Plasma homocysteine and immune activation in patients with malignant melanoma undergoing treatment with IFN-α

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- a (IFNa) 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- a 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- a 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- a did not differ from baseline. In contrast, significant increases in neopterin formation and tryptophan degradation were apparent during IFN-a therapy. Plasma concentrations of vitamin B 12 and cysteine also increased. These results indicate that IFN-a directly activates macrophages to release neopterin and to degrade tryptophan, but obviously treatment with INF- a did not affect homocysteine metabolism.