Hypoglycaemia downregulates endotoxin-induced production of tumour necrosis factor-α, but does not affect IL-1β, IL-6, or IL-10

The aim of the present study was to investigate the effect of hypoglycaemia on the production capacity of the proinflammatory cytokines tumour necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) in subjects with and without diabetes. Hyperinsulinaemic (360 pmol m(-2) min(-1)) stepped hypoglycaemic (5.0-3.5-2.5 mmol 1(-1)) glucose clamps were performed in eight diabetic patients and in six non-diabetic subjects, and hyperinsulinaemic normoglycaemia (5.0 mmol 1(-1)) control experiments were performed in four nondiabetic subjects. Circulating levels of cytokines and endotoxin-induced production of TNFalpha, IL-1beta IL-6, and IL-10 were assessed. The effects of insulin and adrenaline were measured in separate in vitro experiments. In non-diabetic subjects, hypoglycaernia downregulated the production capacity of TNFalpha in a concentration-dependent fashion (P = 0.007), but not of IL-1beta, IL-6, or IL-10. Compared to controls, the production capacity of TNFalpha in diabetic patients was already suppressed at normoglycaernia (P = 0.02) and only fell in response to hypoglycaemic nadir (P = 0.04). The downregulation of TNFalpha could not be explained by increased insulin or adrenaline levels. We conclude that hypoglycaemia specifically downregulates TNFalpha production capacity. Diabetic patients already have a suppressed TNFalpha production capacity at non-hypoglycaemic levels. (C) 2003 Elsevier Science Ltd. All rights reserved.