Interleukin-1 β-mediated glucose uptake by chondrocytes. Inhibition by cortisol

Abstract

The aim of this study was to investigate the in vitro effects of interleukin-1 beta (IL-1 beta) on cultured human articular chondrocytes from patients with osteoarthritis, by the evaluation of glucose uptake. We also investigated the inhibitory effect of cortisol on IL-1 beta-mediated glucose uptake. Experiments were performed by using 2-deoxy-D-[1-3H]glucose (2-DOG) and confluent monolayer cells at first passage. Confluent cells were also treated for 24 h with different concentrations 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 stimulation was observed 3 h after the addition of 100 pg/ml IL-1 beta (+70%) and increased up to 24 h (+145%). The sensitivity and responsiveness of chondrocytes to IL-1 beta, studied after a 6 h association time, appeared 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 synthesis-dependent, as demonstrated by using cycloheximide. Cortisol inhibited the action of IL-1 beta on glucose uptake because it reduced stimulating effects by 28% at concentrations as weak as 10(-6) mol/l. Results appeared similar when IL-1 beta and cortisol were added simultaneously 6 h before 2-DOG uptake. The rapid effect of cortisol was protein-synthesis dependent, as indicated by inhibition by cycloheximide. These results suggest that IL-1 beta stimulates chondrocyte metabolic activity. The inhibition of IL-1 beta-mediated glucose uptake is suggested for studying the anti-IL-1 effect of other anti-rheumatic drugs.