Monocyte chemoattractant protein-1 enhances HSV-induced encephalomyelitis by stimulating Th2 responses

Monocyte chemoattractant protein (MCP)-1 has a pathogenic role in herpesvir us-induced encephalomyelitis (HSM). Anti-MCP-1 antibody greatly decreased H SM severity in mice infected with herpes simplex virus type 2 (HSM mice), c ompared with its effect in control HSM mice treated with rabbit immunoglobu lin. HSM severity was markedly enhanced in mice previously treated with a m ixture of interleukin (IL) 4 and -10. In response to stimulation with antig en, HSM mouse cells isolated from cerebrospinal fluids (CSF cells) produced IL-4 in culture fluids; however, IL-4 production decreased in CSF cells de rived from HSM mice previously treated with anti-MCP-1 antibody. A macropha ge population isolated in CSF cells from HSM mice (CSF-M phi) produced MCP- 1 in culture fluids. In response to stimulation with herpesvirus antigen, a population of T cells isolated from CSF cells from HSM mice (CSF-T cells) produced IL-4 into their culture fluids, although MCP-1 was not produced by CSF-T cells stimulated by this antigen. IL-4 production by CSF-T cells was markedly enhanced when they were stimulated with viral antigen in the pres ence of murine recombinant MCP-1 (rMCP-1). Furthermore, IL-4 was produced i n naive splenic T cells cocultured with CSF-M phi. These results indicate t hat the severity of HSM is influenced by MCP-1, which stimulates Th2 respon ses.