Ethanol suppresses cytokine responses induced through Toll-like receptors as well as innate resistance to Escherichia coli in a mouse model for binge drinking.

Toll-like receptors (TLRs) recognize molecular patterns associated with pathogens and initiate various mechanisms that are critical in innate resistance to infection. It has been reported that acute administration of ethanol suppresses responses mediated through TLR3 and TLR4. However, it is not known whether this is also true for other TLRs. Ligands for TLR2/TLR6 (zymosan A), TLR5 (bacterial flagellin), TLR7 (R-848), and TLR9 (CpG DNA) were used to induce cytokine production in mice, and the effects of ethanol (6 g/kg by gavage) on this induction were determined. Because different cell types may be affected differently by ethanol, cytokines were measured in serum (as an indication of cytokines produced by a number of different cell types) and in peritoneal lavage fluid (as an indicator of cytokine production primarily by peritoneal macrophages). Ethanol significantly affected the concentration of at least one of the cytokines evaluated in serum or peritoneal lavage fluid [interleukin (IL)-6, IL-10, and IL-12 p40 subunit] induced by all TLR ligands tested. The results also supported the suggestion that serum and peritoneal cytokines were mostly derived from different cells types, which were affected differently by ethanol. To determine whether ethanol-induced changes in TLR responses were associated with suppression of innate resistance to infection, a model of experimental peritonitis with a nonpathogenic (indigenous) strain of Escherichia coli was developed. Ethanol significantly decreased host resistance to E. coli peritonitis. Thus, ethanol suppresses responses induced by TLR receptors in mice and in the same experimental system it suppresses resistance to infection.