Anti-inflammatory effects of glucosamine in regulating the development of experimental autoimmune encephalomyelitis (EAE) (96.6)

Abstract

Abstract We attempted to understand the anti-inflammatory regulation of glucosamine-6-phosphate (GS-6-P) and glucosamine-6-sulfate (GS-6-S) in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Clinical symptoms in MOG35-55-induced EAE mice significantly decreased following either oral administration or intravenous injection of GS-6-P, whereas only intravenous injection of GS-6-S inhibited EAE development. After clinical symptoms of EAE were induced, intravenous injection of both GS-6-P and GS-6-S could alleviate EAE in mice although GS-6-P was more potent. Further analysis showed that both GS-6-P and GS-6-S dramatically inhibited lymphocytic infiltration in the brain and spinal cord, recovered IL-10 producing cells to a normal level, and significantly decreased total number of splenocytes, CD4 T cell populations, IFN-γ producing cells and Th17 cells in mice. Besides, both GS-6-P and GS-6-S significantly inhibited the gene expression of IL-12, T-bet and IFN-γ, suggesting that glucosamine suppressed Th1 CD4 T cell differentiation and thus blocked EAE. GS-6-P also significantly increased IL-4 producing cells in spleen, but GS-6-S did not, suggesting GS-6-P could also promote Th2 CD4 T cell differentiation and thus further inhibited EAE. Our results suggested that GS-6-P could be a new therapeutic drug for MS treatment. (Supported in part by NIH grants R01AI053703, R01ES09098, R01 AI058300, R01DA016545, R01HL058641, ES 019313 and P01AT003961).