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The Journal of Neuroscience, August 1, 2001, 21(15):5528-5534
Role of IL-1 and IL-1 in Ischemic Brain Damage
H.
Boutin1,
R. A.
LeFeuvre1,
R.
Horai2,
M.
Asano3,
Y.
Iwakura2, and
N. J.
Rothwell1
1 School of Biological Sciences, University of
Manchester, Manchester M13 9PT, United Kingdom, 2 Center
for Experimental Medicine, Institute of Medical Science, University of
Tokyo, Minato-ku, Tokyo, 108-8639, Japan, and 3 Institute
for Experimental Animals, Faculty of Medicine, Kanazawa University,
Kanazawa 920-8640, Japan
The cytokine interleukin-1 (IL-1) has been strongly implicated in
the pathogenesis of ischemic brain damage. Evidence to date suggests
that the major form of IL-1 contributing to ischemic injury is IL-1
rather than IL-1 , but this has not been tested directly.
The objective of the present study was to compare the effects of
transient cerebral ischemia [30 min middle cerebral artery occlusion
(MCAO)] on neuronal injury in wild-type (WT) mice and in IL-1,
IL-1, or both IL-1 and IL-1 knock-out (KO) mice.
Mice lacking both forms of IL-1 exhibited dramatically reduced ischemic
infarct volumes compared with wild type (total volume, 70%; cortex,
87% reduction). Ischemic damage compared with WT mice was not
significantly altered in mice lacking either IL-1 or IL-1 alone.
IL-1 mRNA, but not IL-1 or the IL-1 type 1 receptor, was strongly
induced by MCAO in WT and IL-1 KO mice.
Administration (intracerebroventricularly) of recombinant IL-1 receptor
antagonist significantly reduced infarct volume in WT (-32%)
and IL-1 KO (-48%) mice, but had no effect on injury in IL-1 or
IL-1/ KO mice.
These data confirm that IL-1 plays a major role in ischemic brain
injury. They also show that chronic deletion of IL-1 or IL-1
fails to influence brain damage, probably because of compensatory changes in the IL-1 system in IL-1 KO mice and changes in
IL-1-independent mediators of neuronal death in IL-1 KO mice.
Key words:
interleukin-1; cytokines; stroke; brain; knock-out; mouse
Copyright © 2001 Society for Neuroscience 0270-6474/01/21155528-07$05.00/0
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