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