IL-6 deficiency causes enhanced pathology in Twitcher (globoid cell leukodystrophy) mice.

Pedchenko TV, LeVine SM
Exp Neurol. 1999 158 (2): 459-68

PMID: 10415153 · DOI:10.1006/exnr.1999.7125

The expression of IL-6 is greatly enhanced in the twitcher mouse (S. M. LeVine and D. C. Brown, 1997, J. Neuroimmunol. 73, 47-56), which is an authentic animal model of globoid cell leukodystrophy (Krabbe's disease). In order to investigate the role of IL-6 in this disease, twitcher/IL-6-deficient mice were generated and the pathology was compared between them and regular twitcher mice. Twitcher/IL-6-deficient mice had a more severe disease than regular twitcher mice: they had an earlier onset day of twitching, a greater number of PAS-positive cells, a greater susceptibility to LPS, an exaggerated gliotic response around some vessels, an elevated level of TNF-alpha, and a compromised blood-brain barrier, which was evaluated by three independent measures. This latter finding indicates that IL-6 plays a role in maintaining the integrity of the BBB, and it raises the possibility that IL-6 functions in a similar manner in other diseases of the CNS. LPS was found to greatly shorten the life of twitcher and twitcher/IL-6-deficient mice compared to genotyped-matched saline-injected mice. This result indicates that a proinflammatory condition can exacerbate an underlying CNS pathology, which could help explain why some leukodystrophy patients display their initial symptoms following a fever or blow to the head.

Copyright 1999 Academic Press.

MeSH Terms (19)

Animals Blood-Brain Barrier Brain Crosses, Genetic Disease Progression Escherichia coli Glial Fibrillary Acidic Protein Interleukin-6 Lectins Leukodystrophy, Globoid Cell Lipopolysaccharides Mice Mice, Inbred C57BL Mice, Knockout Mice, Neurologic Mutants Motor Activity Myelin Basic Protein Rhombencephalon Tumor Necrosis Factor-alpha

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