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(Stroke. 2000;31:1715.)
© 2000 American Heart Association, Inc.

Original Contributions

Lack of Interleukin-6 Expression Is Not Protective Against Focal Central Nervous System Ischemia

Wayne M. Clark, MD; Lisa G. Rinker, BS; Nikola S. Lessov, MD; Kristin Hazel, BA; Jennifer K. Hill, BS; Mary Stenzel-Poore, PhD Felix Eckenstein, PhD

From the Oregon Stroke Center, Departments of Neurology (W.M.C., L.G.R., N.S.L., K.H.) and Cell Biology (J.K.H., M.S.-P., F.E.), Oregon Health Sciences University, Portland.

Correspondence to Wayne Clark, MD, Oregon Stroke Center, UHS 44, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201. E-mail clarkw{at}ohsu.edu

Background and Purpose—Interleukin-6 (IL-6) appears to be involved in the inflammatory response associated with central nervous system (CNS) ischemia. Although IL-6 levels increase after stroke, it is not known whether IL-6 directly influences CNS ischemic injury. In this study, we used a focal reversible stroke model to investigate whether mice lacking IL-6 were protected against acute ischemic injury.

Methods—We bred IL-6–deficient C57 black mice (I-129 IL-6 KO back-crossed with C57), including homozygous knockouts (IL-6 -/-), heterozygous littermates (IL-6 +/-), and normal littermates (IL-6 +/+). The status of all animals was confirmed by DNA sampling and polymerase chain reaction analysis. Reversible middle cerebral artery occlusion was produced by advancing a silicone-coated 8-0 filament into the internal carotid artery for 2 hours (experiment 1) or 45 minutes (experiment 2). At 24 hours, animals were evaluated on a 28-point clinical scale, blood and cerebrospinal fluid were obtained, and the brains were evaluated for infarct volume and IL-6 mRNA levels.

Results—In experiment 1 (severe ischemia), no differences were seen in lesion size or neurological function between the groups: lesion volume was IL-6 -/- (n=15), 57±13 mm³; IL-6 +/- (n=15), 58±23 mm³; and IL-6 +/+ (n=15), 58±18 mm³ (P=NS). ELISA testing confirmed very low to absent levels of IL-6 in the serum and cerebrospinal fluid of knockout animals. Brain mRNA levels of the other proinflammatory cytokines, including tumor necrosis factor-, IL-1ß, and IL-1 receptor antagonist, were 50% lower in IL-6–deficient ischemic animals than in normal animals. In experiment 2 (mild ischemia), no differences were seen in lesion size or neurological function between the groups: lesion volume was IL-6 -/- (n=10), 16±8 mm³; IL-6 +/- (n=10), 14±4 mm³; and IL-6 +/+ (n=10), 19±12 mm³ (P=NS).

Conclusions—In this study, infarct size and neurological function at 24 hours were not different in animals deficient in IL-6 after transient CNS ischemia. This suggests that IL-6 does not have a direct influence on acute ischemic injury. Further study investigating the role of IL-6 on long-term recovery after stroke is in progress.

Editorial Comment

E. Clarke Haley, Jr, MD, Guest Editor

Department of Neurology University of Virginia Health System Charlottesville, Virginia

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