Planas A M, Gorina R, Chamorro A
IIBB (Institute for Biomedical Research)--CSIC (Spanish Research Council), IDIBAPS (Institute of Biomedical Investigation 'August Pi i Sunyer'), Rosselló 161, planta 6, E-08036 Barcelona, Spain.
Biochem Soc Trans. 2006 Dec;34(Pt 6):1267-70. doi: 10.1042/BST0341267.
Stroke causes neuronal necrosis and generates inflammation. Pro-inflammatory molecules intervene in this process by triggering glial cell activation and leucocyte infiltration to the injured tissue. Cytokines are major mediators of the inflammatory response. Pro-inflammatory and anti-inflammatory cytokines are released in the ischaemic brain. Anti-inflammatory cytokines, such as interleukin-10, promote cell survival, whereas pro-inflammatory cytokines, such as TNFalpha (tumour necrosis factor alpha), can induce cell death. However, deleterious effects of certain cytokines can turn to beneficial actions, depending on particular features such as the concentration, time point and the very intricate network of intracellular signals that become activated and interact. A key player in the intracellular response to cytokines is the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway that induces alterations in the pattern of gene transcription. These changes are associated either with cell death or survival depending, among other things, on the specific proteins involved. STAT1 activation is related to cell death, whereas STAT3 activation is often associated with survival. Yet, it is clear that STAT activation must be tightly controlled, and for this reason the function of JAK/STAT modulators, such as SOCS (suppressors of cytokine signalling) and PIAS (protein inhibitor of activated STAT), and phosphatases is most relevant. Besides local effects in the ischaemic brain, cytokines are released to the circulation and affect the immune system. Unbalanced pro-inflammatory and anti-inflammatory plasma cytokine concentrations favouring an 'anti-inflammatory' state can decrease the immune response. Robust evidence now supports that stroke can induce an immunodepression syndrome, increasing the risk of infection. The contribution of individual cytokines and their intracellular signalling pathways to this response needs to be further investigated.
中风会导致神经元坏死并引发炎症。促炎分子通过触发胶质细胞活化和白细胞浸润到受损组织中来干预这一过程。细胞因子是炎症反应的主要介质。促炎细胞因子和抗炎细胞因子在缺血性脑中释放。抗炎细胞因子，如白细胞介素-10，可促进细胞存活，而促炎细胞因子，如肿瘤坏死因子α（TNFα），可诱导细胞死亡。然而，某些细胞因子的有害作用可能会转变为有益作用，这取决于特定的特征，如浓度、时间点以及被激活并相互作用的非常复杂的细胞内信号网络。细胞内对细胞因子反应的一个关键参与者是JAK（Janus激酶）/STAT（信号转导和转录激活因子）途径，该途径可诱导基因转录模式的改变。这些变化与细胞死亡或存活相关，这尤其取决于所涉及的特定蛋白质。STAT1的激活与细胞死亡有关，而STAT3的激活通常与存活有关。然而，很明显，STAT的激活必须受到严格控制，因此JAK/STAT调节剂，如细胞因子信号抑制因子（SOCS）和活化STAT蛋白抑制剂（PIAS）以及磷酸酶的功能最为重要。除了在缺血性脑中的局部作用外，细胞因子还会释放到循环系统中并影响免疫系统。促炎和抗炎血浆细胞因子浓度失衡，倾向于“抗炎”状态，会降低免疫反应。现在有确凿的证据支持中风可诱发免疫抑制综合征，增加感染风险。需要进一步研究个体细胞因子及其细胞内信号通路对这种反应的贡献。
