SYNOVIAL-MEMBRANE INFLAMMATION AND CYTOKINE PRODUCTION IN PATIENTS WITH EARLY OSTEOARTHRITIS

Objective. To establish the presence of inflammation in and cytokine p roduction by synovial membranes from patients with various stages of e arly 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 art hroscopy for unexplained knee pain or at the time of joint replacement surgery. Evaluations of synovial membrane variables including thickne ss of lining layer, vascularity, and inflammatory cell infiltrate were by a blinded observer. In a subset of 20 patients, production of inte rleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), tumor ne crosis factor alpha (TNF-alpha), and IL-1 receptor antagonist (IL-1ra) at the mRNA and protein levels was determined using in situ hybridiza tion with biotin labeled riboprobes and immunohistochemistry. Results. There was evidence of thickening of the lining layer increased vascul arity, and inflammatory cell infiltration in synovial membranes from p atients with all grades of OA, with the most marked changes seen in sy novial tissue from patients with advanced grades of OA. Similarly, pro duction of IL-1 alpha, IL-1 beta, and TNF-alpha was present in synovia l membranes from all patients with OA, irrespective of the degree of a rticular cartilage damage. There was a trend to decreased levels of IL -1ra in synovial membranes from patients with OA that did not attain s tatistical significance. Similarly, there was a decrease in the ratio of IL-1ra to IL-1 alpha and beta with increasing grades of OA, Conclus ion. Chronic inflammatory changes with production of proinflammatory c ytokines 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. Th is low grade synovitis results in the production of cytokines that may contribute to the pathogenesis of OA.