INDEPENDENT EFFECTS OF INTERLEUKIN-1 ON PROTEOGLYCAN SYNTHESIS AND PROTEOGLYCAN BREAKDOWN OF BOVINE ARTICULAR-CARTILAGE IN-VITRO

We studied the effects of human recombinant interleukin-1beta on prote oglycan metabolism of bovine articular cartilage in organ culture. IL- 1 was more potent in inhibiting synthesis (IC50 4 ng/mL) than in stimu lating breakdown of proteoglycans (EC50 200 ng/mL). Inhibition of prot eoglycan synthesis began to plateau earlier (2 days) than stimulation of proteoglycan release (4 days). Both effects could be neutralized wi th a polyclonal anti-IL-1beta antibody; however, higher antibody titer s were required to block IL-1 effects on proteoglycan synthesis than t o neutralize those on proteoglycan release. Chloroquine, but not hydro cortisone, blocked IL-1-mediated proteoglycan breakdown. Both drugs, h owever, augmented IL-1-induced inhibition of proteoglycan synthesis. O ur data suggest that the effects of IL-1 on articular cartilage proteo glycan synthesis and proteoglycan breakdown can be regulated independe ntly.