Some recombinant human cytokines stimulate glycosaminoglycan synthesis in human synovial fibroblast cultures and inhibit it in human articular cartilage cultures

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Abstract
Recombinant human cytokines were compared for their effects on glycosaminoglycan (GAG) synthesis in human synovial fibroblast cultures and human articular cartilage explant cultures. In fibroblast cultures, recombinant human interleukin‐1α (rHuIL‐1α), rHuIL‐1β, and recombinant human tumor necrosis factor α (rHuTNFα) stimulated hyaluronic acid (HA) production and, to a lesser extent, sulfated GAG production, while recombinant human γ‐interferon did not have a significant effect. Half‐maximal stimulation of HA by rHuIL‐1β was 0.14 pM, while stimulation for rHuIL‐1α and rHuTNFα was 1.6 pM and 32 pM, respectively. Indomethacin (10 μg/ml) had no influence on HA stimulation by cytokines, while hydrocortisone (2–10 μg/ml) caused a significant reduction. In articular cartilage cultures, the cytokines inhibited production of sulfated GAGs. The activity of rHuIL‐1β was greater than that of rHuIL‐1α (half‐maximal inhibition at 0.71 pM and 4.7 pM, respectively) and both were considerably more active than rHuTNFα; γ‐interferon again had no significant effect. Neither indomethacin nor hydrocortisone influenced cytokine‐induced inhibition by either rHuIL‐1 preparation. These studies indicate that cytokines released during an inflammatory process may affect GAG synthesis in human joint tissues and may have opposite effects on GAG synthesis in different types of connective tissues.