Inhibition of interleukin 1 induced rat and human cartilage degradation in vitro by the metalloproteinase inhibitor U 27391

Correspondence to: Dr M P Seed, Departments of Experimental Pathology and Rheumatology, St Bartholomew's Hospital Medical College, Charterhouse Square, London ECIM 6BQ, United Kingdom. Accepted for publication 20 August 1992 Abstract Interleukin 1 induced proteoglycan loss from cartilage in vitro was prevented by a biochemical inhibitor of metalloproteinase activity. The inhibitor also partially relieved the inhibition of proteoglycan synthesis caused by interleukin 1. The loss of glycosaminoglycan by rat and human femoral head cartilage in response to human recombinant interleukin 1, (rhIL-1p3) was established, and the modulation of this loss by the metailoproteinase inhibitor U27391 was investigated. Rat femoral head cartilage consistently lost glycosaminoglycan in response to rhIL-l1 whereas only a proportion (30%) of normal human femoral head cartilage did so. Concentrations of 10-100 tmol/l U27391 inhibited the action of rhIL-1l on rat femoral head cartilage, reversing both the loss of glycosaminoglycan and the inhibition of glycosaminoglycan synthesis. U27391 also prevented the reduction in glycosaminoglycan content ofthose human femoral head cartilage explants responsive to rhIL-13. Metalioproteinase inhibition therefore prevents rhIL-1 induced glycosaminoglycan loss by rat and human femoral head cartilage, suggesting that inhibitors of such enzymes may prove to be of therapeutic benefit in erosive diseases in humans.