These studies propose that this phenomenon can be considered another form of alternative activation triggered by bacterial signatures such as lipopolysaccharides. We and other authors have shown that tolerant human Ifenprodil hemitartrate monocytes are characterized by rapid IRAK-M overexpression, high levels of CD163 and low HLA expression. In-depth studies of ET development in gene-deficient mice analyzed the participation of intracellular molecules in this process and established the roles of SHIP-1, A20 and IRAK-M. This pseudokinase could be considered a ����master regulator���� of ET because it is consistently induced into ET and is implicated in human pathologies in which ET is manifest, such as sepsis, cancer, ACS and asthma. In a human in vitro ET model, rapid IRAK-M up-regulation was described and is expressed in freshly isolated sepsis monocytes. More importantly, IRAK-M up-regulation was associated with high mortality after Gram-negative-induced sepsis. One of the illnesses in which ET takes place is acute coronary syndrome. ACS includes a range of thrombotic coronary artery diseases, such as unstable angina, ST-elevation SB 611812 myocardial infarction and non-ST-elevation myocardial infarction. The innate immune system plays a key role in the progression of atherosclerotic lesions and in remodeling after myocardial infarction. In this context, the activation of the innate immune response mediated by MWs releases factors that cause inflammation, tissue damage and plaque instability. We have previously reported that the monocytes of ACS patients show a pro-inflammatory phenotype after 1�C3 h of MI, with up-regulation of TNF-a. These cells have high levels of IRAK-M, thus providing negative feedback regulation for the pro-inflammatory response. This is a classic paradigm of ET producing a hyporesponsive state following an LPS challenge. These data suggest a potential switch from a pro-inflammatory phenotype or M1 to a tolerant state that matches an M2 phenotype in these cells. The absence of previous infections in these patients suggested the existence of ����damps���� that trigger a tolerant state. Several internal factors could act as initial stimuli in this respect; molecules known as Danger Associated Molecular Patterns are candidates, such as hyaluronic acid, High Mobility Group B1 and HSP. Moreover, due to the breakdown of tissue during MI, other DAMPs could spread, such as those from mitochondria.