Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice: possible involvement of Stat3 activation in the protection of neurons
Article first published online: 10 JUN 2005
Journal of Neurochemistry
Volume 94, Issue 2, pages 459–468, July 2005
How to Cite
Yamashita, T., Sawamoto, K., Suzuki, S., Suzuki, N., Adachi, K., Kawase, T., Mihara, M., Ohsugi, Y., Abe, K. and Okano, H. (2005), Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice: possible involvement of Stat3 activation in the protection of neurons. Journal of Neurochemistry, 94: 459–468. doi: 10.1111/j.1471-4159.2005.03227.x
- Issue published online: 10 JUN 2005
- Article first published online: 10 JUN 2005
- Received October 21, 2004; revised manuscript received February 15, 2005; accepted April 5, 2005.
- focal cerebral ischemia;
- interleukin-6 receptor antibody;
- signal transducer and activation of transcription-3
Interleukin (IL)-6 expression transiently increases in the acute phase of cerebral ischemia. To investigate the physiological significance of endogenous IL-6 expression and to identify the main signal pathway for the action of IL-6, we administered anti-mouse IL-6 receptor monoclonal antibody (IL-6RA), which blocks IL-6 signaling, to mice immediately after a 45-min period of middle cerebral artery occlusion (MCAO). At 6 h after MCAO, IL-6RA administration had resulted in a significant reduction in the amount of phosphorylated signal transducer and activator of transcription-3 (Stat3) protein in the peri-infarct area of the cortex. At 24 h after MCAO, blockade of IL-6 signaling had led to an increase in number of apoptotic cells in the peri-infarct area and enlargement of the size of the infarct, and it had adversely affected neurological function. These results suggest that endogenous IL-6 plays a critical role in preventing damaged neurons from undergoing apoptosis in the acute phase of cerebral ischemia and that its role may be mediated by Stat3 activation.