AJP - Endocrinology and Metabolism, Vol 268, Issue 2 E255-E261, Copyright © 1995 by American Physiological Society
Differential effects of interleukin-1 receptor antagonist in cytokine- and endotoxin-treated rats
P. R. Ling, N. W. Istfan, E. Colon and B. R. Bistrian
Laboratory of Nutrition/Infection, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Previous studies have demonstrated that the administration of the
cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF)(20
micrograms/kg) to rats in a fasting state can produce many and perhaps most
of the metabolic alterations found in patients with sepsis and injury. The
purposes of the present study were 1) to define the metabolic effects of
IL-1 and TNF during a fed state provided by continuous intravenous feeding
for 20 h and 2) to characterize the unique effects of IL-1 among the
overall response to cytokines by using IL-1 receptor antagonist (IL-1RA; 5
mg/kg). The effects were also explored during the endotoxemic condition
induced by infusion of 200 micrograms/kg of endotoxin into rats. The
results showed that during feeding IL-1 is responsible for the increase in
glucose flux and plasma insulin, the development of insulin resistance, and
plasma zinc depression during condition mimicking sepsis and injury,
similar to effects observed in the fasting state. The changes in energy
expenditure have a more complex mechanism. The results also suggested that
certain host responses to cytokines or endotoxin, particularly related to
protein metabolism, differed between the fed and fasting states. These data
may have a special clinical relevance for the insulin-resistant state that
develops during severe infection, since using IL-1RA in conjunction with
nutritional therapy may offer additional advantages in the treatment of
these severe metabolic disorders.
