Dose-dependent effects of recombinant human interleukin-6 on glucose regulation

J Clin Endocrinol Metab. 1997 Dec;82(12):4167-70. doi: 10.1210/jcem.82.12.4422.


Inflammatory cytokines have metabolic actions that probably contribute to the general adaptation of the organism during infectious or inflammatory stress. To examine the effects of interleukin 6 (IL-6), the main circulating cytokine, on glucose metabolism in man, we performed dose-response studies of recombinant human IL-6 in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/Kg BW) were 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 significant adverse effects. We measured the circulating levels of glucose, insulin, C-peptide, and glucagon at baseline and half-hourly over 4 h after 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, respectively, for the 5 doses. After administration of the 2 smaller IL-6 doses, we observed no significant changes in plasma glucose levels, which, because of continued fasting, decreased slightly over time. By 60 min after the 3 higher IL-6 doses, however, the decline in fasting blood glucose was arrested, and glucose levels increased in a dose-dependent fashion. The concurrent levels of plasma insulin and C-peptide were 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 induced dose-dependent increases in fasting blood glucose, probably by stimulating glucagon release and other counteregulatory hormones and/or by inducing peripheral resistance to insulin action.

MeSH terms

  • Adult
  • Blood Glucose / analysis*
  • C-Peptide / blood
  • Dose-Response Relationship, Drug
  • Glucagon / blood
  • Humans
  • Injections, Subcutaneous
  • Insulin / blood
  • Interleukin-6 / adverse effects
  • Interleukin-6 / pharmacology*
  • Male
  • Recombinant Proteins


  • Blood Glucose
  • C-Peptide
  • Insulin
  • Interleukin-6
  • Recombinant Proteins
  • Glucagon