Toll-like receptors 2 and 4: initiators of non-septic inflammation in critical care medicine?
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Lorne
Emmanuel
E
Pole Anesthésie Réanimation, Centre Hospitalier Universitaire d'Amiens, Université Jules Verne de Picardie, Place Victor Pauchet, 80054, Amiens Cedex, France. lorne.emmanuel@chu-amiens.fr
Dupont
Hervé
H
Abraham
Edward
E
D003422:Critical Care / Q000379:methods; D016638:Critical Illness; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism
D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4