The influence of acute and chronic alcohol exposure on innate immune cells from peripheral blood monocytes to tissue macrophages originating from spleen, lungs, and liver can be diverse. Earlier studies have shown that sterilization of the gut with antibiotics abrogated the in vivo effects of acute alcohol on Kupffer cells, indicating that circulating endotoxin played a key role in the effects of alcohol (32). Furthermore, in vivo acute alcohol exposure of murine Kupffer cells show decreased responsiveness to LPS, and this has been related to decreased IRAK expression, reduced NFκB activity (33), and decreased intracellular Ca2+ concentration (32). Subsequent studies also revealed that acute in vivo ethanol exposure of Kupffer cells increased CD14 expression through a mechanism dependent on AP-1 activation (34). In addition, splenic and alveolar macrophages exposed to a single dose of in vivo alcohol followed by ex vivo stimulation of LPS showed a significant decrease in proinflammatory responses and impaired phagocytic function, likely due to inhibition of pattern recognition receptors and down-stream MAPK (36). In our studies, acute alcohol did not affect surface expression of LPS receptors, CD14, and TLR4, whereas LPS-mediated signaling was altered in peripheral blood human monocytes.
