Longitudinal study of tryptophan degradation during and after pregnancy

In mice, activation of indoleamine-2,3-dioxygenase (IDO), an enzyme converting tryptophan to N-formyl-kynurenine, was found to be necessary requirement to achieve immunotolerance against the fetus and thus uncomplicated pregnancy. In plasma from 20 healthy pregnant women with singleton pregnancies we consecutively analyzed kynurenine and tryptophan concentrations during pregnancy (1 specimen at each trimester of gestation) and postpartum (week 6). None of the women had any signs of infection at the time of plasma sampling, but the study population was otherwise unselected. The kynurenine to tryptophan ratio (kyn/trp) was calculated as an estimate of IDO activity, and data were compared to concentrations of neopterin and 55kD soluble tumor necrosis factor receptor (sTNF-R55), two indicators of immune activation, and to alanineaminotransferase (ALT) levels. Increasing kynurenine and decreasing tryptophan concentrations were found during pregnancy, data suggesting significant degradation of tryptophan. In parallel, increasing concentrations of immune activation markers neopterin and sTNF-R55 were observed, correlating significantly to kyn/trp. The data point to an involvement of cytokine-induced IDO activation in the degradation of tryptophan observed during pregnancy. After pregnancy, sTNF-R55 and also neopterin concentrations declined, whereas tryptophan concentrations increased, indicating that immune activation and activation-induced tryptophan degradation returned to baseline. By contrast, still increased kynurenine concentrations and also increased kyn/trp point to continuing catabolism of tryptophan. Postpartum elevation of liver enzyme ALT may suggest that increased activity of hepatic tryptophan pyrrolase could be involved in increased conversion of tryptophan despite low degree of immune activation. We conclude that IDO is activated in pregnancy and that the decrease of tryptophan might be related to immune activation phenomena. Sustained increase of kynurenine postpartum seems independent from immune activation process.