The long-term objectives of this proposal are to establish biochemical mechanisms underlying continued cartilage destruction in staphylococcal bacterial arthritis and to develop therapeutic regimens to prevent post-infectious inflammatory cartilage destruction. The rationale for the experiments is based on our results showing that staphylococcal joint infection results in rapid, direct effects on cartilage degradation and loss of proteoglycan and that cartilage destruction continues in spite of antibiotic treatment. The hypotheses to be tested are: (a) that antibiotic treatment coupled with treatment of the host-inflammatory reaction will decrease staph-induced cartilage degradation and (b) that inhibiting the post-infectious inflammatory reaction will prevent continued cartilage destruction and stimulate cartilage recovery. The Specific Aims are: (1a) Characterize long-term staph-induced cartilage degradation following antibiotic treatment at 24 and 48 hours post-infection at three, six and twelve months and (lb) determine short term (3 weeks post-infection) effects of adding supplemental anti-inflammatory treatment coincident with onset of antibiotic therapy; (2) Assess the recuperative capacity of articular cartilage in vitro following onset of cartilage degradation and in vivo following antibiotic and antiinflammatory therapy; (3) Isolate the staphylococcal proteoglycan releasing factor and characterize the molecular basis of staph factor induced cartilage degradation in vitro; (4) Prepare antibodies to the staph factor and apply the antibodies to the onset of staph induced cartilage destruction and test the antibody reactivities against interleukin 1. Experiments will be carried out in our established in vitro and in vivo models of staph infectious arthritis; effects of antibiotic and anti-inflammatory therapies will be assessed by quantitation of cartilage proteoglycan synthesis and degradation. Anti- inflammatory treatment will consist of administration of corticosteroids, nonsteroidal anti-inflammatory reagents and interleukin 2. Additional anti-inflammatory regimens will include aspiration with metal dependent enzyme inhibitors and non-ionic detergents. Purification of the staph factor will include FPLC ion-exchange chromatography.