CHARACTERIZATION OF THE EFFECT OF 2-DEOXY-D-GLUCOSE (2-DG) ON THE IMMUNE-SYSTEM

This study was designed to characterize the effects of the metabolic s tress of administration of 2-deoxy-D-glucose (2-DG, 500 mg/kg) on immu ne function. Male Lewis rats were exposed to one or five injections (o ne every 48 h) of 2-DG. Control rats received saline injections. Admin istration of 2-DG induced a reduction of total leukocytes in the splee n, thymus, and blood. The reduction was most prominent in animals that received five injections of 2-DG. The ratio of CD4(+)/CD8(+) in the s pleen was decreased due to a significant increase of CD8(+) T-cell sub population Additionally, 2-DG induced a suppression of mitogenic respo nsiveness and IFN-gamma production in both whole blood and spleen lymp hocytes. The production of IL-1 and IL-2 was significantly reduced in the blood, but not in the spleen. Conversely, there was a significant increase in nitric oxide production in cultures of Con A-, PHA-, and L PS-stimulated splenocytes from 2-DG-injected animals compared with sal ine-injected controls. In blood cultures stimulated with Con A and PHA , the nitric oxide production of the group that received five injectio ns of 2-DG was significantly higher than in the group that received on e injection of 2-DG or saline. These results demonstrated that the met abolic stress 2-DG induced a downregulation of Th 1 cellular immune fu nction in a manner similar to physical and psychological stressors. Ad ditionally, the use of 2-DG in rats provided an important model with w hich to study metabolic stress. (C) 1996 Academic Press.