Recombinant interleukin-1 (IL-1) alpha and beta stimulated significant loss of glycosaminoglcan (GAG) content from normal (non-arthritic) articular cartilage explants but only after incubation for 14 days and only in specimens from 8/21 (38%) individuals. By contrast, all cartilage specimens but one from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were degraded (as judged by their reduced GAG content) by the recombinant cytokines but again only after 14 days' incubation. The reduction in GAG induced by IL-1 was also greater for both OA and RA cartilage than normal cartilage. Synovial fluids (SFs) from RA patients stimulated greater loss of GAG content from OA cartilage explants than normal explants although in both cases the loss was evident within 2 days. It is concluded that cartilage explants from some individuals are susceptible to the degradative effects of IL-1 whereas others are refractory and that arthritic cartilage is more susceptible to degradation by both IL-1 and RA SFs than non-arthritic cartilage.

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Human cartilage biopsies incubated for 2 days in-vitro with 15% synovial fluid from rheumatoid arthritis patients contained less glycosaminoglycans (GAG) than control biopsies. Recombinant human (rHu)-interleukin-1 alpha (IL-1 alpha) and IL-1 beta at 10 or 100 ng mL-1 had no effect on human cartilage GAG levels. Similarly, GAG loss from human cartilage biopsies into medium over 5 days was significantly increased by synovial fluid but unaffected by 100 ng mL-1 IL-1 alpha or IL-1 beta compared with controls. However, when rat femoral head cartilage samples were incubated with 100 ng mL-1 rHu-IL-1 alpha or IL-1 beta for 5 days there was a significant increase in GAG loss from the cartilage into medium, whilst human synovial fluid significantly decreased the loss of GAG from rat cartilage into medium, compared with controls. The results demonstrate that human and rat cartilage differ from each other in their responses to degrading stimuli and suggest that animal cartilage may have limited application for the screening of drugs intended for the treatment of human arthritides.

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