Endotoxin tolerance and the immune system

Abstract

Endotoxin tolerance is a phenomenon known to cause innate immune cells, like macrophages, to produce a decreased pro-inflammatory response to a pathogen associated molecular pattern (PAMP), like LPS, after pre-stimulation. Innate immune cells involved have thought to be primarily monocytes/macrophages but evidence has been found for involvement of dendritic cells, neutrophils and T cells. The molecular mechanisms of endotoxin tolerance are vague. However, negative regulators such as SOCS1, IRAK-M and SHIP are believed to play a large role, along with the down-regulation of TLR4 on cell surface and gene re-programming. Clinically, sepsis is a major model of endotoxin tolerance due to the immunosuppression observed; however, new applications for endotoxin tolerance in pathology are becoming apparent, including ischemia-reperfusion injury. Little is known about cross-tolerance, but it does seem to have similarities and differences to homo-tolerance and also application into the clinical world. This review provides an overall picture of findings within endotoxin tolerance from the beginning to recent, including cellular and molecular mechanisms along with clinical applications.