LEUKEMIA INHIBITORY FACTOR (LIF) SUPPRESSES PROTEOGLYCAN SYNTHESIS INPORCINE AND CAPRINE - CARTILAGE EXPLANTS

Leukaemia Inhibitory Factor (LIF) has been implicated in connective ti ssue damage in arthritis. We have previously shown that LIF stimulates proteoglycan release in pig cartilage explants. The aim of this study was to determine whether LIF modulates proteoglycan synthesis in vitr o. The methods used were as follows: slices of pig and goat articular cartilage were incubated overnight in Dulbecco's modification of Eagle s medium (DMEM), supplemented with 5% foetal calf serum (FCS) and then cultured for 48 h without FCS and either no cytokines (negative contr ol) or LIF, During the final 6 h the tissue was cultured in sulphate f ree DMEM containing (SO4)-S-35. The radioactivity in the medium and ti ssue was determined in cetylpyridinium chloride precipitates, Biosynth etic activity was expressed as DPM per mg wet weight of cartilage. Dos e-dependent suppression of proteoglycan synthesis was observed with mu rine and human recombinant LIF in pig and goat cartilage, The degree o f inhibition was similar to the maximal suppression observed with IL-1 alpha, but was not IL-1 dependent. In conclusion, LIF is a potent inh ibitor of proteoglycan synthesis in cultured pig and goat articular ca rtilage.