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

Recent studies have implicated leukemia inhibitory factor (LIF) in human joint disease, LIF is produced by cultured synovial cells and articular chondrocytes, stimulates cartilage and bone resorption, and has been detected in inflammatory exudates from arthritic joints, The aim of this study was to evaluate the effect of intraarticular injections of human recombinant LIF in the goat, Endotoxin-free, sterile normal saline containing 1 mu g recombinant human LIF (rhLIF) was injected into the right radiocarpal joints (RCJs) of eight angora goats. The left RCJs were injected with an equivalent volume of vehicle alone (n = 6) or vehicle containing 1 mu g human albumin (n = 2), Goat joints were examined 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 determined in the SF, Proteoglycan synthesis was determined ex vivo in cartilage explants obtained on day 6 postinjection, A statistically significant increase in joint swelling and effusion volume was observed in LIF-injected joints but not in control joints, In the LIF-injected RCJs, the leukocyte count increased from 82 +/- 9 cells/mu l before injection to 10,300 +/- 3357 cells/mu l at day 2 postinjection (p < 0.005) and declined to 678 +/- 113 cells/mu l at day 6 postinjection, Polymorphonuclear leukocytes and monocyte/macrophages predominated in the infiltrate, No appreciable change in leukocyte counts was observed in control 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 change 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% lower in cartilage from LIF-injected joints (p < 0.01), These results show that rhLIF stimulates proteoglycan catabolism in vivo and that it also probably inhibits proteoglycan synthesis in vivo, The findings also indicate that rhLIF has proinflammatory activity in goat joints.