Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits

Abstract

A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions.

Short-term effects of tumor necrosis factor on energy and substrate metabolism in dogs.

“…Increased glucose production and utilization are major features of the metabolic response to the infection ( 1,2,50). Previous studies demonstrated that administration of TNF causes hypoglycemia (51 ), and this finding has been partially explained by the fact that TNF increases glucose utilization both in vitro (52,53) and in vivo (51,54,55), although there are conflicting results (56). The most striking aspect of the response to TNF in our study is the similarity to the response to glucagon infusion.…”

Effect of hydration status on cerebral blood flow and cerebrospinal fluid lactic acidosis in rabbits with experimental meningitis.

“…Possible explanations for this would include focal areas of ischemia that have been documented to occur in meningitis (29) but that would not be detected by measurement of total organ blood flow or humoral factors that would work in concert with ischemia to induce anaerobic metabolism. In other tissues, anaerobic glycolysis has been shown to be accelerated by humoral factors, including cytokines, resulting in increased glucose utilization and lactate production (30). This may be particularly relevant to the central nervous system in meningitis, where elevated cytokine levels have been measured in CSF and been found to be associated with poor outcome (13,17).…”

Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli.

“…Tumor necrosis factor (TNF)' and IL-I induce hemodynamic shock in experimental animals (1)(2)(3)(4); the combined infusion of IL-I and TNF produces tissue damage and metabolic derangements similar to those associated with injury and sepsis in humans (3)(4)(5). Furthermore, serum TNF and IL-1,8 levels are elevated in patients with Gram-negative bacteremia, and correlate with severity ofthe sepsis (6).…”

“…The Figure 7. Serum LPS levels after infusion of either saline, heat-killed S. epidermidis, 1 X 10"/kg, or heat-killed E. coli, 5.0 x 109/kg.…”