Independent and combined actions of interleukin-1 beta, tumor necrosis factor alpha, and glucagon on amino acid metabolism in the isolated perfused rat liver.
Conflicting reports concerning the hepatic effects of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) in the metabolic response to injury led us to investigate the influence of physiological concentrations of these cytokines on amino acid metabolism in the isolated perfused rat liver. IL-1 beta was ineffective at a concentration of 1 ng/mL, whereas TNF alpha (0.7 ng/mL) reduced the uptake of some of the main gluconeogenic amino acids (alanine, -55.3 +/- 4.9 v -72.9 +/- 13.7 nmol.min-1.g-1 in controls, P < .05) without affecting urea synthesis. TNF alpha increased glucose uptake by 237% and inhibited that of free fatty acids (-1.6 +/- 1.4 v -9.9 +/- 6.7 nmol.min-1.g-1 in controls, P < .05). IL-1 beta and TNF alpha potentiated glucagon-induced total amino acid uptake by 56% and 87%, respectively. They also affected glucagon-activated gluconeogenesis, leading to an initial potentiation of glucose release. Thereafter, IL-1 beta inhibited glucagon action, leading to an hepatic uptake of glucose. These results indicate that (1) in the conditions of the study, IL-1 beta has no direct effect on hepatic amino acid exchanges and utilization; (2) TNF alpha which exerted an inhibitory effect on these parameters, could be involved in the reduced amino acid exchanges during the end stage of sepsis; (3) the TNF alpha-induced increase in glucose uptake could be related to an inhibition of gluconeogenesis and/or to the activation of glucose utilization by Kupffer cells; (4) IL-1 beta and TNF alpha both potentiate the action of glucagon on hepatic amino acid uptake and utilization; and (5) complex interactions between Kupffer cells and hepatocytes on the one hand and between cytokines and hormones on the other hand could account for the differences in hepatic metabolism according to the stage of the response to injury.
Laboratoire de Biochimie, Hôpital Saint Antoine, Paris, France.
J P
JP
De Bandt
S K
SK
Lim
F
F
Plassart
C C
CC
Lucas
C
C
Rey
R
R
Poupon
J
J
Giboudeau
L
L
Cynober
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D005934:Glucagon / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000596:Amino Acids; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005934:Glucagon