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 stress of administration of 2-deoxy-d-glucose (2-DG, 500 mg/kg) on immune function. Male Lewis rats were exposed to one or five injections (one every 48 h) of 2-DG. Control rats received saline injections. Administration of 2-DG induced a reduction of total leukocytes in the spleen, thymus, and blood. The reduction was most prominent in animals that received five injections of 2-DG. The ratio of CD4(+)/CD8(+) in the spleen was decreased due to a significant increase of CD8(+) T-cell subpopulation. Additionally, 2-DG induced a suppression of mitogenic responsiveness and IFN-gamma production in both whole blood and spleen lymphocytes. 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 LPS-stimulated splenocytes from 2-DG-injected animals compared with saline-injected controls. In blood cultures stimulated with Con A and PHA, the nitric oxide production of the group that received five injections of 2-DG was significantly higher than in the group that received one injection of 2-DG or saline. These results demonstrated that the metabolic stress 2-DG induced a downregulation of Th 1 cellular immune function in a manner similar to physical and psychological stressors. Additionally, the use of 2-DG in rats provided an important model with which to study metabolic stress.