Nasal administration of transforming growth factor-beta1 induces dendritic cells and inhibits protracted-relapsing experimental allergic encephalomyelitis.
Cytokines have a crucial role in initiation and perturbation of EAE that represents an animal model of multiple sclerosis (MS). Administration of transforming growth factor-beta1 (TGF-beta1) to EAE mice improves clinical EAE and prevents relapses by unknown mechanisms. Administering low doses of TGF-beta1 nasally, we confirmed that TGF-beta1 inhibited development and relapse of protracted-relapsing EAE (PR-EAE) in DA rats. Infiltration of CD4+ T-cells and macrophages within the central nervous system was clearly reduced, while proliferation and IFN-gamma secretion of mononuclear cells (MNC) was augmented in TGF-beta1-treated EAE rats compared to PBS-treated control EAE rats. TGF-beta1 administered nasally also increased nitric oxide production and CD4+ T cell apoptosis. TGF-beta1 treated rats showed augmented proliferation of dendritic cells (DC) compared to MNC. These data imply that low doses of TGF-beta1 given by the nasal route prevent PR-EAE and upregulate DC functions that may be involved for disease prevention.
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
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D000281:Administration, Intranasal; D000818:Animals; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D002455:Cell Division; D002478:Cells, Cultured; D003627:Data Interpretation, Statistical; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D007167:Immunotherapy; D008297:Male; D051379:Mice; D009103:Multiple Sclerosis / Q000628:therapy; D004676:Myelin Basic Protein / Q000008:administration & dosage; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D013154:Spleen / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D015854:Up-Regulation
D004676:Myelin Basic Protein; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide