OSTEOARTHRITIC SYNOVIAL-FLUID AND SYNOVIUM SUPERNATANTS UP-REGULATE TUMOR-NECROSIS-FACTOR RECEPTORS ON HUMAN ARTICULAR CHONDROCYTES

Objective: To determine whether the up-regulation of chondrocyte tumor necrosis factor receptor (TNF-R) expression in osteoarthritis (OA) is due to molecules released within the OA knee joint. Design: Non-arthr itic (NA) human articular chondrocytes were incubated with normal seru m, OA synovial fluid, or supernatants from either cultured NA or OA sy novium, and TNF-R expression measured by flow cytometry. Results: OA s ynovial fluid, but not normal serum, significantly up-regulated the pr oportion of chondrocytes expressing p55 TNF-R as well as the number of p55 TNF-R/chondrocyte. Similarly, supernatants from OA, but not NA, s ynovia significantly up-regulated chondrocyte p55 TNF-R expression. Ch ondrocyte p75 TNF-R expression was also significantly increased by som e of the OA supernatants but not others, and overall no significant in crease was seen. OA synovium supernatants contained higher concentrati ons of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) than NA synovium supernatants and neutralizing antibodies to these cytokines either partially or totally abrogated the ability of the OA supernatan ts to increase chondrocyte p55, TNF-R expression. Finally, various con centrations of recombinant human (rh)IL-1 beta and rhIL-6 up-regulated chondrocyte p55 TNF-R expression. Conclusion: These results suggest t hat IL-1 and IL-6 produced by OA synovium contribute to the progressio n of the disease by rendering chondrocytes more susceptible to stimula tion by catabolic cytokines.