Glucose Modifies the Immune Interaction Between Mononuclear and Human Colon Carcinoma Cells

Abstract

Background: Glucose is one of the principal energy suppliers for normal cell development. Impaired glucose metabolism may lead to serious health and immune impediments including carcinogenesis. The question posed in the present work was if glucose, at several concentrations, affects cytokine production by normal human peripheral blood mononuclear cells (PBMC) and if glucose is able to modulate the immune balance between PBMC and colon cancer cells. Methods: PBMC and human colon cancer cells from HT-29 and RKO lines were separately incubated with glucose at concentrations of 1.25, 2.5 and 5 mg/ml and the capacity for production of TNFα, IL-1?, IL-6, IFNγ, IL-1ra IL- 10, and IL-2 was examined. In another set of experiments the effect of glucose on the secretion of these cytokines by PBMC co-incubated with carcinoma cells was evaluated. Results: Unstimulated PBMC incubated with glucose showed a slight to moderate inhibition of IFNγ and IL-10 secretion, whereas PBMC stimulated with LPS were not affected. Addition of glucose to PBMC stimulated by HT- 29 colon carcinoma cells showed a slight spurring of TNFα production and a marked inhibition of IL-1β, IFNγ and IL-10, an effect significantly less pronounced when glucose was added to co-cultures of PBMC with RKO cells. Conclusions: Glucose exerted an inhibitory effect on inflammatory cytokine production by PBMC stimulated by HT-29 carcinoma cells except for TNFα and IL-6. The results indicate that glucose alters the immune dialog between mononuclear and cancer cells, a phenomenon that may present an additional link between hyperglycemia and carcinogenesis.