Enhancement of indoleamine 2,3-dioxygenase activity in cancer patients receiving interferon-beta Ser.

Degradation of tryptophan to kynurenine, catalyzed by indoleamine 2,3-dioxygenase (IDO), has been shown previously to be augmented in human peripheral blood mononuclear cells (PBMCs) treated in vitro with interferons-alpha, -beta, and -gamma (IFNs), and in human epithelial cells treated with IFN-gamma. To determine whether administration of IFN in vivo also induced IDO activity, tryptophan degradation by PBMCs purified from patients was measured. PBMCs, obtained prior to and 24 h after i.v. bolus injection of 90 X 10(6) units or 180 X 10(6) units of IFN-beta Ser, were cultivated in medium containing [3H]tryptophan. After 48 h incubation, culture supernatants were harvested, and the amount of tryptophan degraded was measured by fractionation with high-performance liquid chromatography and quantification of radioactivity in resultant fractions. Significantly enhanced IDO activity was observed after IFN-beta Ser treatment, with a mean paired increase of 43% of maximum inducible activity. Thus, measurement of in vivo induction of IDO activity may be a useful indicator in optimizing therapeutic use of IFNs in neoplastic, infectious, and other clinical disorders.