DOSE-DEPENDENT EFFECTS OF RECOMBINANT HUMAN INTERLEUKIN-6 ON GLUCOSE REGULATION

Inflammatory cytokines have metabolic actions that probably contribute to the general adaptation of the organism during infectious or inflam matory stress. To examine the effects of interleukin 6 (IL-6), the mai n circulating cytokine, on glucose metabolism in man, we performed dos e-response studies of recombinant human IL-6 in normal volunteers. Inc reasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/Kg BW) w ere injected sc in 15 healthy male volunteers (3 in each dose) after a 12-h fast. All IL-6 doses were tolerated well and produced no signifi cant adverse effects. We measured the circulating levels of glucose, i nsulin, C-peptide, and glucagon at baseline and half-hourly over 4 h a fter the IL-6 injection. Mean peak plasma levels of IL-6 were achieved between 120 and 240 min and were 8, 22, 65, 290, and 4050 pg/mL, resp ectively, for the 5 doses. After administration of the 2 smaller IL-6 doses, we observed no significant changes in plasma glucose levels, wh ich, because of continued fasting, decreased slightly over time. By 60 min after the 3 higher IL-6 doses, however, the decline in fasting;bl ood glucose was arrested, and glucose levels increased in a dose-depen dent fashion. The concurrent levels of plasma insulin and C-peptide we re not affected by any IL-6 dose. In contrast, IL-6 caused significant increases in plasma glucagon levels, which peaked between 120 and 150 min after the IL-6 injection. In conclusion, sc IL-6 administration i nduced dose-dependent increases in fasting blood glucose, probably by stimulating glucagon release and other counteregulatory hormones and/o r by inducing peripheral resistance to insulin action.