Ethanol modulates the function of monocytes, immature innate immune cells that circulate in the blood until recruited into tissues, in a dose and time dependent manner. Monocytes express Toll-like receptor (TLR) 4, which is the PRR responsible for recognizing the endotoxin LPS on the surface of Gram negative bacteria. Upon LPS binding, monocytes become activated, mature into macrophages and migrate into tissues where they respond to infection by secreting various cytokines, recruiting additional leukocytes via production of chemokines and presenting pathogen-derived peptides to T cells to activate them. These events depend on the activation of the nuclear factor kappa B (NFκB) heterodimer p50–p65 and its translocation to the nucleus leading to the expression and production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-12, and tumor necrosis factor (TNF)-α (Hoffmann, Natoli et al. 2006, Janeway 2008). Often, investigators stimulate with LPS after pre-exposure to ethanol to mimic inflammation observed in trauma patients with high blood alcohol levels and explore the alterations in immunity that lead to frequent subsequent infections among this group.
