Interleukin-1beta promotes repair of the CNS

J Neurosci. 2001 Sep 15;21(18):7046-52. doi: 10.1523/JNEUROSCI.21-18-07046.2001.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Cell Count
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism*
  • Central Nervous System / pathology
  • Chelating Agents
  • Corpus Callosum / drug effects
  • Corpus Callosum / metabolism
  • Corpus Callosum / pathology
  • Cuprizone
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / physiopathology*
  • Disease Progression
  • Glutathione S-Transferase pi
  • Glutathione Transferase / biosynthesis
  • Insulin-Like Growth Factor I / biosynthesis
  • Insulin-Like Growth Factor I / genetics
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism*
  • Interleukin-1 / pharmacology
  • Isoenzymes / biosynthesis
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / metabolism
  • Microglia / pathology
  • Myelin Sheath / metabolism
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology
  • RNA, Messenger / metabolism
  • Regeneration / drug effects
  • Regeneration / physiology*
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Up-Regulation / drug effects

Substances

  • Antigens, Differentiation
  • Chelating Agents
  • Interleukin-1
  • Isoenzymes
  • RNA, Messenger
  • Cuprizone
  • Insulin-Like Growth Factor I
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Gstp1 protein, mouse