TY - JOUR
T1 - Lack of interleukin-6 expression is not protective against focal central nervous system ischemia
AU - Clark, Wayne M.
AU - Rinker, Lisa G.
AU - Lessov, Nikola S.
AU - Hazel, Kristin
AU - Hill, Jennifer K.
AU - Stenzel-Poore, Mary
AU - Eckenstein, Felix
PY - 2000/7
Y1 - 2000/7
N2 - 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-α, IL-1β, 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.
AB - 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-α, IL-1β, 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.
KW - Inflammation
KW - Interleukins
KW - Mice, knockout
KW - Stroke
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U2 - 10.1161/01.STR.31.7.1715
DO - 10.1161/01.STR.31.7.1715
M3 - Article
C2 - 10884478
AN - SCOPUS:0033933545
SN - 0039-2499
VL - 31
SP - 1715
EP - 1720
JO - Stroke
JF - Stroke
IS - 7
ER -