Toll-like receptors 2 and 4: initiators of non-septic inflammation in critical care medicine?
Toll-like receptors 2 and 4: initiators of non-septic inflammation in critical care medicine?
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DOI：
10.1007/s00134-010-1983-5
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发表时间：
2010-11
影响因子：
38.9
通讯作者：
Abraham, Edward
中科院分区：
文献类型：
--
作者：
Lorne, Emmanuel;Dupont, Herve;Abraham, Edward
尽管Toll样受体（TLR）在细菌感染和脓毒症中的作用已得到充分表征，但最近的研究还表明，在LPS或其他细菌产物不存在的情况下，TLR 4和TLR 2可在促成急性炎症过程和器官功能障碍中发挥重要作用。这篇综述不仅提出了对导致器官功能障碍和危重病结局的病理生理机制的见解，而且还提出了改善此类TLR介导的反应的直接治疗方法，这些方法可能对危重病患者具有临床益处。使用PubMed检索，对TLR 4和TLR 2在与重症监护医学相关的无菌性炎症中的作用进行文献综述，包括1990年至2010年的英文原创论文。越来越多的证据表明，TLR 4和TLR 2不仅是细菌产物的受体，而且还可以通过与危重疾病的病理生理学相关的其他机制被激活。有证据表明，TLR 4和TLR 2参与局部缺血-再灌注损伤和创伤，其中在循环或局部器官部位如肺中检测不到革兰氏阴性或革兰氏阳性细菌。在这些情况下，TLR可以抑制其他促炎信号，从而促进细胞活化，导致急性肺损伤和其他器官系统功能障碍。通过活性氧（ROS）、热休克蛋白和其他非LPS依赖性机制激活TLR 4和TLR 2的结果可能不同于与细菌的膜组分与TLR 4或TLR 2的结合相关的结果，并且可能产生不同的基因激活和促炎介质释放特征。
Although the role of Toll-like receptors (TLRs) in bacterial infection and sepsis is well characterized, recent studies have also shown that TLR4 and TLR2 can play an important role in contributing to acute inflammatory processes and organ dysfunction in settings in which LPS or other bacterial products are not present. This review presents not only insights into pathophysiologic mechanisms that contribute to organ dysfunction and outcome in critical illness, but also direct therapeutic approaches to ameliorating such TLR-mediated responses that may potentially be of clinical benefit in critically ill patients. Literature review of the role of TLR4 and TLR2 in sterile inflammation relevant to critical care medicine using PubMed search, including original papers in English from 1990 to 2010. There is increasing evidence that TLR4 and TLR2 are not only receptors for bacterial products, but also can be activated through other mechanisms relevant to the pathophysiology of critical illnesses. There is evidence that TLR4 and TLR2 are involved in ischemia-reperfusion injury and trauma where Gram-negative or Gram-positive bacteria are not detectible in the circulation or local organ sites, such as the lungs. In these settings TLRs can transduce other proinflammatory signals and thereby contribute to cellular activation leading to acute lung injury and other organ system dysfunction. The consequences of TLR4 and TLR2 activation through reactive oxygen species (ROS), heat shock proteins, and other non-LPS dependent mechanisms may be different from those associated with binding of the membrane component of bacteria to TLR4 or TLR2 and may produce different signatures of gene activation and release of proinflammatory mediators.
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