Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline

作者：Terrando Niccolo; Monaco Claudia; Ma Daqing; Foxwell Brian M J; Feldmann Marc^*; Maze Mervyn

来源：Proceedings of the National Academy of Sciences, 2010, 107(47): 20518-20522.

DOI：10.1073/pnas.1014557107

• innate immunity
• surgical complications
• delirium
• dementia

Cognitive decline following surgery in older individuals is a major clinical problem of uncertain mechanism; a similar cognitive decline also follows severe infection, chemotherapy, or trauma and is currently without effective therapy. A variety of mechanisms have been proposed, and exploring the role of inflammation, we recently reported the role of IL-1 beta in the hippocampus after surgery in mice with postoperative cognitive dysfunction. Here, we show that TNF-alpha is upstream of IL-1 and provokes its production in the brain. Peripheral blockade of TNF-alpha is able to limit the release of IL-1 and prevent neuroinflammation and cognitive decline in a mouse model of surgery-induced cognitive decline. TNF-alpha appears to synergize with MyD88, the IL-1/TLR superfamily common signaling pathway, to sustain postoperative cognitive decline. Taken together, our results suggest a unique therapeutic potential for preemptive treatment with anti-TNF antibody to prevent surgery-induced cognitive decline.

• 出版日期2010-11-23