(38). Increased IRAK-M levels were accompanied by decreased LPS-induced IRAK-1 (17) and IKK kinase activity and decreased NFκB binding along with IκBα degradation. Acute alcohol exposure not only decreased NFκB DNA binding but also reduced its transactivation potential. This is in agreement with previous data showing that acute alcohol promotes DNA binding of the NF-κB p50/p50 homodimer that has minimal transactivational capacity (39). NFκB dimers are released from their complex with IκB proteins followed by their translocation to the nucleus. Although acute alcohol reduced NFκB binding activity with ongoing IκBα degradation, IRAK-1 and IKK kinase activity were suppressed by acute alcohol in monocytes. Our earlier results also show that acute alcohol exposure affects NFκB p65 phosphorylation via modulation of IKK kinase to result in altered NFκB binding and TNF-α expression (20) in human monocytes. Conflicting reports show either a down-regulation or no change in ERK, JNK, and p38 MAPK activity during LPS hyporesponsiveness in macrophages (40, 41). In our experiments, acute alcohol selectively reduced ERK MAPK levels with no significant effect on JNK and p38 MAPK. Our results overall indicate that, similar to the in vivo effects of acute alcohol on Kupffer cells (32), short-term alcohol exposure induces an “LPS
