Increased neopterin production and tryptophan degradation in advanced Parkinson’s disease

The cytokine interferon-c stimulates human monocytes/macrophages to release large amounts of neop-terin. Increased neopterin concentrations in body fluids of patients are observed during diseases with acti-vated cellular (TH1-type) immune response such as allograft rejection, virus infections, autoimmune disorders, or malignant tumors but also in neurodegenerative diseases or during pregnancy. In various cells interferon-c induces indoleamine 2,3-dioxygenase (IDO) which degrades tryptophan via the kynurenine pathway. Therefore like increased neopterin formation, enhanced tryptophan degradation is observed in diseases concomitant with cellular immune activation. Disturbed metabolism of tryptophan affects biosyn-thesis of neurotransmitter 5-hydroxytryptamine (serotonin), and it appears to be associatedwith an increased susceptibility for depression. In fact, enhanced neopterin concentrations together with increased degradation of tryptophan and low serum levels of tryptophan correlate with neuropsychiatric abnormalities like cog-nitive decline and depressive symptoms especially in long-lasting and chronic diseases. Activation of IDO could represent an important link between the immunological network and the pathogenesis of depression