Plasma Homocysteine and Immune Activation in Patients with Malignant Melanoma Undergoing Treatment with IFN-α

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-α(IFN-α) 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-α to activate macrophages. Plasma concentrations of homocysteine, folate, and vitamin B₁₂ were determined in 15 patients with malignant melanoma during 12 weeks of high-dose IFN-α 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-α did not differ from baseline. In contrast, significant increases in neopterin formation and tryptophan degradation were apparent during IFN-α therapy. Plasma concentrations of vitamin B₁₂ and cysteine also increased. These results indicate that IFN-α directly activates macrophages to release neopterin and to degrade tryptophan, but obviously treatment with INF-α did not affect homocysteine metabolism.