Resveratrol inhibits interleukin-6 production in cortical mixed glial cells under hypoxia/hypoglycemia followed by reoxygenation

Reactive oxygen intermediates (ROIs) are important mediators of a variety of pathological processes, including inflammation and ischemia/reperfusion injury. Cytokines and chemokines are detected at mRNA level in human and animal ischemic brains. This suggests that hypoxia/reoxygenation may induce cytokine production through generation of ROIs. In this study, we investigated the cytokine induction and inhibition by antioxidants in rat cortical mixed glial cells exposed to in vitro ischemia-like insults (hypoxia plus glucose deprivation). The results showed that interleukin-6 (IL-6) mRNA and protein, but not tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta), were induced during hypoxia/hypoglycemia followed by reoxygenation in the mixed glial cells. The accumulation of IL-6 mRNA was induced as early as 15 min after hypoxia/hypoglycemia and its level was further increased after subsequent reoxygenation. Among the antioxidants studied, only resveratrol suppressed IL-6 gene expression and protein secretion in mixed glial cultures under hypoxia/hypoglycemia followed by reoxygenation. These findings suggest that resveratrol might be useful in treating ischemic-induced inflammatory processes in stroke. (C) 2001 Elsevier Science B.V. All rights reserved.