Several studies have shown a dose-dependent effect of alcohol on the LPS response by monocytes/macrophages. Pre-incubation of human monocytes isolated from healthy men and women in vitro with 25mM alcohol [~0.1g/dL blood alcohol concentration (BAC)] for 24 hours inhibits nuclear translocation of NFκB in response to LPS, and thereby production of pro-inflammatory cytokines (Muralidharan, Ambade et al. 2014). In vitro exposure of the macrophage cell line RAW 264.7 and human peripheral blood monocytes to 25mM ethanol for 24 hours followed by stimulation of LPS also leads to decreased TNF-α production by increasing the expression of IL-1R-associated kinase-monocyte (IRAK-M), a negative regulator of LPS signaling (Mandrekar, Bala et al. 2009). Similarly, exposure of the human monocytic cell line mono Mac 6 cells to 25mM, 50mM, or 75mM ethanol for 24 hours inhibited LPS and phorbol myristate acetate-(PMA) induced TNF-α production in a dose-dependent manner (Zhang, Bagby et al. 2001). This inhibitory effect on NFκB activity is partly due to the increased proteolytic degradation of IκBα kinase (IKK) and consequent decreased phosphorylation of the NFκB p65 subunit (Mandrekar, Jeliazkova et al. 2007).
