Interleukin‐1‐induced interleukin‐6 is required for the inhibition of proteoglycan synthesis by interleukin‐1 in human articular cartilage

Cartilage from normal controls, patients with osteoarthritis, and patients with rheumatoid arthritis produced no interleukin‐6 (IL‐6) in culture. However, IL‐1 induced massive production of IL‐6 (up to 135 ng/ml) in cartilage from all 3 sources, in a dose‐dependent manner (in some cases, a peak value was reached). The levels of induced IL‐6 were similar to those found in rheumatoid arthritis synovial fluid. At IL‐1 concentrations that induced almost complete inhibition of proteoglycan (PG) synthesis, IL‐6 production could still be increased considerably. Exogenous IL‐6 inhibited PG synthesis by up to 25%. IL‐1‐induced inhibition of PG synthesis was reversed by antibodies against recombinant human IL‐6. These results suggest that IL‐6 is required for the IL‐1‐induced inhibition of PG synthesis.