Differential regulation of human blood glucose level by interleukin-2 and -6

While the acute phase reaction to infection is associated with hyperglycemia, during progressing infection hypoglycemia can develop. The cytokines regulating the dynamics of host defense may concurrently contribute to blood glucose regulation. To examine this hypothesis, changes in blood glucose concentrations in healthy men were compared following administration of interleukin-2 (IL-2) and IL-6 representing, respectively, major mediators of the adaptive and the early innate immune response to bacterial infection. Doses of 10 000 IU/kg IL-2 and 0.5 μg/kg IL-6 (vs. placebo) were administered subcutaneously in two groups of men (n = 18 and 16) at 1900 h before a period of nocturnal rest allowing an assessment of changes under basal conditions. Serum concentrations of glucose and of various hormones were assessed every 60 min. Despite generally lowered glucose concentration at night, IL-2 induced a transient but distinct decrease in blood glucose concentration most consistent 8-9 hours following injection (p < 0.01 ). The hypoglycemic response to IL-2 was not accompanied by changes in serum insulin, C-peptide or cortisol. In contrast to IL-2, IL-6 led to an increase in cortisol, followed by a pronounced increase in blood glucose again peaking about 8 hours after injection (p < 0.001). Results indicate a differential regulation of blood glucose concentration by cytokines. Contrasting with the hyperglycemic effects of the acute phase regulator IL-6, the T-cell cytokine IL-2 seems to support glucose uptake and utilization by immune cells.