Interleukin-1beta promotes repair of the CNS.
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.
Mason
J L
JL
Curriculum in Neurobiology and the University of North Carolina Neuroscience Center, Chapel Hill, North Carolina 27599, USA.
Suzuki
K
K
Chaplin
D D
DD
Matsushima
G K
GK
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002614:Chelating Agents; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000943:Antigens, Differentiation; D002614:Chelating Agents; D007375:Interleukin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D003471:Cuprizone; D007334:Insulin-Like Growth Factor I; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496557:Gstp1 protein, mouse