Neopterin and Oxidation Products in the Blood of Patients with Various Forms of Dementia

Abstract

Human monocyte-derived macrophages and dendritic cells produce increased amounts of neopterin derivatives upon stimulation with interferon-γ (IFN-γ). In parallel, such stimulated cells release a record of oxidizing specics as part of their cytocidal repertoire. Production of reactive oxygen species by stimulated immunocompetent cells may be the reason for the depletion of antioxidant vitamins and the development of oxidative stress during diseases with stimulated immune system. Noteworthy also neopterin derivatives are able to interfere with reactive oxygen, chlorine, and nitrogen species, and neopterin itself could contribute to oxidative stress. In vivo, neopterin concentrations thus allow not only to monitor cell-mediated immune response, they also allow to estimate the extent of oxidative stress which emerges during immune response. In certain diseases associations between higher neopterin levels and markers of oxidative stress have been reported. In neurodegenerative diseases, neopterin concentrations in scrum and cerebrospinal fluid also correlate with the cognitive decline in patients. In this studv we compared serum concentrations of neopterin with serum concentrations of peroxides and homocysteine in patients with various forms of dementia and in 5 healthy elderly controls. In patients of either form of dementia serum concentrations of peroxides and neopterin were increased compared to controls. There existed a positive correlation between age and concentrations of peroxides, neopterin and homocysteine. The data further supportile view that increased neopterin concentrations are associated with oxidative stress which could underlie c¡r increased demand of antioxidants in neurodegenerative disorders. It appears important that such changes can h> detected in the blood of patients with dementia, albeit its pathogenesis is considered to be confined to the brain The results further suggest that aging is associated with immune system activation which may lead to the increased production of peroxides.

Keywords

• dementia
• neopterin
• peroxides
• oxidative stress
• homocysteine