[Progress of the study on endotoxin tolerance mechanisms]

Endotoxin tolerance has been attracted for more than 50 years, but so far its molecular mechanisms remain to be resolved. TLR4, the major receptor for LPS, was found to be involved in LPS signaling transduction and to have a close relationship with endotoxin tolerance. Quantitative, structural and functional changes of receptors, adaptor proteins and transcription factors in TLR4 signaling pathways might have effects on the decrease in proinflammatory cytokines, increase in anti-inflammatory cytokines and activation of special signaling pathways (such as PI3K pathways) as well as some negative regulation factors (SHIP1,SOCS, FLN29, et al) during the development of endotoxin tolerance. Furthermore, TLR2, Gi protein, PKC and several selective splicing isoforms are involved in endotoxin tolerance. So endotoxin tolerance is a complicated pathophysiological process caused by diverse reasons and involved in many biological substances. It is also an important protective mechanism of human body infected with G- bacteria. Exploring the mechanism of endotoxin tolerance, seeking endogenous protective mechanism of human body would provide new theory and new ways to overcome series of fatal infective diseases including sepsis.