Suppression of Experimental Autoimmune Encephalomyelitis in Mice by -Hydroxy -Methylbutyrate, a Body-Building Supplement in Humans

Although several immunomodulatory drugs are available for multiple sclerosis (MS), most present significant side effects with long-term use. Therefore, delineation of nontoxic drugs for MS is an important area of research. beta-Hydroxy beta-methylbutyrate (HMB) is accessible in local GNC stores as a muscle-building supplement in humans. This study underlines the importance of HMB in suppressing clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of MS. Dose-dependent study shows that oral HMB at a dose of 1 mg/kg body weight/d or higher significantly suppresses clinical symptoms of EAE in mice. Accordingly, orally administered HMB attenuated perivascular cuffing, preserved the integrity of the blood similar to brain barrier and blood similar to spinal cord barrier, inhibited inflammation, maintained the expression of myelin genes, and blocked demyelination in the spinal cord of EAE mice. From the immunomodulatory side, HMB protected regulatory T cells and suppressed Th1 and Th17 biasness. Using peroxisome proliferator-activated receptor (PPAR)alpha(-/-) and PPAR beta(-/-) mice, we observed that HMB required PPAR beta, but not PPAR alpha, to exhibit immunomodulation and suppress EAE. Interestingly, HMB reduced the production of NO via PPAR beta to protect regulatory T cells. These results describe a novel anti-autoimmune property of HMB that may be beneficial in the treatment of MS and other autoimmune disorders.