ROLE OF GLUCOSE IN INTERLEUKIN-1-BETA PRODUCTION BY LIPOPOLYSACCHARIDE-ACTIVATED HUMAN MONOCYTES

When monocytes are activated with endotoxin (lipopolysaccharide [LPS]) , they make and release several mediators, including interleukin-1beta (IL-1beta). This study was undertaken to investigate the role of gluc ose in IL-1beta production by these cells. IL-1beta was produced in a dose-dependent manner to glucose concentration in the culture medium. The uptake of (H-3)2-deoxyglucose in monocytes was stimulated by LPS 1 ,554% after 10 minutes, 6,095% after 2 hours, then gradually declined after 4 hours of incubation. The inhibition of the uptake of (H-3)2-de oxyglucose by either 10 muM cytochalasin B or phloretin, added at the time of monocyte activation, was accompanied by significant reduction in ATP/ADP ratio and the inhibition of the production of IL-1beta by a ctivated monocytes. The synthesis of total protein did not change in m onocytes activated in the absence of glucose in the culture medium, no r in the presence of either 10 muM cytochalasin B or phloretin. The ex port of IL-1beta from LPS-activated monocytes was not inhibited by eit her 10 muM cytochalasin B or phloretin, nor in the absence of glucose in the culture medium. These data suggest that 1) glucose is required for LPS-induced IL-1beta production by monocytes; 2) glucose is the ma jor source of ATP for IL-1beta production; 3) glucose transporter (GLU T 1) does not control the export of IL-1beta. (C) 1993 Wiley-Liss, Inc .