In summary, our studies indicate that alcohol-mediated regulation of IRAK-M, a negative regulator of LPS signaling expressed in monocytes, may be responsible for the switch from a LPS hyporesponsiveness after acute alcohol exposure to reprogramming to increased TNF-α gene expression after chronic alcohol exposure. Thus, it is evident from these studies that the length of alcohol exposure and the resulting immune phenotype of peripheral blood monocytes could set the stage for increased susceptibility to infections or contribution to alcoholic liver injury.
