Hypoglycaemia downregulates endotoxin-induced production of tumour necrosis factor-alpha, but does not affect IL-1beta, 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 pmolm(-2) x min(-1)) stepped hypoglycaemic (5.0-3.5-2.5 mmoll(-1)) glucose clamps were performed in eight diabetic patients and in six non-diabetic subjects, and hyperinsulinaemic normoglycaemia (5.0 mmoll(-1)) control experiments were performed in four non-diabetic 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, hypoglycaemia 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 normoglycaemia (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.
de Galan
B E
BE
Department of General Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands.
Netea
M G
MG
Smits
P
P
van der Meer
J W M
JW
D000328:Adult; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007375:Interleukin-1 / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007328:Insulin; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10