Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Differentiation / biosynthesis
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Astrocytes / metabolism
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Astrocytes / pathology
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Cell Count
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Central Nervous System / drug effects
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Central Nervous System / metabolism*
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Central Nervous System / pathology
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Chelating Agents
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Corpus Callosum / drug effects
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Corpus Callosum / metabolism
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Corpus Callosum / pathology
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Cuprizone
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Demyelinating Diseases / chemically induced
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Demyelinating Diseases / pathology
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Demyelinating Diseases / physiopathology*
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Disease Progression
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Glutathione S-Transferase pi
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Glutathione Transferase / biosynthesis
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Insulin-Like Growth Factor I / biosynthesis
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Insulin-Like Growth Factor I / genetics
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Interleukin-1 / genetics
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Interleukin-1 / metabolism*
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Interleukin-1 / pharmacology
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Isoenzymes / biosynthesis
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Macrophages / metabolism
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Macrophages / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microglia / metabolism
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Microglia / pathology
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Myelin Sheath / metabolism
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Oligodendroglia / drug effects
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Oligodendroglia / metabolism
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Oligodendroglia / pathology
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RNA, Messenger / metabolism
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Regeneration / drug effects
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Regeneration / physiology*
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Stem Cells / cytology
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Stem Cells / metabolism
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Up-Regulation / drug effects
Substances
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Antigens, Differentiation
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Chelating Agents
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Interleukin-1
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Isoenzymes
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RNA, Messenger
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Cuprizone
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Insulin-Like Growth Factor I
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Glutathione S-Transferase pi
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Glutathione Transferase
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Gstp1 protein, mouse