Circulating monocytes play an important role in acute alcohol induced immunosuppression and chronic alcohol-related liver injury due to their response to increased endotoxin (LPS) during infections and in the serum of alcoholic hepatitis patients (9). In this study, we investigated the effects of acute (short-term) and chronic (prolonged) alcohol exposure of human monocytes using an in vitro system developed to maintain physiologically relevant (25 mM) alcohol concentrations over a period of 7 days in culture. Fig. 1A shows that acute alcohol exposure (1–2 days) decreases LPS-induced TNF-α production. However, extended exposure to alcohol for 4 –7 days (chronic) resulted in significantly increased LPS-induced TNF-α production in human monocytes. Changes in TNF-α protein levels correlated with TNF-α mRNA levels wherein initial alcohol exposure for 3 h to 1 day decreased LPS-induced TNF-α mRNA and 4 –7 days of alcohol exposure exhibited increased LPS-induced TNF-α mRNA (Fig. 1B) in human monocytes. These results indicate that alcohol exposure of monocytes induces hyporesponsiveness to LPS in the initial phase (acute) whereas prolonged (chronic) alcohol exposure sensitizes monocytes to LPS-induced cytokine production regulated at the transcriptional and translational level.
