decreases IRAK-M expression and increases IRAK-1 kinase activity without changes in CD14 and TLR4 expression. This is consistent with studies where monocytes from patients with advanced cirrhosis showed that up-regulation of TNF-α production was due to increased IRAK kinase, increased NFκB activity, and less IκBα protein levels, a lack of IRAK-M induction, and decreased TLR4 expression (45). Previous studies in monocytes have shown that IFN-γ and granulocyte/monocyte CSF can prevent or reverse decreased responses to LPS by inhibition of IRAK kinase degradation and promoting its association to MyD88 without any effect on IRAK kinase activity (46). Considering that chronic alcohol exposure of human monocytes resulted in increased IRAK-1 kinase activity and up-regulation of IKK kinase activity leading to augmentation of LPS-induced NFκB binding and TNF-α expression in our experiments, it cannot be ruled out that chronic alcohol increases IFN-γ production by circulating T and NK cells in vivo to influence this hyperactivity of monocytes and increased inflammation. This possibility awaits further investigation. However, in our experiments, chronic alcohol alone exhibited inhibition of IRAK-M at the mRNA and protein level in monocytes even in the absence of other cell types. Recent studies show that using a human monocytic cell line Mono
