Effect of Purified Human Interleukin-1 on Cartilage Degradation

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 micrograms/ml completely blocked IL-1-induced breakdown. One the other hand, 3 x 10(-7) M hydrocortisone had little or no effect on IL-1 action. IL-1 was also shown to stimulate the degradation of human articular cartilage.