The kinetics of hyaluronan in normal and acutely inflamed synovial joints: Observations with experimental arthritis in sheep

The metabolic half-life of hyaluronan (HA) in synovial fluid was estimated in sheep from the rate of appearance of 3 H 2 O in plasma after injection of highly polymerized labeled HA. This material is substituted with 3 H in its acetyl group and is rapidly and almost completely degraded in sheep and other species to yield 3 H 2 O. Previously sensitized sheep were studied before and after induction of acute monoarticular arthritis by intraarticular challenge with type II collagen. In both circumstances 3 H was released from the joint in a monophasic exponential pattern and appeared in plasma only as 3 H 2 O. Before challenge, the mean metabolic half-life of [ 3 H]HA was 20.8 hours (range, 15.8 to 27.9 hours, n=5); an estimate in a single unsensitized sheep (27.0 hours) fell within this range. After challenge, swelling occurred around the joint without frankly increased synovial fluid. The mean half-life fell to 11.5 hours (range, 9.0 to 16.8 hours), with a corresponding increase in mean fractional turnover from 3.5%/h to 6.3%/h; an increased amount of the label was also retained within the peripheral tissues. It is concluded that a relatively mild acute inflammation can induce major changes in the metabolic turnover of synovial HA without the development of gross effusions. In the course of this study, mean synovial fluid volume in the normal sheep hock joint was estimated to be 1.54 mL; the concentration and content of HA were 0.54 mg/mL and 0.84 mg, respectively. These data add to other evidence that the volume and HA content of normal synovial fluid vary widely in different joints and species. However, it is unlikely that such differences could materially influence changes in HA metabolism of the order recorded here in response to synovial inflammation.