Monnig Mollie A, Lamb Philip S, Clark Samantha E, Monti Peter M
Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA.
Alcohol Clin Exp Res (Hoboken). 2025 Aug;49(8):1644-1658. doi: 10.1111/acer.70106. Epub 2025 Jun 30.
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.
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.
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.
This study offers novel in vivo evidence that alcohol-induced changes in immune function are dependent on both acute dose and chronic drinking behavior.
饮酒会调节免疫功能，部分原因是促进微生物易位。这一过程被认为会引发急性期免疫反应，导致与酒精相关的免疫调节。然而，关于这些影响的大多数证据来自临床前模型。此外，现有的人体研究缺乏安慰剂对照，依赖单一酒精剂量，或未考虑个体饮酒史。
本研究采用受试者内设计，在轻度饮酒者和重度饮酒者中，检测低剂量酒精、中度剂量酒精和安慰剂条件下体内脂多糖（LPS，微生物易位的标志物）、急性期蛋白、细胞因子和趋化因子的浓度。参与者（N = 32）为轻度饮酒者（n = 15）和未寻求治疗的重度饮酒者（n = 17）。两组在人口统计学特征上无差异。参与者按随机顺序接受每种剂量条件。在基线和每小时采集一次血样，共采集4小时。使用免疫测定法定量血浆中LPS、急性期蛋白（LPS结合蛋白[LBP]、可溶性分化簇14[sCD14]和可溶性分化簇163[sCD163]）以及细胞因子/趋化因子（白细胞介素6[IL-6]、白细胞介素8[IL-8]、白细胞介素10[IL-10]、单核细胞趋化蛋白[MCP-1]和肿瘤坏死因子α[TNF-α]）的浓度。线性混合模型测试剂量条件、饮酒者组、时间以及三者交互作用的影响。进一步分析测试LPS、LBP、sCD14和sCD163与细胞因子/趋化因子的关联。
IL-6（p = 0.042）、IL-8（p = 0.039）、MCP-1（p = 0.001）和TNF-α（p = 0.001）的剂量×组×时间三者交互作用显著。LPS与白细胞介素浓度相关。总体而言，重度饮酒者的sCD163水平高43%。重度饮酒者表现出明显的条件性外周免疫抑制，即对酒精的预期引发选择性免疫抑制反应。
本研究提供了新的体内证据，表明酒精引起的免疫功能变化既取决于急性剂量，也取决于慢性饮酒行为。
