Effect of purified human interleukin‐1 on cartilage degradation

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Abstract
The effects of highly purified human monocyte‐derived interleukin‐1 (IL‐1) on bovine nasal cartilage breakdown were investigated. Cartilage degradation was determined by quantifying the fraction of total proteoglycan released from cartilage during 8 days of culture. The response appeared to be chondrocyte‐dependent, for IL‐1 stimulated proteoglycan (PG) release from living but not from dead (frozen‐thawed) cartilage. IL‐1 action on living cartilage was heat labile and concentration dependent, with significant effect at 5 U/ml and maximal effect at 10–20 U/ml. Kinetic studies showed significant stimulation of PG release by 3 days of incubation with 10 U/ml IL‐1. Studies in which IL‐1 was removed on day 1 or day 4 showed that the cartilage‐degrading effect of this monokine was reversible. Although IL‐1 caused little change in the Sepharose CL‐2B chromatographic profile of released PGs using an associative elution buffer, a significant shift to lower mol wt was observed under dissociative conditions. To probe the mechanism of IL‐1 action, cartilage samples were incubated with IL‐1 in the presence of the protein synthesis inhibitor, cycloheximide, or the lysosomal membrane‐stabilizing steroid, hydrocortisone. Cycloheximide at 5–10 μg/ml completely blocked IL‐1–induced breakdown. On the other hand, 3 × 10−7M hydrocortisone had little or no effect on IL‐1 action. IL‐1 was also shown to stimulate the degradation of human articular cartilage.