Temporal profile and cellular localization of interleukin-6 protein after focal cerebral ischemia in rats

Although interleukin-6 (IL-6) has various neuroprotective effects against c erebral ischemia, the topographic distribution and cellular source of IL-6 after cerebral ischemia remain unclear. In the current study, the localizat ion of IL-6 protein was immunohistochemically examined in rats after 3.5, 1 2, 24, and 48 hours of reperfusion after 1.5 hours of middle cerebral arter y occlusion. Middle cerebral artery occlusion was induced by the intralumin al suture method. The specificity of the anti-IL-6 antibody used in the cur rent study was confirmed by Western blot analysis and an immunoabsorption t est. To identify the cellular source, lectin histochemical study and immuno histochemical study with microtubule-associated protein-2, ED1, and glial f ibrillary acidic protein also were carried out. The sham group did not show any clear IL-6 immunoreactivity. After 3.5 hours of reperfusion, IL-6 inmu noreactivity was first detected on the reperfused side, and it was upregula ted, especially in the periinfarct region, after 3.5 hours of reperfusion. Also, IL-6 was expressed after 3.5 hours of reperfusion in the contralatera l cerebral cortex and bilateral hippocampi. Double staining showed that the cells containing IL-G were neurons and round-type microglia, not astrocyte s. The current findings suggest that IL-6 expression in ischemically threat ened neurons and reactive microglia is closely associated with brain tissue neuroprotective mechanisms against cerebral ischemia.