The role of interleukin-6 (IL-6) in carbohydrate metabolism beyond its
inhibition of hepatic phosphoenolpyruvate carboxykinase has not been
widely pursued. To describe such IL-6 effects, we examined in the rat
the responses of plasma corticosterone, glucagon, insulin, and glucose
levels and the hepatic glycogen content 30, 60, 90, 120, and 180 min
after intravenous injection of recombinant human IL-6. The effect to i
ncrease plasma corticosterone was con son ant with the well-known acti
on of IL-6 on the hypothalamus-pituitary-adrenal cortex. IL-6 produced
a transient increase in plasma glucagon that was mirrored by elevated
plasma glucose and a depletion of hepatic glycogen. Plasma insulin le
vels were not elevated within the first hour after IL-6 injection but
were significantly elevated 90 min and beyond. We suggest that the sti
mulus for increased circulating insulin was elevated plasma glucose, r
ather than a direct effect of IL-6. The results demonstrate that IL-6,
acting directly on peripheral organs and/or through the central nervo
us system (CNS) can alter the hormonal and carbohydrate milieu. We pro
pose that these actions of IL-6 are one aspect of its role in the acut
e phase response. (C) 1945 Wiley-Liss, Inc.