Time course of IL-6 expression in experimental CNS ischemia

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; pg ml-1; 24 h, 320 +/- 314* pg ml-1; 72 h, 20 +/- 30* pg ml-1 (*p < or = 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 < or = 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.

Inflammatory Response and Glutathione Peroxidase in a Model of Stroke

“…There is strong evidence implicating several inflammatory cytokines and their receptors in exacerbation of focal I/R damage, although protective effects for TNF-␣ and IL-6 also were also reported. Levels of IL-6 had a strong correlation with neurologic function and infarct size in animal experimental ischemia as well as in stroke patients (33,34). It was also demonstrated that the IL-6 system plays an important role in local inflammatory reactions by amplifying leukocyte recruitment and changing endothelial permeability (35).…”

Hypoxic Preconditioning Induces Neuroprotective Stanniocalcin-1 in Brain via IL-6 Signaling

“…The concentration of IL-6 giving maximum stimulation was 2.5 ng/mL, ie, a concentration comparable to serum levels of IL-6 recorded in an in vivo experimental mouse central nervous system ischemia model. 21 Notably, exposure of Paju cells to hypoxia overnight did not, however, directly induce increased STC-1 expression (data not shown).…”

Inflammatory mechanisms involved in brain injury following cardiac arrest and cardiopulmonary resuscitation

“…An elevated level of IL-1β can potentiate inflammation by activating microglia and induce the infiltration of peripheral leukocytes by increasing the expression of adhesion molecules on endothelial cells; these events are associated with worsening of the infarct severity and progressive neurodegeneration (81)(82)(83). In addition to its role as a pro-inflammatory mediator, IL-1β can also elevate the expression of other pro-inflammatory cytokines, such as IL-6 and TNF-α, which can be upregulated following cerebral ischemia (84).…”