Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1α and monocyte chemotactic protein-1

Experimental autoimmune encephalomyelitis (EAE) is a T lymphocyte-mediated disease of the central nervous system (CNS), characterized by mononuclear cell infiltration and demyelination resulting in paralysis. We examined CC chemokine expression in the CNS throughout the entire course of the disease and found that the production of macrophage inflammatory protein (MIP)-1 alpha correlated with increasing acute disease severity and remained elevated throughout chronic, relapsing disease. In contrast, a substantial level of monocyte chemotactic protein (MCP)-1 expression was not observed until late in acute disease and continued to be evident in the relapsing phase of the disease. MCP-1 expression correlated with increasing severity of clinical relapses. Lower levels of RANTES in the CNS were noted throughout the disease course, but showed little correlation with either acute or relapsing disease. Although RANTES expression was observed during the entire course of disease, anti-RANTES treatment had no effect on clinical disease progression. Anti-MCP-l, but not anti-MIP-1 alpha, treatment during relapsing EAE decreased clinical severity of relapsing disease. Furthermore, anti-MCP-l treatment reduced CNS macrophage accumulation during relapsing EAE. These results suggest that MIP-1 alpha controls mononuclear cell accumulation during acute EAE, while MCP-1 controls mononuclear cell infiltration during relapsing EAE. (C) 1998 Elsevier Science B.V. All rights reserved.