Effects of 2-deoxy-d-glucose administration on immune parameters in mice

Dréau, Didier; Morton, Darla S.; Foster, Mareva; Fowler, Nina; Sonnenfeld, Gerald

doi:10.1016/s0162-3109(98)00016-2

Cited by 14 publications

(12 citation statements)

References 33 publications

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“…Indeed, it is well described that upon activation T cells rapidly switch metabolic programs from fatty acid β-oxidation and pyruvate oxidation via the tricarboxylic acid cycle to aerobic glycolysis, pentose-phosphate pathway, and glutaminolysis (25). However, several in vivo studies described that the effect of 2DG on T-cell activation and proliferation was minor in the mouse strains we used in our study (C57BL/6 and BALB/c) (26,27), even when those animals received several injections of 2,000 mg/kg of 2DG (four times more than the classical dose used in most studies, including ours) (26). In this line, we established that functional and active tumor-specific cytotoxic T cells could be isolated from the spleen of cotreated animals ( Fig.…”

Section: Discussionmentioning

confidence: 73%

Combination of glycolysis inhibition with chemotherapy results in an antitumor immune response

Bénéteau

Zunino

Jacquin

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Most DNA-damaging agents are weak inducers of an anticancer immune response. Increased glycolysis is one of the best-described hallmarks of tumor cells; therefore, we investigated the impact of glycolysis inhibition, using 2-deoxyglucose (2DG), in combination with cytotoxic agents on the induction of immunogenic cell death. We demonstrated that 2DG synergized with etoposide-induced cytotoxicity and significantly increased the life span of immunocompetent mice but not immunodeficient mice. We then established that only cotreated cells induced an efficient tumor-specific T-cell activation ex vivo and that tumor antigen-specific T cells could only be isolated from cotreated animals. In addition, only when mice were immunized with cotreated dead tumor cells could they be protected (vaccinated) from a subsequent challenge using the same tumor in viable form. Finally, we demonstrated that this effect was at least partially mediated through ERp57/calreticulin exposure on the plasma membrane. These data identify that the targeting of glycolysis can convert conventional tolerogenic cancer cell death stimuli into immunogenic ones, thus creating new strategies for immunogenic chemotherapy.

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Section: Discussionmentioning

confidence: 73%

Combination of glycolysis inhibition with chemotherapy results in an antitumor immune response

Bénéteau

Zunino

Jacquin

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Administration of 2-DG, a nonmetabolizabl e glucose analog that reproduces all the hallmarks of intense exercise (7) and provokes acute intracellular glucoprivation and extracellular hyperglycemia, (9,10) has been studied previously in female mice, (12,14,21) male rats, (15,16) and humans. (17) Changing the time of 2-DG injections produced comparable physiologic changes in mice (12,14) and rats (22) during the light phase, as well as in rats (15) studied in reverse dark/light cycle.…”

Section: Discussionmentioning

confidence: 99%

“…Injections, administered 1.5 h into the light phase of the day cycle, were perform ed once every 48 h as previously described. (12 ) All mice were deprived of food for 2 h after the injection. Mice were rapidly killed with CO 2 2 h after the final injection of saline of 2-DG.…”

Section: Experimental Injectionsmentioning

confidence: 99%

“…(7,8) 2-DG prevents the cellular uptake and utilization of glucose, which causes acute intracellular glucoprivation and extracellular hyperglycemia. (9,10) 2-DG adm inistration was mostly followed in many species, including mice, (11)(12)(13)(14) rats, (15,16) and humans, (17) by hormonal and immunologic changes. The hormonal alterations included changes in glucocorticoids, (1 1,12,15) corticotropin-rele asing hormone, and catecholam ine (16,17) concentrations.…”

Section: Introductionmentioning

confidence: 99%

“…(13) This was further supported by 2-D G-enhanced resistance to Listeria monocytogenes infection in mice. (19) In vitro proliferation of T lymphocytes isolated from the spleen was drastically decreased in mice, (11)(12)(13)(14) rats, (15) and humans. (17 ) All these immune alterations were associated with increased IL-1 production in the blood (11) and after in vitro stimulation with lipopolysaccharid es (LPS) of splenocytes.…”

Section: Introductionmentioning

confidence: 99%

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Effects of 2-Deoxy-D-Glucose Administration on Cytokine Production in BDF₁ Mice

Dréau

Morton²,

Foster³

et al. 2000

Journal of Interferon & Cytokine Research

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Physical exercise and diet changes have been shown to affect immune parameters, and similar effects are also induced by the administration of a nonmetabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The present study was designed to characterize the effects of glucoprivation induced by 2-DG administration on concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the blood and interferon-gamma (IFN-gamma), IL-2, and IL-4 in vitro production by partially purified T splenocytes in BDF1 mice. Mice (n = 8 per group) were injected intraperitoneally one or three times with 0, 500, 750, or 1000 mg/kg of 2-DG, and blood and spleens were collected 2 h after the last injection. Partially purified T splenocytes were cultured 24 h in the presence of concanavalin A (ConA). A significant increase in the corticosterone levels with the amount of 2-DG injected was observed after one or three injections (p<0.05). The amount of 2-DG injected was associated with an increase in TNF-alpha, IL-1beta, and IL-6 concentrations in the blood of mice after one or three injections of 2-DG (p<0.05). A significant decrease in in vitro proliferation of partially purified splenocytes in the presence of ConA was associated with a decrease in IFN-gamma production in the culture supernatants and an increase in IL-1 receptor expression on the cell surface (p<0.05).

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Sex-specific effects of glucose deprivation on cell-mediated immunity and reproduction in Siberian hamsters (Phodopus sungorus)

et al. 2008

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In most species, sexes differ in levels of parasitism. These differences have traditionally been believed to be static, but a capacity for adjusting anti-parasite investments would allow sexes to allocate resources adaptively contingent on environmental conditions. During stressful periods, such as a food shortage, allocation decisions would be mandated in males and females, but the biasing of resources may differ depending on the value of various physiological alternatives to the fitness of each sex. To determine whether sexes sacrifice immune or reproductive capacity when stressed, male and female Siberian hamsters (Phodopus sungorus) were pharmacologically deprived of glucose. Glucose deprivation was expected to compromise immune activity (delayed-type hypersensitivity) more than reproductive capacity in males because male fitness is limited by reproductive opportunities. The opposite was predicted for females because of the greater value of surviving to breed in favorable conditions. Contrary to expectations, glucoprivation compromised immune activity in female, but not male, hamsters. Conversely, glucoprivation reduced male, but not female, reproductive organ masses. These results may reflect the adjustments made by wild hamsters during food shortages, or they may be influenced by the study design; neither sex was permitted to incur other behavioral and physiological costs, such as lactation and parental care. Regardless, our results indicate that sex differences in parasitism are likely to be plastic in many circumstances, but further work in free-living animals is critical to ascertain whether results of the present study are naturally representative.

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Effects of 2-deoxy-d-glucose administration on immune parameters in mice

Cited by 14 publications

References 33 publications

Combination of glycolysis inhibition with chemotherapy results in an antitumor immune response

Combination of glycolysis inhibition with chemotherapy results in an antitumor immune response

Effects of 2-Deoxy-D-Glucose Administration on Cytokine Production in BDF₁ Mice

Sex-specific effects of glucose deprivation on cell-mediated immunity and reproduction in Siberian hamsters (Phodopus sungorus)

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Effects of 2-deoxy-d-glucose administration on immune parameters in mice

Cited by 14 publications

References 33 publications

Combination of glycolysis inhibition with chemotherapy results in an antitumor immune response

Combination of glycolysis inhibition with chemotherapy results in an antitumor immune response

Effects of 2-Deoxy-D-Glucose Administration on Cytokine Production in BDF1 Mice

Sex-specific effects of glucose deprivation on cell-mediated immunity and reproduction in Siberian hamsters (Phodopus sungorus)

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Effects of 2-Deoxy-D-Glucose Administration on Cytokine Production in BDF₁ Mice