Interleukin-1 beta mRNA expression in ischemic rat cortex.
OBJECTIVE
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.
Liu
T
T
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
McDonnell
P C
PC
Young
P R
PR
White
R F
RF
Siren
A L
AL
Hallenbeck
J M
JM
Barone
F C
FC
Feurestein
G Z
GZ
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology; D001483:Base Sequence; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology; D002539:Cerebral Arterial Diseases / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism*; D017931:DNA Primers; D015870:Gene Expression; D007375:Interleukin-1 / Q000096:biosynthesis*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D008969:Molecular Sequence Data; D009043:Motor Activity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012016:Reference Values; D013997:Time Factors; D014158:Transcription, Genetic
D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger