Leukaemia inhibitory factor (LIF) suppresses proteoglycan synthesis in porcine and caprine cartilage explants.

Leukaemia Inhibitory Factor (LIF) has been implicated in connective tissue 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 vitro. The methods used were as follows: slices of pig and goat articular cartilage were incubated overnight in Dulbecco's modification of Eagles medium (DMEM), supplemented with 5% foetal calf serum (FCS) and then cultured for 48 h without FCS and either no cytokines (negative control) or LIF. During the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose-dependent suppression of proteoglycan synthesis was observed with murine and human recombinant LIF in pig and goat cartilage. The degree of inhibition was similar to the maximal suppression observed with IL-1 alpha, but was not IL-1 dependent. In conclusion, LIF is a potent inhibitor of proteoglycan synthesis in cultured pig and goat articular cartilage.