Related Experiment Video
Updated: Sep 28, 2026
Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis
Published on: September 9, 2022
Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors
Gwen S Scott1, Sergei V Spitsin, Rhonda B Kean
1Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Abstract:
Uric acid (UA) is a purine metabolite that selectively inhibits peroxynitrite-mediated reactions implicated in the pathogenesis of multiple sclerosis (MS) and other neurodegenerative diseases. Serum UA levels are inversely associated with the incidence of MS in humans because MS patients have low serum UA levels and individuals with hyperuricemia (gout) rarely develop the disease. Moreover, the administration of UA is therapeutic in experimental allergic encephalomyelitis (EAE), an animal model of MS. Thus, raising serum UA levels in MS patients, by oral administration of a UA precursor such as inosine, may have therapeutic value. We have assessed the effects of inosine, as well as inosinic acid, on parameters relevant to the chemical reactivity of peroxynitrite and the pathogenesis of EAE. Both had no effect on chemical reactions associated with peroxynitrite, such as tyrosine nitration, or on the activation of inflammatory cells in vitro. Moreover, when mice treated with the urate oxidase inhibitor potassium oxonate were fed inosine or inosinic acid, serum UA levels were elevated markedly for a period of hours, whereas only a minor, transient increase in serum inosine was detected. Administration of inosinic acid suppressed the appearance of clinical signs of EAE and promoted recovery from ongoing disease. The therapeutic effect on animals with active EAE was associated with increased UA, but not inosine, levels in CNS tissue. We, therefore, conclude that the mode of action of inosine and inosinic acid in EAE is via their metabolism to UA.
Insights
Uric acid (UA) shows therapeutic potential for multiple sclerosis (MS) by inhibiting damaging reactions. Oral administration of UA precursors like inosinic acid effectively increased UA levels and treated experimental allergic encephalomyelitis (EAE) in mice.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Uric acid (UA) is a metabolite that inhibits peroxynitrite-mediated reactions, potentially impacting neurodegenerative diseases like multiple sclerosis (MS).
- Low serum UA levels are observed in MS patients, and hyperuricemia is associated with a lower incidence of MS.
- UA administration demonstrates therapeutic effects in experimental allergic encephalomyelitis (EAE), an animal model for MS.
Purpose of the Study:
- To assess the therapeutic potential of UA precursors, inosine and inosinic acid, in managing MS pathogenesis.
- To investigate the effects of inosine and inosinic acid on peroxynitrite reactivity and EAE.
- To determine if oral administration of UA precursors can increase serum UA levels and exert therapeutic effects.
Main Methods:
- In vitro assessment of inosine and inosinic acid on peroxynitrite-related chemical reactions and inflammatory cell activation.
- In vivo studies using mice treated with a urate oxidase inhibitor (potassium oxonate) and administered inosine or inosinic acid.
- Evaluation of clinical signs of EAE and UA/inosine levels in serum and CNS tissue.
Main Results:
- Inosine and inosinic acid did not affect peroxynitrite-mediated reactions or inflammatory cell activation in vitro.
- Oral administration of inosine or inosinic acid, combined with potassium oxonate, significantly elevated serum UA levels in mice.
- Inosinic acid administration suppressed clinical signs of EAE and promoted recovery, with therapeutic effects linked to increased CNS UA levels.
Conclusions:
- The therapeutic effects of inosine and inosinic acid in EAE are mediated through their metabolism to uric acid (UA).
- Increasing UA levels via precursor administration may represent a viable therapeutic strategy for MS and other neurodegenerative conditions.
