COOPERATION 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-1β at a concentration of 57 pM 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-1β 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 μg ml-1) or plasminogen (100 μg ml-1), IL-1β (57 pM) casued almost complete degradation of the collagen matrix. Plasmin or plasminogen alone caused only slight degradation of the collagen matrix. 4. Tissue inhibitor of methalloproteinases (TIMP) or the selective metalloproteinase inhibitor, SC 44463, inhibited the degradation induced by IL-1β and plasminogen in a concentration-related manner and at concentrations that were correlated with inhibition of collagenase. 5. When concentrations of IL-1β which caused only minimal degradation of the matrix in the presence of plasminogen were combined with fibrin (1 μg 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.