Localized inflammation in peripheral tissue signals the CNS for sickness response in the absence of interleukin-1 and cyclooxygenase-2 in the blood and brain.-猫眼课题宝

DOI：

10.1016/j.neuroscience.2008.09.038

发表时间：

2008-12-10

期刊：

Neuroscience

影响因子：

3.3

通讯作者：

中科院分区：

医学3区

文献类型：

作者：

Zhang H;Ching S;Chen Q;Li Q;An Y;Quan N

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642963/?report=classic

The central nervous system (CNS) can be activated by both local and systemic inflammation, resulting in the manifestation of sickness symptoms. The pathways by which the CNS is activated under these two conditions, however, may differ. In this study, we injected casein into the peritoneal cavity (ip) or into a subcutaneous air pouch to induce restricted local inflammation. Both routes of casein injection caused fever and reduced locomotor activity. These responses were not accompanied by the statistically significant induction of the inflammatory cytokine interleukin-1 (IL-1) in the blood and brain. Further, these responses were produced without the induction of brain cyclooxygenase-2 (COX-2), which has been implicated as an obligatory step in systemic inflammation-induced activation of the CNS. Induction of IL-1, IL-6, and COX-2, however, was found consistently at the sites of casein injection. The local inflammation-induced febrile and locomotor activity responses were blunted in animals deficient in functional Toll-Like Receptor 4 (TLR4), IL-1R1, IL-6, or COX-2. Therefore, the observed febrile and locomotor activity effects appear to require local, but not central, IL-1, IL-6, and COX-2. These findings suggest that local inflammation can activate the CNS via pathways distinguishable from those mediating systemic inflammation-induced CNS activation.