Glucosamine abrogates the acute phase of experimental autoimmune encephalomyelitis by induction of Th2 response.
Glucosamine, a natural glucose derivative and an essential component of glycoproteins and proteoglycans, has been safely used to relieve osteoarthritis in humans. Recent studies have shown that glucosamine also possesses immunosuppressive properties and is effective in prolonging graft survival in mice. Whether this reagent is effective in human multiple sclerosis (MS), an inflammatory demyelination in the CNS, is not known. We thus investigated the therapeutic effect of glucosamine on experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We demonstrated that oral, i.p., or i.v. administration of glucosamine significantly suppressed acute EAE, with reduced CNS inflammation and demyelination. A significant, albeit not strong, blockade of Th1 response and an up-regulation of Th2 cytokines (IL-5 and IL-10) are observed in the splenocytes of glucosamine-treated mice. Glucosamine also regulates IL-5 and IL-10 in vitro. As glucosamine is able to effectively suppress acute EAE, has low or absent toxicity, and has been safely used in humans orally, our study suggests a potential use for this drug alone or in combination with other disease-modifying immunotherapies to enhance their efficacy and reduce their doses in MS and possibly other autoimmune disorders. Furthermore, because glucosamine functions not simply as an immunosuppressant, but as a mild immunomodulator, administration of glucosamine provides a novel immunoregulatory approach for autoimmune disorders.
Zhang
Guang-Xian
GX
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA. guang-xian.zhang@jefferson.edu
Yu
Shuo
S
Gran
Bruno
B
Rostami
Abdolmohamad
A
D000284:Administration, Oral; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005944:Glucosamine / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
D016207:Cytokines; D007166:Immunosuppressive Agents; D018992:Myelin-Associated Glycoprotein; D009569:Nitric Oxide; D005944:Glucosamine