title: Plasma homocysteine and immune activation in patients with malignant melanoma undergoing treatment with IFN-alpha.
abstract: Immune activation and cell proliferation may contribute to the development of increased homocysteine concentrations in patients with malignant diseases. In this study, we investigated the effect of interferon-alpha (IFN-alpha) on plasma homocysteine concentrations in patients being treated for malignant melanoma. In parallel, neopterin formation and tryptophan degradation were monitored to assess the capacity of IFN-alpha to activate macrophages. Plasma concentrations of homocysteine, folate, and vitamin B(12) were determined in 15 patients with malignant melanoma during 12 weeks of high-dose IFN-alpha therapy. Concurrently, concentrations of neopterin, tryptophan, and kynurenine were measured, and the kynurenine/tryptophan ratio (kyn/trp) was calculated. Homocysteine and folate concentrations during treatment with IFN-alpha did not differ from baseline. In contrast, significant increases in neopterin formation and tryptophan degradation were apparent during IFN-alpha therapy. Plasma concentrations of vitamin B(12) and cysteine also increased. These results indicate that IFN-alpha directly activates macrophages to release neopterin and to degrade tryptophan, but obviously treatment with INF-alpha did not affect homocysteine metabolism.
authors.affiliation: Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Frick
authors.forename: Lucile
authors.initials: L
authors.lastname: Capuron
authors.forename: Katharina
authors.initials: K
authors.lastname: Schröcksnadel
authors.forename: Dominique L
authors.initials: DL
authors.lastname: Musselman
authors.forename: David H
authors.initials: DH
authors.lastname: Lawson
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Miller
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007737:Kynurenine / Q000097:blood; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy*; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D014364:Tryptophan / Q000097:blood; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D006710:Homocysteine; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan; D005492:Folic Acid; D014805:Vitamin B 12