Time course of IL-6 expression in experimental CNS ischemia

Wayne M. Clark, Lisa G. Rinker, Nikola S. Lessov, Kristin Hazel, Felix Eckenstein

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Interleukin-6 (IL-6) appears to be an important modulator of the inflammatory response associated with CNS ischemia. Clinically, IL-6 values obtained in the first week post-stroke have been shown to correlate with infarct size and outcome. In this study we used a focal reversible stroke model to investigate the time course and relationship to outcome of IL-6 production in plasma, brain and CSF. Reversible middle cerebral artery occlusion or sham surgery was produced in 50 adult Swiss Webster mice by advancing an 8-0 filament into the internal carotid artery for 2 h (sham 1 min). At 3, 6, 12, 24, and 72 h (8 each ischemia; 2 each sham) groups of animals were evaluated on a 28 point clinical scale, blood and CSF obtained, and the brains were evaluated for infarct volume and IL-6 mRNA levels. Serum levels of IL-6 (ELISA mean ± SD; undetectable in controls) overall sham group, 102 ± 87; 3 h, 908 ± 494 * pg ml-1; 6 h, 1079 ± 468 * pg ml- 1; 12 h, 980 ± 221 * pg ml-1; 24 h, 320 ± 314 * pg ml-1; 72 h, 20 ± 30 * pg ml-1 (* p < 0.05 to sham). CSF levels (ELISA) overall sham group, 10 ± 18; 3 h, 379 ± 210 * pg ml-1; 6 h, 157 ± 61 * pg ml-1; 12 h, 136 ± 88 * pg ml-1; 24 h, 127 ± 99 pg ml-1; 72 h, 72 ± 9 * pg ml- 1 (* p ≤ 0.05 to sham). Brain IL-6 mRNA levels overall sham group, 20; 3 h, 480; 6 h, 599; 12 h, 7960; 24 h, 20267; 72 h, 0. There was an overall R2 of 0.20 between plasma and CSF IL-6. There was an overall R2 of 0.13 and 0.20 between infarct size and serum and CSF IL-6 level respectively, and an overall R2 of 0.10 and 0.17 between neurologic function and serum and CSF IL-6 level respectively. These findings confirm that IL-6 values increase following CNS ischemia with peak serum and CSF levels occurring before brain values. CSF IL-6 levels had a stronger correlation with neurologic function and infarct size than serum.

Original languageEnglish (US)
Pages (from-to)287-292
Number of pages6
JournalNeurological Research
Volume21
Issue number3
DOIs
StatePublished - 1999

Keywords

  • CNS ischemia
  • Infarct size
  • Inflammatory response
  • Interleukin-6
  • Neurologic function

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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