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 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.
Tsigos
C
C
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Papanicolaou
D A
DA
Kyrou
I
I
Defensor
R
R
Mitsiadis
C S
CS
Chrousos
G P
GP
D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D002096:C-Peptide / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000097:blood; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D011994:Recombinant Proteins
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D015850:Interleukin-6; D011994:Recombinant Proteins; D005934:Glucagon