P2 receptor blockade attenuates fever and cytokine responses induced by lipopolysaccharide in rats
P2 receptor blockade attenuates fever and cytokine responses induced by lipopolysaccharide in rats
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DOI：
10.1038/sj.bjp.0706287
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发表时间：
2005-09-01
影响因子：
7.3
通讯作者：
Gourine, VN
中科院分区：
文献类型：
--
作者：
Gourine, AV;Poputnikov, DM;Gourine, VN
1已证明5 '-三磷酸腺苷（ATP）可诱导与发热有关的细胞因子的释放，包括白细胞介素（IL）-1 β、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、吡哆醛-5 ′磷酸-6-偶氮苯基-2 ′，4 ′-二磺酸（PPADS）和亮蓝G（BBG）对体温变化和IL-1 β、IL-6、IL-10、IL-11 β和IL-12的血浆水平增加的影响，研究了ATP介导的嘌呤能信号传导在全身性炎症期间发热和细胞因子释放中的作用。和TNF α诱导的细菌脂多糖（LPS）。2 LPS（大肠杆菌; 50 μ g/kg）引起的发热反应被苏拉明减弱（25 mg/kg和100 mg/kg），PPADS（25 mg kg（-1）），以及选择性更强的P2 X（7）受体拮抗剂BBG（100 mg kg（-1））。3 IL-1 β和IL-6的血浆浓度增加，PPADS（25 μ g kg-1）和BBG（100 mg kg-1）可降低LPS处理后1 h的细胞凋亡率。LPS诱导的血浆TNF-α浓度升高也被BBG（100 mg kg（-1））显著减弱，但PPADS（25 mg kg（-1））没有减弱。4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，ATP通过P2 X（7）受体诱导释放致热细胞因子介导全身炎症过程中的发热。
1 Adenosine 5'-triphosphate (ATP) has been shown to induce release of cytokines implicated in fever, including interleukin(IL)-1 beta, 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-1 beta, IL-6, and TNF alpha induced by bacterial lipopolysaccharide (LPS) in rats.2 LPS (Escherichia coli; 50 mu g 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.3 The increase in plasma concentrations of IL-1 beta and IL-6, measured 1 h after LPS treatment, was reduced by PPADS (25 mu g 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)).4 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.