osteoarthritis; Patient reported outcomes; Synovial fluid