INTRATHECAL RELEASE OF PROINFLAMMATORY AND ANTIINFLAMMATORY CYTOKINESDURING STROKE

A growing body of evidence points out the potential role of inflammato ry mechanisms in the pathophysiology of ischaemic brain damage. We hav e recently demonstrated that stroke patients display an intrathecal pr oduction of proinflammatory cytokines, such as IL-1 beta and IL-6 alre ady within the first 24 h after the beginning of symptoms (Tarkowski e t al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thi rty stroke patients were studied prospectively on days 0-3, 7-9, 21-26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition , 15 healthy control CSF samples were used. Significantly increased CS F levels of IL-8, granulocyte-macrophage colony-stimulating factor (GM -CSF) and IL-IO were observed early during the stroke with a peak on d ay 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 f or the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis fact or-alpha (TNF-alpha) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinfla mmatory and immunoregulatory cytokines in patients with stroke, suppor ting the notion of localized immune response to the acute brain lesion . A better understanding of the inflammatory response in stroke may le ad to new treatment strategies.