Human cartilage is degraded by rheumatoid arthritis synovial fluid but not by recombinant cytokines in vitro.

Rheumatoid arthritis (RA) synovial fluid (SF) stimulated significant loss of glycosaminoglycans (GAG) from normal and pathological human cartilage biopsies over 2 days as compared with normal human serum. By contrast, 15 RA SFs failed to degrade killed normal cartilage, and degraded killed RA cartilage less effectively than living RA cartilage. Four RA SFs were treated with neutralizing anti-cytokine antisera prior to incubation with normal cartilage. The degrading effects of two of the fluids were reversed by anti-interleukin-1 alpha (IL-1 alpha) while degradation by the third and fourth fluids were reversed by anti-interleukin-1 beta (IL-1 beta) and anti-tumour necrosis factor-alpha (TNF-alpha), respectively. However, recombinant human IL-1 alpha, IL-1 beta, TNF alpha or a combination of all three cytokines had no degrading effect in this 2-day culture system. It is concluded that RA SF degrades cartilage by a mechanism involving a synergistic interaction between cytokines and some other component of SF.