Comparative effects of tumour necrosis factor-alpha (cachectin), interleukin-1-beta and tumour growth on amino acid metabolism in the rat in vivo. Absorption and tissue uptake of alpha-amino[1-14C]isobutyrate.

Abstract

The effects of acute administration of either tumour necrosis factor-alpha (cachectin) (TNF) or interleukin-1-beta (IL-1), or of tumour growth (Walker-256 carcinosarcoma), on blood amino acid concentrations and tissue alpha-amino[1-14C]isobutyrate (AIB) uptake in virgin and lactating rats were compared. Both monokines decreased the blood concentrations of those amino acids (serine, glycine, alanine and proline) transported via the A system. Tumour growth decreased the blood concentrations of serine, proline and histidine, whereas the concentrations of glutamine and leucine were increased. IL-1 decreased the intestinal absorption of AIB in all groups studied; TNF or tumour growth had no effect. Tissue AIB uptake was increased (1.5-2.5-fold) in liver, whereas it was decreased in heart and skeletal muscle of the three treatment groups (except skeletal muscle of the IL-1-treated rats). Lactating rats had lower hepatic uptake of AIB compared with livers of virgin rats. IL-1 increased the hepatic uptake of AIB in lactating rats, but not to the values seen in virgin rats treated with IL-1; there was no effect of the cytokine on muscle or mammary-gland uptake. In adrenalectomized rats, the stimulatory effect of IL-1 on hepatic AIB uptake was diminished, whereas that of TNF still persisted. IL-1 caused a marked decrease of AIB uptake in muscle and heart of adrenalectomized rats, which was accompanied by an increase in the blood concentrations of branched-chain amino acids. These effects did not occur with TNF. It is concluded that the effects of the cytokines on tissue amino acid metabolism may depend on a differential endocrine response involving glucagon and/or glucocorticoids.