Abstract
Endotoxin tolerance was first described in a study that exposed animals to a sublethal dose of bacterial endotoxin. The animals subsequently survived a lethal injection of endotoxin. This refractory state is associated with the innate immune system and, in particular, with monocytes and macrophages, which act as the main participants. Several mechanisms are involved in the control of endotoxin tolerance; however, a full understanding of this phenomenon remains elusive. A number of recent reports indicate that clinical examples of endotoxin tolerance include not only sepsis but also diseases such as cystic fibrosis and acute coronary syndrome. In these pathologies, the risk of new infections correlates with a refractory state. This review integrates the molecular basis and clinical implications of endotoxin tolerance in various pathologies.
Highlights
The mammalian innate immune system (IIS) is able to detect and respond to danger signals from various sources such as bacteria, tumor processes, and tissue damage [1]
We reviewed the role of interleukin-1 receptor-associated kinase (IRAK)-M in endotoxin tolerance (ET) in detail in an earlier study [52]
This complex pathology results from a deregulated inflammatory response by the IIS following a systemic bacterial infection
Summary
The mammalian innate immune system (IIS) is able to detect and respond to danger signals from various sources such as bacteria, tumor processes, and tissue damage [1]. Data from a study that used this type of model indicated that only 1 hour of LPS exposure was required to induce an ET This refractory state is not permanent, and after 5 days, the cells reverted to a proinflammatory phenotype in response to endotoxin stimulation [17]. Sepsis: where endotoxin tolerance was first described A clinically relevant example of ET was observed in patients with sepsis [59] This complex pathology results from a deregulated inflammatory response by the IIS following a systemic bacterial infection. Despite the absence of any previous infection, the MΦs showed a diminished response ex vivo to a subsequent endotoxin challenge in addition to other main characteristics of an ET status (for example, low expression of MHC-II and poor antigen presentation). All of these findings suggest that those diverse pathological contexts that generate a regulation IIS response might be revisited under the light of a putative tolerant process
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