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 micrograms 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 micrograms 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/microliters before injection to 10,300 +/- 3357 cells/microliters at day 2 postinjection (p < 0.005) and declined to 678 +/- 113 cells/microliters at day 6 postinjection. Polymorphonuclear leukocytes and monocyte/macrophages predominated in the infiltrate. No appreciable change in leukocyte counts was observed in control joints.(ABSTRACT TRUNCATED AT 250 WORDS)
Carroll
G J
GJ
Department of Rheumatic Diseases, Royal Perth Hospital, Australia.
Bell
M C
MC
Chapman
H M
HM
Mills
J N
JN
Robinson
W F
WF
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D005069:Evaluation Studies as Topic; D005121:Extremities; D006041:Goats / Q000378:metabolism*; D006131:Growth Inhibitors / Q000494:pharmacology*; D007270:Injections, Intra-Articular; D015850:Interleukin-6; D007632:Keratan Sulfate / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D007958:Leukocyte Count / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects*; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013582:Synovial Fluid / Q000378:metabolism
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D011509:Proteoglycans; D011994:Recombinant Proteins; D007632:Keratan Sulfate