Ethanol can increase proinflammatory cytokine levels in the blood by activating proinflammatory responses in the liver and other tissues. One mechanism seems to involve the ethanol-induced increase in gut permeability (or “leakiness”) mentioned above (Ferrier et al. 2006). At high doses (at least 2 to 3 g/kg ethanol administered into the stomach), ethanol potentiates innate immune signaling in the gut (Ferrier et al. 2006). This disrupts the connections between the cells lining the gut (i.e., gut tight junctions) and opens sites that allow gut bacteria and their endotoxins to enter the blood vessels leading to the liver, where they can initiate a proinflammatory response (Sims et al. 2010). Thus, high doses of ethanol increase systemic proinflammatory responses, which can then spread to the brain through TNF-α and likely other cytokines (see figure 6).
