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‐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) 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‐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.