IL-1-BETA, A STRONG MEDIATOR FOR GLUCOSE-UPTAKE BY RHEUMATOID AND NONRHEUMATOID CULTURED HUMAN SYNOVIOCYTES

Higher basal 2-deoxy-D-glucose uptake in rheumatoid synovial cells than in non-rheumatoid synovial cells, was found to be associated with an increased interleukin-1-beta (IL-1-beta) secretion (respectively 850 +/- 238 vs. 8.3 +/- 2.4 pg/24 h/10(5) cells, mean +/- S.E.M.). When exogenous human recombinant IL-1-beta was added to cultures, a marked stimulation of 2-deoxy-D-glucose uptake was performed by both human synovial cultured cells, in a time-dependent and dose-dependent manner (IL-1-beta 0-100 ng/ml). In non-rheumatoid synoviocytes, stimulation occurred 1-3 h following the addition of 1 ng/ml interleukin-1-beta and increased up to 24 hours (respectively +150% and +261.4% after 6 and 24 hours association time). Rheumatoid synovial cells were less sensitive to 1 ng/ml IL-1-beta (respectively +80% and +146.4%). IL-1-beta increased significantly the V(max) for 2-deoxy-D-glucose uptake by synovial cells, with no change in the K(m). This effect was protein synthesis-dependent, and not secondary to prostaglandin E2 synthesis or cell growth. IL-1-beta possesses an important effect on glucose homeostasis in synovial cells, which could be indirect and/or regulated by the presence of natural inhibitors.