Expression of interleukin-6 is suppressed by inhibition of voltage-sensitive Na+/Ca2+ channels after cerebral ischemia

Expression of interleukin-6 (IL-6), a neurotrophic cytokine, is up-regulate d after cerebral ischemia, but the underlying mechanism of the up-regulatio n remains unclear. NS-7 is a novel blocker of voltage-sensitive Ca2+ and Na + channels and is known to reduce cerebral damage by ischemia. The present study was undertaken to examine the association between increases in intrac ellular Ca2+ concentration induced by membrane depolarization and IL-6 indu ction. IL-6 expression in rat brain was investigated by immunohistochemistr y and Western blot analysis following 3.5-48 h of reperfusion after 1.5 h o f occlusion of the middle cerebral artery. NS-7 (1 mg/kg; NS-7 group) or sa line (saline group) was injected i.v. 5 min after the start of reperfusion. The saline group showed clear IL-6 expression in various cortical regions, which peaked at 24 h of reperfusion. By contrast, IL-6 expression was sign ificantly suppressed in the NS-7 group throughout the reperfusion period. M icroglia activation was also reduced in the NS-7 group. These findings sugg est that IL-6 expression may be upregulated by the increased intracellular Ca2+ concentration triggered by membrane depolarization after cerebral isch emia. NeuroReport 11:2565-2569 (C) 2000 Lippincott Williams & Wilkins.