INTERLEUKIN-1-BETA-MEDIATED GLUCOSE-UPTAKE BY CHONDROCYTES - INHIBITION BY CORTISOL

The aim of this study was to investigate the in vitro effects of inter leukin-1 beta (IL-1 beta) on cultured human articular chondrocytes fro m patients with osteoarthritis, by the evaluation of glucose uptake. W e also investigated the inhibitory effect of cortisol on IL-1 beta-med iated glucose uptake. Experiments were performed by using 2-deoxy-D-[1 -H-3]glucose (2-DOG) and confluent monolayer cells at first passage. C onfluent cells were also treated for 24 h with different concentration s of cortisol (10(-5), 10(-6) and 10(-7) mol/l). IL-1 beta (100 pg/ml) was added 6 h before glucose uptake studies. Glucose uptake stimulati on was observed 3 h after the addition of 100 pg/ml IL-1 beta (+70%) a nd increased up to 24 h (+145%). The sensitivity and responsiveness of chondrocytes to IL-1 beta, studied after a 6 h association time, appe ared to be dose-dependent from 0.1 pg/ml IL-1 beta (+50%) to 100 pg/ml (+130%) over basal values. The effect of the cytokine was protein syn thesis-dependent, as demonstrated by using cycloheximide. Cortisol inh ibited the action of IL-1 beta on glucose uptake because it reduced st imulating effects by 28% at concentrations as weak as 10(-6) mol/l. Re sults appeared similar when IL-1 beta and cortisol were added simultan eously 6 h before 2-DOG uptake. The rapid effect of cortisol was prote in-synthesis dependent, as indicated by inhibition by cycloheximide. T hese results suggest that IL-1 beta stimulates chondrocyte metabolic a ctivity. The inhibition of IL-1 beta-mediated glucose uptake is sugges ted for studying the anti-IL-1 effect of other anti-rheumatic drugs.