Nasal administration of transforming growth factor-β1 induces dendritic cells and inhibits protracted-relapsing experimental allergic encephalomyelitis

Abstract

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-β1 (TGF-β1) to EAE mice improves clinical EAE and prevents relapses by unknown mechanisms. Administering low doses of TGF-β1 nasally, we confirmed that TGF-β1 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-g secretion of mononuclear cells (MNC) was augmented in TGF-β1-treated EAE rats compared to PBS-treated control EAE rats. TGF-β1 administered nasally also increased nitric oxide production and CD4+ T cell apoptosis. TGF-β1 treated rats showed augmented proliferation of dendritic cells (DC) compared to MNC. These data imply that low doses of TGF-β1 given by the nasal route prevent PR-EAE and upregulate DC functions that may be involved for disease prevention.

Keywords

transforming growth factor-β dendritic cell intranasal immunotherapy experimental allergic encephalomyelitis multiple sclerosis apoptosis

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