Role of IL-1alpha and IL-1beta in ischemic brain damage.

Abstract

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-1beta rather than IL-1alpha, 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-1alpha, IL-1beta, or both IL-1alpha and IL-1beta 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-1alpha or IL-1beta alone. IL-1beta mRNA, but not IL-1alpha or the IL-1 type 1 receptor, was strongly induced by MCAO in WT and IL-1alpha KO mice. Administration (intracerebroventricularly) of recombinant IL-1 receptor antagonist significantly reduced infarct volume in WT (-32%) and IL-1alpha KO (-48%) mice, but had no effect on injury in IL-1beta or IL-1alpha/beta KO mice. These data confirm that IL-1 plays a major role in ischemic brain injury. They also show that chronic deletion of IL-1alpha or IL-1beta fails to influence brain damage, probably because of compensatory changes in the IL-1 system in IL-1alpha KO mice and changes in IL-1-independent mediators of neuronal death in IL-1beta KO mice.

• Authors: H Boutin, R A LeFeuvre, R Horai, M Asano, Y Iwakura, N J Rothwell
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 21 Issue 15 Pg. 5528-34 (Aug 01 2001) ISSN: 1529-2401 [Electronic] United States
• PMID: 11466424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Il1rn protein, mouse
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1
• RNA, Messenger
• Receptors, Interleukin-1
• Receptors, Interleukin-1 Type I
• Sialoglycoproteins

Topics

• Animals
• Blood Flow Velocity
• Brain (blood supply, drug effects, metabolism, pathology)
• Cerebrovascular Circulation
• Infarction, Middle Cerebral Artery (complications)
• Injections, Intraventricular
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1 (deficiency, genetics, metabolism)
• Ischemic Attack, Transient (etiology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• RNA, Messenger (metabolism)
• Receptors, Interleukin-1 (antagonists & inhibitors, genetics, metabolism)
• Receptors, Interleukin-1 Type I
• Reverse Transcriptase Polymerase Chain Reaction
• Sialoglycoproteins (administration & dosage)