The release of tumor necrosis factor–α is associated with ischemic tolerance in human stroke

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Abstract
Tumor necrosis factor (TNF)–α overexpression has been related to experimental ischemic tolerance when transient ischemia precedes cerebral infarction. We investigated TNF‐α and interleukin (IL)–6 plasma concentrations in 283 patients with an acute stroke within 24 hours after symptom onset. An ipsilateral transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38 patients. The infarct volume measured on computed tomography on days 4 to 7 and the frequency of poor outcome (Barthel Index score < 85) at 3 months were significantly lower in patients with prior TIA. Plasma concentrations of TNF‐α were higher (42.5 ± 9.9 vs 13.1 ± 6.4pg/ml, p < 0.0001) and IL‐6 levels were lower (10.1 ± 6.2 vs 28.3 ± 17.3pg/ml, p < 0.0001) in patients with prior TIA. A new variable termed TNF‐α/IL‐6 index was considered positive when TNF‐α was greater than 30pg/ml and IL‐6 was less than 30pg/ml. Positive TNF‐α/IL‐6 index was found in 92% of patients with prior TIA and in 1% of those without. TNF‐α/IL‐6 index (p = 0.0003) and TIA (p = 0.0001) were associated with good outcome in logistic regression analysis after adjusting for potential confounding factors. Ischemic tolerance in acute stroke is associated with increased plasma levels of TNF‐α in the presence of reduced concentrations of IL‐6. Ann Neurol 2003;54:811–819