Proinflammatory cytokines and early neurological worsening in ischemic stroke

Background and Purpose-The mechanisms for clinical deterioration in patient s with ischemic stroke are not completely understood. Several proinflammato ry cytokines are released early after the onset of brain ischemia, but it i s unknown whether inflammation predisposes to neurological deterioration. W e assessed the implication of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in early neurological worsening in ischemic stroke. Methods-Two hundred thirty-one patients consecutively admitted with first-e ver ischemic cerebral infarction within the first 24 hours from onset were included. Neurological worsening was defined when the Canadian Stroke Scale (CSS) score fell at least 1 point during the first 48 hours after admissio n. IL-6 and TNF-alpha were determined in plasma and cerebrospinal fluid (CS F; n=81) obtained on admission. Results-Eighty-three patients (35.9%) deteriorated within the first 48 hour s. IL-6 in plasma (>21.5 pg/mL; OR 37.7, CI 11.9 to 118.8) or in CSF (>6.3 pg/mL; OR 13.1, CI 2.2 to 77.3) were independent factors for early clinical worsening with multiple logistic regression, The association was statistic ally significant in all ischemic stroke subtypes as well as in subjects wit h cortical or subcortical infarctions. IL-6 in plasma was highly correlated with body temperature, glucose, fibrinogen, and infarct volume, CSF and pl asma concentrations of TNF-alpha were also higher in patients who deteriora ted, bur the differences observed did not remain significant on multivariat e analysis. Conclusions-In addition to participating in the acute-phase response that f ollows focal cerebral ischemia, IL-6 levels on admission an associated with early clinical deterioration. The association between IL-6 and early neuro logical worsening prevails without regard to the initial size, topography, or mechanism of the ischemic infarction.