Tryptophan degradation during and after gestation

In mice, activation of indoleamine-(2,3)-dioxygenase (IDO), an enzyme converting tryptophan to N-formyl-kynurenine, is required to achieve immunotolerance against the fetus and thus uncomplicated pregnancy. On the other hand, postpartum blues and depression appear to be related to reduced availability of tryptophan and serotonin. In healthy pregnant women with singleton pregnancies we consecutively analyzed kynurenine and tryptophan concentrations during pregnancy and postpartum. 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, two indicators of immune activation, and to alanineaminotransferase (ALT) levels. Increasing kynurenine and decreasing tryptophan concentrations were found during pregnancy. The data confirm earlier results and suggest significant degradation of tryptophan. In parallel, increasing concentrations of immune activation markers neopterin and sTNF-R55 were found, correlating significantly to the 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 has ceased. By contrast, still increased kynurenine concentrations and also increased kyn/trp suggest continuing turnover of tryptophan. Because also ALT was increased postpartum, abnormal activity of hepatic tryptophan pyrrolase and possibly other enzymes could be involved. We conclude that the decrease of tryptophan during pregnancy might be related to immune activation phenomena. Sustained increase of kynurenine postpartum seems independent from immune activation process, rather it seems related to abnormal activity of liver enzymes.