title: Hyperhomocysteinemia and immune activation.
abstract: Hyperhomocysteinemia is an established risk factor for atherosclerosis, thrombosis and other vascular diseases. Homocysteine auto-oxidation is considered to be crucially involved in the pathogenesis of these diseases. However, the question remains to be elucidated whether vitamin deficiency and homocysteine accumulation are causal for disease development or rather comprise a secondary phenomenon. Most diseases accompanied by hyperhomocysteinemia are also associated with ongoing activation of the immune system. In vitro experiments show homocysteine to accumulate in stimulated peripheral blood mononuclear cells. In patients with coronary heart disease, with rheumatoid arthritis and in patients with dementia, an association between cellular immune activation and homocysteine metabolism is found. Homocysteine concentrations not only correlate inversely with folate concentrations, they also show a positive relationship with concentrations of immune activation markers like neopterin. Moreover, in patients with various kinds of dementia, increased concentrations of serum peroxides, homocysteine and neopterin correlate with each other. Studies support a role of immune system activation in the development of hyperhomocysteinemia. Stimulation and proliferation of immune cells may lead to the production of reactive oxygen species that may oxidize antioxidants and oxidation-sensitive B-vitamins. An enhanced demand for antioxidants as well as folate and vitamin B12 may develop, together with hyperhomocysteinemia, despite sufficient dietary intake.
authors.affiliation: Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schroecksnadel
authors.forename: Barbara
authors.initials: B
authors.lastname: Frick
authors.forename: Christiana
authors.initials: C
authors.lastname: Winkler
authors.forename: Friedrich
authors.initials: F
authors.lastname: Leblhuber
authors.forename: Barbara
authors.initials: B
authors.lastname: Wirleitner
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
mesh_terms: D016207:Cytokines / Q000097:blood / Q000276:immunology; D003704:Dementia / Q000097:blood / Q000150:complications / Q000276:immunology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000097:blood / Q000276:immunology; D014652:Vascular Diseases / Q000097:blood / Q000150:complications / Q000276:immunology
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D006710:Homocysteine