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.
Carlin
J M
JM
Department of Medical Microbiology, University of Wisconsin Medical School, Madison 53706.
Borden
E C
EC
Byrne
G I
GI
D004334:Drug Administration Schedule; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007370:Interferon Type I / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D009369:Neoplasms / Q000628:therapy*; D010105:Oxygenases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism; D014366:Tryptophan Oxygenase
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007370:Interferon Type I; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D014364:Tryptophan; D010105:Oxygenases; D014366:Tryptophan Oxygenase; D000068556:Interferon beta-1a