title: Synovial membrane inflammation and cytokine production in patients with early osteoarthritis.
abstract: OBJECTIVE
  To establish the presence of inflammation in and cytokine production by synovial membranes from patients with various stages of early osteoarthritis (OA), with knee pain, normal knee radiographs, and arthroscopic evidence of chondral damage.
  
  
  METHODS
  Synovial membrane samples were obtained from the knees of 63 patients at the time of arthroscopy for unexplained knee pain or at the time of joint replacement surgery. Evaluations of synovial membrane variables including thickness of lining layer, vascularity, and inflammatory cell infiltrate were by a blinded observer. In a subset of 20 patients, production of interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) at the mRNA and protein levels was determined using in situ hybridization with biotin labeled ribo-probes and immunohistochemistry.
  
  
  RESULTS
  There was evidence of thickening of the lining layer, increased vascularity, and inflammatory cell infiltration in synovial membranes from patients with all grades of OA, with the most marked changes seen in synovial tissue from patients with advanced grades of OA. Similarly, production of IL-1 alpha, IL-1 beta, and TNF-alpha was present in synovial membranes from all patients with OA, irrespective of the degree of articular cartilage damage. There was a trend to decreased levels of IL-1ra in synovial membranes from patients with OA that did not attain statistical significance. Similarly, there was a decrease in the ratio of IL-1ra to IL-1 alpha and beta with increasing grades of OA.
  
  
  CONCLUSIONS
  Chronic inflammatory changes with production of proinflammatory cytokines are a feature of synovial membranes from patients with early OA, with the most severe changes seen in patients at the time of joint replacement surgery resembling those seen in rheumatoid arthritis. This low grade synovitis results in the production of cytokines that may contribute to the pathogenesis of OA.
authors.affiliation: Department of Rheumatology, Repatriation General Hospital, Daw Park, Australia.
authors.forename: M D
authors.initials: MD
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Triantafillou
authors.forename: A
authors.initials: A
authors.lastname: Parker
authors.forename: P P
authors.initials: PP
authors.lastname: Youssef
authors.forename: M
authors.initials: M
authors.lastname: Coleman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001182:Arthroscopy; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053590:Interleukin 1 Receptor Antagonist Protein; D007719:Knee Joint / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012795:Sialoglycoproteins / Q000032:analysis / Q000096:biosynthesis; D013583:Synovial Membrane / Q000378:metabolism; D013585:Synovitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins