Dose-Dependent Effects of Recombinant Human Interleukin-6 on Glucose Regulation

Abstract

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.

Porównanie ekspresji IL6 w leukocytach pacjentek z cukrzycą ciążową (GDM) diagnozowanych zgodnie z kryteriami Polskiego Towarzystwa Diabetologicznego z 2011 i 2014 roku

“…Nevertheless, there was a significant positive correlation of leukocyte IL6 gene expression with two-hour postload glucose concentration in the entire study group, suggesting that a change of leukocyte IL6 expression can be related with a role of IL-6 in regulating blood glucose levels during pregnancy. In line with this, increased blood glucose after IL-6 infusion in healthy individuals [33], as well as a direct stimulatory effect of IL-6 on hepatic glucose release from glycogen pools by inhibiting glycogen synthase [34], was shown. On the other hand, we cannot exclude the possibility that high glucose conditions may induce the production of greater amounts of IL-6.…”

Placental infiltration of inflammatory markers in gestational diabetic women

“…IL-6 has been shown to be implicated in pathogenesis of type 2 diabetes and is considered as a strong predictor of insulin resistance in pregnancy (Richardson and Carpenter 2007). The increase of IL-6 mRNA expression in the placenta of GDM mothers may be playing a role in the induction of diabetes (Tsigos et al 1997).…”

Palmitate, but Not Unsaturated Fatty Acids, Induces the Expression of Interleukin-6 in Human Myotubes through Proteasome-dependent Activation of Nuclear Factor-κB

“…The liver is a likely target of IL-6 produced by skeletal muscle and adipose tissue. IL-6 has been shown to increase blood glucose through elevated hepatic glucose output (15,16) and to act as a lipolytic hormone (17). IL-6 also appears to play an important role in mediating insulin resistance in the liver, as has been shown by both IL-6 infusion in vivo in mice (18) and on a cellular level in hepatocytes (19,20).…”