[Uric acid and multiple sclerosis].
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE. Epidemiological studies have shown that MS and gout are almost mutually exclusive diseases. Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission. Inosine, a uric acid precursor, can be used to raise uric acid levels in serum and may provide some benefit in MS patients. A small study of ten patients with progressive MS has demonstrated some improved function in three of them and no sign of progression or relapse in the other. However, this study does not justify a recommendation for use of inosine in MS patients yet. At present, uric acid can solely be regarded as a marker of disease activity in MS. In addition, the current knowledge of uric acid and MS supports hypotheses which predict a positive effect of radical scavengers in MS.
Mattle
H P
HP
Neurologische Klinik und Poliklinik, Universitätsspital Bern, Inselspital, Bern.
Lienert
C
C
Greeve
I
I
D015415:Biomarkers / Q000097:blood; D016166:Free Radical Scavengers / Q000097:blood*; D006801:Humans; D007288:Inosine / Q000502:physiology / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control*; D012016:Reference Values; D014527:Uric Acid / Q000097:blood*
D015415:Biomarkers; D016166:Free Radical Scavengers; D014527:Uric Acid; D007288:Inosine