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The Journal of Neuroscience, September 15, 2001, 21(18):7046-7052

Interleukin-1beta Promotes Repair of the CNS

Jeffrey L. Mason1, Kinuko Suzuki2, David D. Chaplin4, and Glenn K. Matsushima1, 3

1 Curriculum in Neurobiology and the University of North Carolina Neuroscience Center, 2 Department of Pathology and Laboratory Medicine, and 3 Department of Microbiology and Immunology, and the Program of Molecular Biology and Biotechnology, University of North Carolina, Chapel Hill, North Carolina 27599, and 4 Department of Internal Medicine and Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110

Interleukin-1beta (IL-1beta ) is a proinflammatory cytokine associated with the pathophysiology of demyelinating disorders such as multiple sclerosis and viral infections of the CNS. However, we demonstrate here that IL-1beta appears to promote remyelination in the adult CNS. In IL-1beta -/- mice, acute demyelination progressed similarly to wild-type mice and showed parallel mature oligodendrocyte depletion, microglia-macrophage accumulation, and the appearance of oligodendrocyte precursors. In contrast, IL-1beta -/- mice failed to remyelinate properly, and this appeared to correlate with a lack of insulin-like growth factor-1 (IGF-1) production by microglia-macrophages and astrocytes and to a profound delay of precursors to differentiate into mature oligodendrocytes. Thus, IL-1beta may be crucial to the repair of the CNS, presumably through the induction of astrocyte and microglia-macrophage-derived IGF-1.

Key words: oligodendrocytes; astrocytes; microglia; remyelination; cytokines; growth factors


Copyright © 2001 Society for Neuroscience  0270-6474/01/21187046-07$05.00/0


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