LEUKEMIA INHIBITORY FACTOR INDUCES LEUKOCYTE INFILTRATION AND CARTILAGE PROTEOGLYCAN DEGRADATION IN GOAT JOINTS

Recent studies have implicated leukemia inhibitory factor (LIF) in hum an joint disease, LIF is produced by cultured synovial cells and artic ular chondrocytes, stimulates cartilage and bone resorption, and has b een detected in inflammatory exudates from arthritic joints, The aim o f this study was to evaluate the effect of intraarticular injections o f human recombinant LIF in the goat, Endotoxin-free, sterile normal sa line containing 1 mu g recombinant human LIF (rhLIF) was injected into the right radiocarpal joints (RCJs) of eight angora goats. The left R CJs were injected with an equivalent volume of vehicle alone (n = 6) o r vehicle containing 1 mu g human albumin (n = 2), Goat joints were ex amined for clinical features of inflammation, and synovial fluid (SF) was aspirated on days 0, 2, and 6 postinjection, Leukocyte counts and concentrations of keratan sulfate, IL-1 beta, and TNF-alpha were deter mined in the SF, Proteoglycan synthesis was determined ex vivo in cart ilage explants obtained on day 6 postinjection, A statistically signif icant increase in joint swelling and effusion volume was observed in L IF-injected joints but not in control joints, In the LIF-injected RCJs , the leukocyte count increased from 82 +/- 9 cells/mu l before inject ion to 10,300 +/- 3357 cells/mu l at day 2 postinjection (p < 0.005) a nd declined to 678 +/- 113 cells/mu l at day 6 postinjection, Polymorp honuclear leukocytes and monocyte/macrophages predominated in the infi ltrate, No appreciable change in leukocyte counts was observed in cont rol joints, An increase in synovial fluid keratan sulfate was observed in the LIF-injected RCJs from 70 +/- 0.7 mu g/ml at baseline to 163.6 +/- 12.3 mu g/ml at day 2 postinjection (p < 0.001). There was no cha nge in control joints, At day 6 postinjection, the LIF-injected joint cartilage contained 20.5% less proteoglycan than control cartilage (p < 0.01), In vitro synthesis of proteoglycan was found to be 16.0% lowe r in cartilage from LIF-injected joints (p < 0.01), These results show that rhLIF stimulates proteoglycan catabolism in vivo and that it als o probably inhibits proteoglycan synthesis in vivo, The findings also indicate that rhLIF has proinflammatory activity in goat joints.