INTERLEUKIN-1 AND ONCOSTATIN-M IN COMBINATION PROMOTE THE RELEASE OF COLLAGEN FRAGMENTS FROM BOVINE NASAL CARTILAGE IN CULTURE

Interleukin-1 (IL-1) and Oncostatin M (OM) induce a rapid and reproducible release of proteoglycan and collagen fragments from bovine nasal cartilage in culture. Over 90% of the total collagen was released by day 14 compared to a variable release with IL-1 alone. This release was accompanied by the appearance of collagenolytic activity in the medium that cleaved collagen specifically at the one quarter/three quarter position. Tissue inhibitor of metalloproteinases (TIMP-1) activity was low or absent in media from resorbing tissue. The breakdown of cartilage collagen could be prevented by the addition of BB94, a specific matrix metalloproteinase (MMP) inhibitor. These results suggest that T-cell/macrophage products within inflammed joints can interact with pro-inflammatory cytokines and lead to the rapid destruction of connective tissue collagen. (C) 1995 Academic Press, Inc.