Abstract
BACKGROUND: Alcohol consumption modulates immune function, in part by promoting microbial translocation. This process is thought to trigger an acute-phase immune response, contributing to alcohol-related immune modulation. However, most evidence on these effects arises from preclinical models. Additionally, existing human studies lack a placebo control, rely on a single alcohol dose, or fail to account for individual drinking history. METHODS: This study examined in vivo concentrations of lipopolysaccharide (LPS, a marker of microbial translocation), acute-phase proteins, cytokines, and chemokines under low-dose alcohol, moderate-dose alcohol, and placebo using a within-subjects design in light and heavy drinkers. Participants (N = 32) were light drinkers (n = 15) and nontreatment-seeking heavy drinkers (n = 17). Groups did not differ on demographics. Participants received each dose condition in randomized order. Blood samples were collected at baseline and at hourly intervals for 4 h. Plasma concentrations of LPS, acute-phase proteins (LPS binding protein [LBP], soluble cluster of differentiation 14 [sCD14], and soluble cluster of differentiation 163 [sCD163]), and cytokines/chemokines (interleukin 6 [IL-6], interleukin 8 [IL-8], interleukin 10 [IL-10], monocyte chemoattractant protein [MCP-1], and tumor necrosis factor alpha [TNF-α]) were quantified using immunoassays. Linear mixed models tested effects of dose condition, drinker group, time, and the three-way interaction. Further analyses tested associations of LPS, LBP, sCD14, and sCD163 with cytokines/chemokines. RESULTS: The three-way interaction of dose by group by time was significant for IL-6 (p = 0.042), IL-8 (p = 0.039), MCP-1 (p = 0.001), and TNF-α (p = 0.001). LPS was associated with concentrations of interleukins. Levels of sCD163 were 43% higher in heavy drinkers overall. Heavy drinkers exhibited apparent conditioned peripheral immune suppression, wherein the expectation of alcohol elicited selective immunosuppressive responses. CONCLUSIONS: This study offers novel in vivo evidence that alcohol-induced changes in immune function are dependent on both acute dose and chronic drinking behavior.