Experimental Allergic Encephalomyelitis

Abstract

During multiple sclerosis (MS) multifocal inflammation occurs in the central nervous system (CNS). Perivascular areas around small venules are infiltrated by T cells and macrophages. Myelin sheaths are damaged in these lesion areas which is considered to be a result from aberrant immune responses to myelin associated self-antigens. The role of these infiltrating macrophages, which in active lesions of MS outnumber the lymphocytes a 20-fold (1), is not clear. Since macrophages in the lesion areas have been described to be laden with myelin, their function is sometimes considered to be restricted to phagocytosis of damaged myelin which has been teared off the axons. However, since macrophages appear early in the lesion they could also act as effector cells, initiating and mediating tissue damage and myelin destruction. Activated macrophages secrete pro-inflammatory molecules like interleukin (IL)-lβ, IL-6, TNF-a, proteases and reactive oxygen species (ROS). Both TNF α and ROS have been described to degrade myelin in vitro (2,3), and inhibitors of IL-lβ, proteases, TNF α and ROS suppress neurological symptoms of an animal model for MS, experimental allergic encephalomyelitis (EAE)(4–6). Also in the CNS of rats with EAE macrophages are dominantly present (7). To study the role of these macrophages in the pathogenesis of EAE two different experimental approaches were used. Firstly, macro-phages were depleted from the circulation using a liposome-mediated technique during a T cell line-induced acute form of EAE as well as during a chronic relapsing form of EAE (CR-EAE) (8,9). To evaluate the effect of the macrophage depletion technique on microglia cells during EAE, liposomes were used in bone marrow chimeras (10,11). Secondly, migration of macrophages into the CNS during EAE was inhibited by blockade of the aMβ2 integrin, also named complement receptor type 3 (CR3)(12).