Co-operation between interleukin-1 and the fibrinolytic system in the degradation of collagen by articular chondrocytes.

1. The interaction between interleukin 1 (IL-1) and the fibrinolytic system in the control of collagen degradation by rabbit chondrocytes has been investigated in a tissue-culture system where cells are grown on a 14C-labelled collagen matrix. 2. Culture of rabbit chondrocytes in the presence of human recombinant IL-1 beta at a concentration of 57pM for 48 h led to the presence of procollagenase but not active collagenase in the medium. The latent collagenase could be activated by incubation with an organomercurial, aminophenylmercuric acetate (APMA). 3. Addition of IL-1 beta to chondrocytes grown on a 14C-labelled collagen matrix did not increase the degradation of the matrix compared to control over a 48 h period. However, in the presence of plasmin (200 micrograms ml-1) or plasminogen (100 micrograms ml-1), IL-1 beta (57 pM) caused almost complete degradation of the collagen matrix. Plasmin or plasminogen alone caused only slight degradation of the collagen matrix. 4. Tissue inhibitor of metalloproteinases (TIMP) or the selective metalloproteinase inhibitor, SC44463, inhibited the degradation induced by IL-1 beta and plasminogen in a concentration-related manner and at concentrations that were correlated with inhibition of collagenase. 5. When concentrations of IL-1 beta which caused only minimal degradation of the matrix in the presence of plasminogen were combined with fibrin (1 microgram ml-1), there was almost total degradation of the matrix by 48 h. 6. These results indicate there is a synergistic interaction between IL-1 and the fibrinolytic system in the degradation of collagen by rabbit chondrocytes in culture.