In contrast to the inhibitory effects of acute alcohol treatment (up to 24 hours), prolonged exposure of human (men and women) peripheral blood monocytes to 25mM ethanol for 7 days increased LPS-induced TNF-α production without affecting IL-10 production (Pang, Bala et al. 2011). Prolonged exposure of Mono Mac 6 cell line to 25mM, 50mM and 75mM ethanol for 7 days also reverses the initial inhibition of LPS or PMA-induced TNF-α production in a dose-dependent manner (Zhang, Bagby et al. 2001). Studies using the RAW 264.7 macrophage cell line and peripheral blood monocytes isolated from healthy men and women demonstrated that this switch to a pro-inflammatory response occurs via decreasing IRAK-M and increasing IRAK-1 and IKK expression resulting in increased phosphorylation of the NFκB p65 subunit, increased NFκB translocation to the nucleus and greater TNF-α production in response to LPS stimulation (Mandrekar, Bala et al. 2009).