ADMINISTRATION OF TUMOR-NECROSIS-FACTOR-ALPHA RESULTS IN A DECREASED PLACENTAL-TRANSFER OF AMINO-ACIDS IN THE RAT

The administration of an acute tumor necrosis factor-alpha (TNF) dose (100 mu g/kg BW) to 20-day pregnant rats resulted in a substantial dec rease in the fetal availability of maternally administered amino acids , as measured by the accumulation of alpha-amino-[1-C-14]isobutyrate ( [C-14]AIB) and [1-C-14]cycloleucine ([C-14]CLEU), nonmetabolizable ana logs of the amino acids alanine and leucine, respectively. Thus, TNF t reatment resulted in a decreased accumulation of the tracers in the wh ole fetus as well as in fetal liver. The cytokine also caused importan t changes on the maternal liver, where it increased both [C-14]AIB and [C-14]CLEU accumulation. In skeletal muscle and heart, TNF treatment resulted in decreased [C-14]AIB accumulation, but increased [C-14]CLEU . These changes in tissue amino acid uptake were accompanied by change s in circulating amino acids. TNF treatment promoted an increase in th e concentrations of both alanine and leucine in the maternal circulati on, whereas no changes in the circulating concentrations of these amin o acids were observed in the fetuses. The decreased fetal accumulation of maternally derived amino acid analogs is partially explained by a decrease in fetal blood flow [as measured by the accumulation of 14]1, 1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] induced by the cytokine) . It is suggested that the cytokine may be involved in fetal growth im pairment during pathological states (such as tumor growth or chronic i nfection) by promoting a decreased transplacental passage of amino aci ds, essential compounds for both protein accretion and oxidation in fe tal metabolism.