Interleukin-1α expression precedes IL-1β after ischemic brain injury and is localised to areas of focal neuronal loss and penumbral tissues.
BACKGROUND
Cerebral ischemia is a devastating condition in which the outcome is heavily influenced by inflammatory processes, which can augment primary injury caused by reduced blood supply. The cytokines interleukin-1α (IL-1α) and IL-1β are key contributors to ischemic brain injury. However, there is very little evidence that IL-1 expression occurs at the protein level early enough (within hours) to influence brain damage after stroke. In order to determine this we investigated the temporal and spatial profiles of IL-1α and IL-1β expression after cerebral ischemia.


RESULTS
We report here that in mice, as early as 4 h after reperfusion following ischemia induced by occlusion of the middle cerebral artery, IL-1α, but not IL-1β, is expressed by microglia-like cells in the ischemic hemisphere, which parallels an upregulation of IL-1α mRNA. 24 h after ischemia IL-1α expression is closely associated with areas of focal blood brain barrier breakdown and neuronal death, mostly near the penumbra surrounding the infarct. The sub-cellular distribution of IL-1α in injured areas is not uniform suggesting that it is regulated.


CONCLUSIONS
The early expression of IL-1α in areas of focal neuronal injury suggests that it is the major form of IL-1 contributing to inflammation early after cerebral ischemia. This adds to the growing body of evidence that IL-1α is a key mediator of the sterile inflammatory response.
University of Manchester, UK.
Nadia M
NM
Luheshi
Krisztina J
KJ
Kovács
Gloria
G
Lopez-Castejon
David
D
Brough
Adam
A
Denes
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000276:immunology* / Q000473:pathology*; D002545:Brain Ischemia / Q000276:immunology* / Q000473:pathology*; D000073883:CX3C Chemokine Receptor 1; D020244:Infarction, Middle Cerebral Artery; D053582:Interleukin-1alpha / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000276:immunology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology
D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D019707:Receptors, Chemokine