Stroke, Vol 24, 1746-1750, Copyright © 1993 by American Heart Association
T Liu, PC McDonnell, PR Young, RF White, AL Siren, JM Hallenbeck, FC Barone and GZ Feurestein
BACKGROUND AND PURPOSE: Interleukin-1 beta is a proinflammatory cytokine
produced by blood-borne and resident brain inflammatory cells. The present
study was conducted to determine if interleukin-1 beta mRNA was produced in
the brain of rats subjected to permanent focal ischemia. METHODS: Rat
interleukin-1 beta cDNA, synthesized from stimulated rat peritoneal
macrophage RNA by reverse transcription and polymerase chain reaction and
cloned in plasmid Bluescript KS+, was used to evaluate the expression of
interleukin-1 beta mRNA in cerebral cortex from spontaneously hypertensive
rats and normotensive rats subjected to permanent middle cerebral artery
occlusion. Interleukin-1 beta mRNA was quantified by Northern blot analysis
and compared with rat macrophage RNA standard. To correct for gel loading,
blots were also analyzed with cyclophilin cDNA, which encodes an abundant,
conserved protein that was unchanged by the experimental conditions.
RESULTS: Interleukin-1 beta mRNA produced in the ischemic zone was
significantly increased from 6 hours to 120 hours, with a maximum of 211
+/- 24% of interleukin-1 beta reference standard, ie, 0.2 ng stimulated rat
macrophage RNA, mRNA compared with the level in nonischemic cortices (4 +/-
2%) at 12 hours after ischemia (P < .01; n = 6). Interleukin-1 beta mRNA
at 12 hours after ischemia was markedly elevated in hypertensive rats over
levels found in two normotensive rat strains. Neurological deficits were
also apparent only in the hypertensive rats. CONCLUSIONS: Brain
interleukin-1 beta mRNA is elevated acutely after permanent focal ischemia
and especially in hypertensive rats. These data suggest that this potent
proinflammatory and procoagulant cytokine might have a role in brain damage
following ischemia.
ARTICLES
Interleukin-1 beta mRNA expression in ischemic rat cortex
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
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