Different roles of IL-1 and TNF on hemodynamics and interorgan amino acid metabolism in awake dogs

The present study examines the effects of interleukin 1 (IL-1) and tumor necrosis factor (TNF) on various hemodynamic parameters and interorgan fluxes of amino acids, glucose, and lactate in chronically catheterized awake dogs. The dogs received 5 micrograms.kg-1.h-1 of either human recombinant IL-1 beta or TNF intravenously for 2 h. Hemodynamic parameters and substrate fluxes across the gut and liver were determined during and 2 h after discontinuation of the cytokine infusions. Substrate fluxes were calculated by blood flows and arteriovenous differences. Both IL-1 and TNF enhanced the uptake of alanine, uptake of lactate, and output of glucose by the liver. These changes were associated with elevated arterial levels of alanine and lactate while arterial levels of glucose decreased. Uptake of glutamine by the liver was reduced by either IL-1 or TNF infusions. The effects of IL-1 and TNF on the hemodynamic parameters and on gut amino acid metabolism varied with the cytokine infused. IL-1 produced hyperdynamic state, increased splanchnic blood flow, and enhanced glutamine uptake by the gut. TNF infusion did not cause a hyperdynamic state, nor did it alter the gut handling of amino acids. We conclude that IL-1 and TNF exert distinct different effects on the systemic and hemodynamic parameters and on interorgan balances of amino acids, glucose, and lactate across the gut and the liver.