Attenuation of experimental autoimmune demyelination in complement-deficient mice

The exact mechanisms leading to CNS inflammation and myelin destruction in multiple sclerosis and in its animal model, experimental allergic encephalo myelitis (EAE) remain equivocal. In both multiple sclerosis and EAE, comple ment activation is thought to play a pivotal role by recruiting inflammator y cells, increasing myelin phagocytosis by macrophages, and exerting direct cytotoxic effects through the deposition of the membrane attack complex on oligodendrocytes, Despite this assumption, attempts to evaluate complement 's contribution to autoimmune demyelination in vivo have been limited by th e lack of nontoxic and/or nonimmunogenic complement inhibitors. In this rep ort, we used mice deficient in either C3 or factor B to clarify the role of the complement system in an Ah-independent model of EAE, Both types of com plement-deficient mice presented with a markedly reduced disease severity, Although induction of EAE led to inflammatory changes in the meninges and p erivascular spaces of both wild-type and complement-deficient animals, in b oth C3(-/-) and factor B-/- mice there was little infiltration of the paren chyma by macrophages and T cells. In addition, compared with their wild-typ e littermates, the CNS of both C3(-/-) and factor B-/- mice induced for EAE are protected from demyelination, These results suggest that complement mi ght be a target for the therapeutic treatment of inflammatory demyelinating diseases of the CNS.