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Leukemia inhibitory factor (LIF) binding protein attenuates the phlogistic and abolishes the chondral effects of LIF in goat joints

Bell, M., Carroll, G.J., Chapman, H., Layton, M. and Mills, J. (1997) Leukemia inhibitory factor (LIF) binding protein attenuates the phlogistic and abolishes the chondral effects of LIF in goat joints. Journal of Rheumatology, 24 (12). pp. 2394-2402.


Objective. To investigate the ability of murine leukemia inhibitory factor (LIF) binding protein (mLBP) to attenuate the effects of recombinant human LIF (rhLIF) in goat radiocarpal joints in vivo. Methods. Endotoxin- free saline (1 ml) containing either 0.5 or 1 μg of rhLIF was injected into the left and right radiocarpal joints of male angora goats. One hour later the right radiocarpal joints were injected with either 1 or 5 μg of naturally occurring mLBP in 1 ml saline, while the left radiocarpal joints (controls) received 1 ml saline vehicle alone. Goat joints were examined for clinical features of inflammation and synovial fluid (SF) was aspirated on Day 0 (before injection) and Days 2 and 6 postinjection. Leukocyte counts and concentrations of keratan sulfate were determined in the SF. Proteoglycan synthesis and proteoglycan content of cartilage was determined ex vivo in cartilage explants obtained at Day 6. Results. Preliminary time course studies in vitro showed that mLBP had to be added to cartilage explant cultures within 1 h of rhLIF for effective antagonism to occur. In joints injected with either 0.5 or 1 μg rhLIF significant increases in swelling, effusion volume, leukocyte counts, and SF keratan sulfate concentrations were observed relative to controls. Statistically significant depressions of ex vivo proteoglycan synthesis and in proteoglycan content of articular cartilage were also observed relative to controls. In joints injected with 1 μg rhLIF followed by 1 μg mLBP, statistically significant improvement was only observed in the rate of ex vivo cartilage proteoglycan synthesis. The observed rate did not differ significantly from that obtained in joints treated with vehicle alone. In contrast, in joints injected with 0.5 μg rhLIF followed by 5 μg mLBP, statistically significant improvement was observed in all variables. Treatment with 5 μg mLBP effectively negated the effects of rhLIF on joint swelling, effusion volume, leukocyte infiltration, and cartilage proteoglycan catabolism. Conclusion. Murine LBP has the ability to attenuate the phlogistic effects of rhLIF in radiocarpal joints of goats and also abolishes the stimulatory effect of rhLIF on cartilage proteoglycan catabolism and depression of ex vivo proteoglycan synthesis. These antiinflammatory and chondral effects suggest that a humanized derivative of mLBP could be a clinically useful antagonist for LIF in inflammatory diseases.

Item Type: Journal Article
Murdoch Affiliation(s): School of Veterinary and Biomedical Sciences
Publisher: Journal of Rheumatology
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