Role of IL-1α and IL-1β in ischemic brain damage
H Boutin, RA LeFeuvre, R Horai, M Asano… - Journal of …, 2001 - Soc Neuroscience
H Boutin, RA LeFeuvre, R Horai, M Asano, Y Iwakura, NJ Rothwell
Journal of Neuroscience, 2001•Soc NeuroscienceThe 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-1β rather than IL-1α, 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-1α, IL-
1β, or both IL-1α and IL-1β knock-out (KO) mice. Mice lacking both forms of IL-1 exhibited …
ischemic brain damage. Evidence to date suggests that the major form of IL-1 contributing to
ischemic injury is IL-1β rather than IL-1α, 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-1α, IL-
1β, or both IL-1α and IL-1β knock-out (KO) mice. Mice lacking both forms of IL-1 exhibited …
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-1β rather than IL-1α, 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-1α, IL-1β, or both IL-1α and IL-1β 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-1α or IL-1β alone. IL-1β mRNA, but not IL-1α or the IL-1 type 1 receptor, was strongly induced by MCAO in WT and IL-1α KO mice.
Administration (intracerebroventricularly) of recombinant IL-1 receptor antagonist significantly reduced infarct volume in WT (-32%) and IL-1α KO (-48%) mice, but had no effect on injury in IL-1β or IL-1α/β KO mice.
These data confirm that IL-1 plays a major role in ischemic brain injury. They also show that chronic deletion of IL-1α or IL-1β fails to influence brain damage, probably because of compensatory changes in the IL-1 system in IL-1α KO mice and changes in IL-1-independent mediators of neuronal death in IL-1β KO mice.
Soc Neuroscience