Background Urate is a natural antioxidant and may prevent CNS tissue damage and the clinical manifestations of experimental autoimmune encephalitis. Results from clinical studies are conflicting and the contribution of urate to the pathogenesis of Multiple Sclerosis (MS) remains uncertain. Objective To evaluate serum urate levels in MS patients and their relationships with clinical, demographic and MRI variables. Methods Levels of non-fasting serum uric acid and creatinine were determined by an automated enzymatic assay and glomerular filtration rate was assessed in 245 MS patients, in 252 age/sex-matched neurological controls (NC) and in 59 Healthy controls (HC). Results Median serum urate levels did not differ between MS patients (3.8 mg/dL), HC (4.0 mg/dl) and NC (4.0 mg/dL). Serum urate levels were lower in females than in males in all groups (p = <0.0001). In female-MS, serum urate levels (3.2 mg/dL) were lower compared to those in female HC (3.8; p = 0.01) and NC (3.5 mg/dL; p = 0.02), whereas in male-MS they(4.8 mg/dL) did not differ from those in male HC (4.5 mg/dl) and NC (4.8 mg/dL). Urate concentrations trended to be lower in Clinically isolated syndromes suggestive of MS (3.7 mg/dL) and in relapsing MS (3.7 mg/dL), compared to patients with progressive MS (4.4 mg/dL; p = 0.06), and in patients with an annual relapse rate (ARR) >2 (3.3 mg/dL) than in those with an ARR ≤2: 3.9 mg/dL; p = 0.05). Significant lower serum urate levels were found in females than in males in all clinical MS subtypes (p<0.01), separately evaluated. Female sex (beta: ？0.53; p<0.00001) was the most significant determinant of serum urate concentrations in MS patients on multivariate regression analysis. Conclusions Our findings suggest that low urate levels could be of significance in predominantly inflammatory phases of MS even at the early stage and mainly in females.
Ames BN, Cathcart R, Schwiers E, Hochstein P (1988) Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA. 78: 6858–6862.
Hooper DC, Spitsin S, Kean RB, Champion JM, Dickson GM, et al. (1998) Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci U S A 95: 675–680.
Becker BF, Kastenbauer S, K？del U, Kiesl D, Pfister HW (2004) Urate oxidation in CSF and blood of patients with inflammatory disorders of the nervous system. Nucleosides Nucleotides Nucleic Acids 23: 1201–1204.
Gonsette RE, Sindic C, D’hooghe MB, De Deyn PP, Medaer R, et al. (2010) Boosting endogenous neuroprotection in multiple sclerosis: the Association of Inosine and Interferon beta in relapsing- remitting Multiple Sclerosis (ASIIMS) trial. Mult Scler 16: 455–462.