Regulation of b-Chemokine mRNA Expression in Adult Rat Astrocytes by Lipopolysaccharide, Proinflammatory and Immunoregulatory Cytokines. Scand J Immunol 1998;48:502-508 Astrocytes constitute a part of the blood-brain barrier. Chemokine expression by astrocytes may contribute to leucocyte infiltration within the central nervous system (CNS) during inflammation. To investigate factor(s) regulating chemokine expression by astrocytes, we studied the induction of b-chemokine mRNA expression in adult rat astrocytes. Astrocyte-derived monocyte chemoattractant protein-1 (MCP-1), RANTES, macrophage inflammatory protein (MIP)-1a and MIP-1b mRNA were induced by interferon-g (IFN-g). Tumour necrosis factor-a (TNF-a) induced MCP-1, RANTES and MIP-1b mRNA expression, and lipopolysaccharide (LPS) induced MCP-1, MIP-1a and MIP-1b mRNA expression in astrocytes. LPS-induced MCP-1, MIP-1a and MIP-1b mRNA expression by astrocytes was antagonized by transforming growth factor (TGF)-b1 and interleukin (IL)-10. TGF-b1 and IL-10 also down-regulated MCP-1 and RANTES mRNA expression induced by TNF-a. IL-10, but not TGF-b1, inhibited MIP-1b mRNA expression induced by TNF-a. The results of this in vitro study suggest that b-chemokine mRNA expression by adult rat astrocytes can be induced by LPS or proinflammatory cytokines, while regulatory cytokines, such as TGF-b1 and IL-10, down-regulate astrocytederived b-family chemokine mRNA expression induced by LPS, IFN-g and TNF-a. Further study of CNS chemokines will enhance our understanding of leucocyte recruitment to the CNS and suggest therapeutic strategies for neurological disorders.

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.