Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans

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Abstract
Background— Circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are elevated in diabetic patients. We assessed the role of glucose in the regulation of circulating levels of IL-6, TNF-α, and interleukin-18 (IL-18) in subjects with normal or impaired glucose tolerance (IGT), as well as the effect of the antioxidant glutathione. Methods and Results— Plasma glucose levels were acutely raised in 20 control and 15 IGT subjects and maintained at 15 mmol/L for 5 hours while endogenous insulin secretion was blocked with octreotide. In control subjects, plasma IL-6, TNF-α, and IL-18 levels rose ( P P P P P Conclusions— Hyperglycemia acutely increases circulating cytokine concentrations by an oxidative mechanism, and this effect is more pronounced in subjects with IGT. This suggests a causal role for hyperglycemia in the immune activation of diabetes.