title: Associations between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee.
abstract: BACKGROUND
  One of the sources of knee pain in osteoarthritis (OA) is believed to be related to local chronic inflammation of the knee joints, which involves the production of inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin (IL)-6, and nerve growth factor (NGF) in the synovial membrane, and these cytokines are believed to promote pathological OA. In the present study, correlations between proinflammatory cytokines in knee synovial fluid and radiographic changes and functional scores and pain scores among OA patients were examined.
  
  
  METHODS
  Synovial fluid was harvested from the knees of 47 consecutive OA patients, and the levels of TNFα, IL-6, and NGF were measured using enzyme-linked immunosorbent assays. Osteoarthritic knees were classified using Kellgren-Lawrence (KL) grading (1-4). The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness.
  
  
  RESULTS
  TNFα and IL-6 were detectable in knee synovial, whereas NGF was not. TNFα was not correlated with the KL grade, whereas IL-6 had a significantly negative correlation. We observed differences in the correlations between TNFα and IL-6 with WOMAC scores and their subscales (pain, stiffness, and physical function). TNFα exhibited a significant correlation with the total score and its 3 subscales, whereas IL-6 exhibited a moderately significant negative correlation only with the subscale of stiffness.
  
  
  CONCLUSIONS
  The present study demonstrated that the concentrations of proinflammatory cytokines are correlated with KL grades and WOMAC scores in patients with knee OA. Although TNFα did not have a significant correlation with the radiographic grading, it was significantly associated with the WOMAC score. IL-6 had a significant negative correlation with the KL grading, whereas it had only a weakly significant correlation with the subscore of stiffness. The results suggest that these cytokines play a role in the pathogenesis of synovitis in osteoarthritic knees in different ways: TNFα is correlated with pain, whereas IL-6 is correlated with joint function.
authors.affiliation: Department of Orthopaedic Surgery, Chiba Rosai Hospital, Chiba, Japan. sumihisa@silver.email.ne.jp
authors.forename: Sumihisa
authors.initials: S
authors.lastname: Orita
authors.forename: Takana
authors.initials: T
authors.lastname: Koshi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mitsuka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyagi
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.forename: Gen
authors.initials: G
authors.lastname: Arai
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Hanaoka
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Masaomi
authors.initials: M
authors.lastname: Yamashita
authors.forename: Yawara
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Toyone
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohtori
mesh_terms: D000368:Aged; D018771:Arthralgia / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D001175:Arthrography / Q000379:methods; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000009:adverse effects* / Q000502:physiology; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000502:physiology; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000378:metabolism* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects* / Q000502:physiology
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D020932:Nerve Growth Factor