Gourine Alexander V, Poputnikov Dmitry M, Zhernosek Nikolai, Melenchuk Ekaterina V, Gerstberger Rüdiger, Spyer K Michael, Gourine Valery N
1Department of Physiology, Royal Free and University College London Medical School, University College London, Hampstead Campus, UK.
Br J Pharmacol. 2005 Sep;146(1):139-45. doi: 10.1038/sj.bjp.0706287.
Adenosine 5'-triphosphate (ATP) has been shown to induce release of cytokines implicated in fever, including interleukin(IL)-1beta, IL-6, and tumour necrosis factor-alpha (TNF-alpha). The role of ATP-mediated purinergic signalling in fever and cytokine release during systemic inflammation was investigated by studying the effects of P2 receptor antagonists suramin, pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), and Brilliant Blue G (BBG) on changes in body temperature and the increases in plasma levels of IL-1beta, IL-6, and TNFalpha induced by bacterial lipopolysaccharide (LPS) in rats. LPS (Escherichia coli; 50 microg kg(-1))-induced febrile response was attenuated by suramin (25 mg kg(-1) and 100 mg kg(-1)), PPADS (25 mg kg(-1)), and a more selective P2X(7) receptor antagonist BBG (100 mg kg(-1)) injected intraperitoneally before the induction of fever. The increase in plasma concentrations of IL-1beta and IL-6, measured 1 h after LPS treatment, was reduced by PPADS (25 mg kg(-1)) and BBG (100 mg kg(-1)). LPS-induced increase in plasma TNF-alpha concentration was also markedly attenuated by BBG (100 mg kg(-1)), but not by PPADS (25 mg kg(-1)). These data indicate that purinergic signalling plays an important role in the mechanisms responsible for the LPS-induced febrile response and increases in the levels of circulating cytokines. We suggest that ATP acting via P2X(7) receptors induces release of pyrogenic cytokines to mediate fever during systemic inflammation.
已证明5'-三磷酸腺苷（ATP）可诱导释放与发热相关的细胞因子，包括白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α（TNF-α）。通过研究P2受体拮抗剂苏拉明、5'-磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸（PPADS）和亮蓝G（BBG）对大鼠体温变化以及细菌脂多糖（LPS）诱导的血浆IL-1β、IL-6和TNF-α水平升高的影响，探讨了ATP介导的嘌呤能信号在全身炎症期间发热和细胞因子释放中的作用。在发热诱导前腹腔注射苏拉明（25 mg kg(-1)和100 mg kg(-1)）、PPADS（25 mg kg(-1)）和更具选择性的P2X(7)受体拮抗剂BBG（100 mg kg(-1)），可减弱LPS（大肠杆菌；50 μg kg(-1)）诱导的发热反应。LPS处理1小时后测量的血浆IL-1β和IL-6浓度升高，被PPADS（25 mg kg(-1)）和BBG（100 mg kg(-1)）降低。BBG（100 mg kg(-1)）也显著减弱了LPS诱导的血浆TNF-α浓度升高，但PPADS（25 mg kg(-1)）没有。这些数据表明，嘌呤能信号在LPS诱导的发热反应和循环细胞因子水平升高的机制中起重要作用。我们认为，在全身炎症期间，通过P2X(7)受体起作用的ATP诱导热原性细胞因子释放以介导发热。
