Upregulation of enzymatic activity by interleukin-1 in osteoarthritis

Abstract

Osteoarthritis is a slow progressive disease characterized by destruction of the articular cartilage. The degradation of extracellular matrix components is mainly mediated by a family of enzymes, the metalloproteinases (MMPs), which are active at neutral pH. Interleukin-1 (IL-1) is a small peptide, active in autocrine and paracrine fashions. In vitro IL-1 increases the production of MMPs and inhibits the synthesis of collagen type II and proteoglycans. Its role in osteoarthritis is based on several findings: IL-1 is detectable in the synovial fluid and in the cartilage matrix of osteoarthritic joints; in vivo its deleterious actions can be reproduced by intra-articular injection of recombinant IL-1; biochemical changes observed in the cartilage matrix from osteoarthritic joints resemble those induced in vitro by IL-1; finally, antagonists of IL-1 are capable in vivo of preventing or at least diminishing the degradation of cartilage matrix components in several models of experimental arthritis. Interleukin-1 appears to be a main factor mediating cartilage matrix destruction. However, its role in human osteoarthritis, although highly probable, remains to be determined.