alcohol affects the expression of microglial cell surface receptors. Acute alcohol administration induces Toll-like receptor (TLR)4/type I interleukin (IL)-1 receptor signaling mediators: nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen activated protein kinase signal transduction cascades (Blanco et al. 2005). In contrast, alcohol impairs microglial activation in TLR4 null mice (Fernandez-Lizarbe et al. 2009). Although the literature on TNF-α expression is varied (Nelson et al. 1990; Nair et al. 1994; Avogaro et al. 2003), the most recent study indicates that alcohol increases brain TNF-α expression (Qin et al. 2008), which may be neuroprotective; indeed, low concentrations of TNF-α (20 ng/ml) in slice cultures synergize neurotoxicity by impairing EAAT2/GLT-1-mediated glutamate reuptake (Zou et al. 2005). Butylated hydroxytoluene, an antioxidant, reverses this inhibition and blocks the nuclear translocation of the NF-κB subunit p65 (Zou et al. 2005). Finally, in abstinent alcoholics, etanercept (a soluble TNF-α receptor antibody with demonstrated efficacy in the treatment of autoimmune disorders) reduces rapid eye movement sleep, a prognostic indicator for future alcohol relapse (Irwin et al. 2009).
