Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
Brain Behav Immun. 2016 May;54:1-14. doi: 10.1016/j.bbi.2015.09.003. Epub 2015 Sep 5.
Immune-to-brain communication pathways involve humoral mediators, including cytokines, central modulation by neuronal afferents and immune cell trafficking to the brain. During systemic inflammation these pathways contribute to mediating brain-controlled sickness symptoms including fever. Experimentally, activation of these signaling pathways can be mimicked and studied when injecting animals with pathogen associated molecular patterns (PAMPS). One central component of the brain inflammatory response, which leads, for example, to fever induction, is transcriptional activation of brain cells via cytokines and PAMPS. We and others have studied the spatiotemporal activation and the physiological significance of transcription factors for the induction of inflammation within the brain and the manifestation of fever. Evidence has revealed a role of nuclear factor (NF)κB in the initiation, signal transducer and activator of transcription (STAT)3 in the maintenance and NF-interleukin (IL)6 in the maintenance or even termination of brain-inflammation and fever. Moreover, psychological stressors, such as exposure to a novel environment, leads to increased body core temperature and genomic NF-IL6-activation, suggesting a potential use of NF-IL6-immunohistochemistry as a multimodal brain cell activation marker and a role for NF-IL6 for differential brain activity. In addition, the nutritional status, as reflected by circulating levels of the cytokine-like hormone leptin, influence immune-to-brain communication and age-dependent changes in LPS-induced fever. Overall, transcription factors remain therapeutically important targets for the treatment of brain-inflammation and fever induction during infectious/non-infectious inflammatory and psychological stress. However, the exact physiological role and significance of these transcription factors requires to be further investigated.
免疫与脑通讯途径涉及体液介质，包括细胞因子、神经元传入的中枢调节以及免疫细胞向脑的迁移。在全身炎症反应期间，这些途径有助于介导脑控制的疾病症状，包括发热。在实验中，通过向动物注射病原体相关分子模式 (PAMPS) 可以模拟和研究这些信号通路的激活。脑炎症反应的一个核心组成部分，例如导致发热诱导，是通过细胞因子和 PAMPS 对脑细胞的转录激活。我们和其他人研究了转录因子在脑内炎症诱导和发热表现中的时空激活及其生理意义。有证据表明，核因子 (NF)-κB 在启动、信号转导和转录激活因子 (STAT)3 在维持以及 NF-白细胞介素 (IL)-6 在维持甚至终止脑炎症和发热中起作用。此外，心理应激源，如暴露于新环境，会导致体温核心升高和基因组 NF-IL6 激活，这表明 NF-IL6 免疫组织化学作为一种多模态脑细胞激活标志物的潜在用途，以及 NF-IL6 对脑活动的差异的作用。此外，营养状况，如细胞因子样激素瘦素的循环水平反映，影响免疫与脑通讯和 LPS 诱导发热的年龄相关变化。总的来说，转录因子仍然是治疗感染/非感染性炎症和心理应激期间脑炎症和发热诱导的重要治疗靶点。然而，这些转录因子的确切生理作用和意义需要进一步研究。
