Time course of IL-6 expression in experimental CNS ischemia

Abstract

lnterleukin-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 obtainedand 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*pgml^–1; 12h, 980±221 * pg ml^–1; 24 h, 320± 314*pgml^–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*pgml^–1; 6 h, 157±61*pg ml^–1; 12 h, 136± 88*pgml^–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. Neurol Res 1999; 21: 287-292]