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(Stroke. 1997;28:155-162.)
© 1997 American Heart Association, Inc.

Articles

Interleukin-1 Receptor and Receptor Antagonist Gene Expression After Focal Stroke in Rats

Xinkang Wang, PhD; Frank C. Barone, PhD; Nambi V. Aiyar, PhD Giora Z. Feuerstein, MD

the Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.

Correspondence to Xinkang Wang, PhD, Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd, PO Box 1539, UW2511, King of Prussia, PA 19406. E-mail xinkang_wang-1@sbphrd.com.

Background and Purpose The expression of interleukin-1ß (IL-1ß) is upregulated after focal brain ischemia, and previous work has demonstrated its involvement in ischemic injury. The IL-1 receptor antagonist (IL-1ra), a natural competitive antagonist of IL-1 receptors (IL-1Rs), has been demonstrated to play a role in attenuating brain ischemic injury. To hypothesize the involvement of the IL-1 system in ischemic injury, we examined other IL-1 components, including IL-1ra, IL-1RI, and IL-1RII for their mRNA expression after focal stroke.

Methods Quantitative reverse transcription and polymerase chain reaction (RT-PCR) technique was used to examine the mRNA expression profile of IL-1ra and two IL-1R isoforms in a temporal fashion (n=4 for each time point) after permanent occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive rats. IL-1ra and IL-1R mRNA expression was confirmed by Northern blot analysis using poly(A) RNA isolated after 2 and 12 hours of MCAO.

Results Very low levels of IL-1ra mRNA were detected in sham-operated or nonischemic cortex. IL-1ra mRNA in ischemic cortex was greatly increased at 12 hours (16.5-fold increase over sham samples, P<.001) and remained elevated for up to 5 days (17.2-fold increase, P<.01) after MCAO. IL-1RI mRNA was relatively highly expressed in normal cortex and was further elevated late after ischemic injury (3.3-fold increase at day 5, P<.001). In contrast, the low basal expression of IL-1RII mRNA was remarkably elevated at 6 hours (5.3-fold increase, P<.05), reaching peak levels 12 hours (10.3-fold increase, P<.001) after MCAO.

Conclusions Differential expression of IL-1ß, IL-1ra, IL-1RI, and IL-1RII mRNAs after focal stroke may suggest a distinct role(s) for each component of the IL-1 system in ischemic injury. The data also stress the importance of evaluating all the components of a given cytokine system (eg, agonist, receptors, and natural antagonist) after focal stroke.

Editorial Comment

Gregory J. del Zoppo, MD, Guest Editor

Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, Calif

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